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Substance Use in Pregnancy
Jeffrey DeVido MD MTS
UCSF Assistant Clinical Professor Department of Psychiatry
Medical Director Marin County Drug Medi-Cal Program
1st Annual Bay Area Maternal Mental Health Conference 10 September 2016 130-230pm
Disclaimer
I have no relevant conflicts of interest to
declare
Aim of this presentation bull Review of Addictions and Epidemiology of addictions in women
bull Alcohol Use Disorders in Pregnancy
ndash Understands fetal malformation risks
ndash Describe MAT options
ndash Risks of alcohol withdrawal and risks of benzodiazepines in pregnancy
bull Opioid Use Disorders in Pregnancy
ndash Maternal and fetal risks
ndash Screening tools
ndash Describe MAT options and risks fetalmaternalbreastfeeding
bull Amphetamine Use Disorders in Pregnancy
From ldquoThis Tennessee Law About Pregnant Addicts Wonrsquot Make Them Stop Using Drugsrdquo Mommyish Mon July 14th 2014 Available on httpwwwmommyishcom20140714pregnancy-law-criminalizes-drug-use
What is Addiction
bull Addiction is a chronic progressive behavioral
disorder whose central feature is compulsive drug
use despite adverse consequences
bull Not the same as physiologic dependence (tolerance
and withdrawal)
bull ldquoAddictionrdquo = Substance Use Disorder
bull Gender Differences in Substance Use Disorders decreasing (Keyes 2008)
bull Telescoping (Randall 1999)
bull When present for treatment report greater impairment relative to men in employment social psychiatric and medical domains (Hernandez-Avila et al 2004)
bull More likely to use substances than men to manage negative affects (Saladin et al 2012)
bull Less than 20 of those women who need treatment receive it yearly (Terplan et al 2012)
bull Women less likely to engage in treatment than men (Back et al 2010) bull Among pregnant women perception of risk is important predictor of use (Blume
et al 2007)
Epidemiology of Addiction in Reproductive Age Women
Prevalence of Illicit Substance Cigarette and Alcohol Use in Pregnant Women
Laura P McLafferty Madeleine Becker Nehama Dresner Samantha Meltzer-Brody Priya Gopalan Jody Glance Guitelle St
Victor Leena Mittal Patrick Marshalek Laura Lander Linda LM Worley
Guidelines for the Management of Pregnant Women With Substance Use Disorders
Psychosomatics Volume 57 Issue 2 2016 115ndash130
httpdxdoiorg101016jpsym201512001
Epidemiology of Addiction in Pregnant Women
Epidemiology of Addiction in Pregnant Women
bull Women generally decrease use during pregnancy bull Danish study 90 of women reduced intake of
EtOH upon learning of pregnancy (Kesmodel et al 2003)
bull NSDUH 2010
Pregnant () Not Pregnant ()
Current EtOH Use 108 547
Binge Drinking 37 246
Heavy Drinking 1 54
Alcohol Use Disorders and Pregnancy
Hogarthrsquos Gin Lane (1751)
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
hellipmore historical notes
bull Paul Lemoine 1967 characterized alcohol as
teratogen
bull Kenneth Lyon Jones 1973 (dysmorphologist)
coined term fetal alcohol syndrome (typically
14 or more drinks daily)
What we know Risk of alcohol
bull Not controversial excessive alcohol use (gt2 units per
day or gt4 units per sitting) DOSE RESPONSE
ndash Increased risk of miscarriage reduction in fetal growth
impaired neurodevelopment (American Academy of
Pediatrics 2000) low birth weight (Patra 2011)
ndash Preterm birth (Albertsen et al 2004)
ndash Dose response effect on FAS (Rehm 2010)
ndash Withdrawal in infant
What we know Risk of alcohol
bull Controversial
ndash Mixed evidence that low-levels of drinking pose risk
to fetus or mother (NICE March 2008) but no
consensus on what ldquolow levelrdquo is
ndash Several countries have wrestled with how to advise
pregnant women on alcohol use Australia Denmark
American Academy of Pediatrics November 2015
bull During pregnancy
ndash no amount of alcohol intake should be considered safe
ndash there is no safe trimester to drink alcohol
ndash all forms of alcohol such as beer wine and liquor pose
similar risk and
ndash binge drinking poses dose-related risk to the developing
fetus
(Williams et al 2015)
MAT for AUD in Pregnancy
bull Disulfiram (Antabuse)
bull Naltrexone (Revia Vivitrol)
bull Acamprosate (Campral)
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Disclaimer
I have no relevant conflicts of interest to
declare
Aim of this presentation bull Review of Addictions and Epidemiology of addictions in women
bull Alcohol Use Disorders in Pregnancy
ndash Understands fetal malformation risks
ndash Describe MAT options
ndash Risks of alcohol withdrawal and risks of benzodiazepines in pregnancy
bull Opioid Use Disorders in Pregnancy
ndash Maternal and fetal risks
ndash Screening tools
ndash Describe MAT options and risks fetalmaternalbreastfeeding
bull Amphetamine Use Disorders in Pregnancy
From ldquoThis Tennessee Law About Pregnant Addicts Wonrsquot Make Them Stop Using Drugsrdquo Mommyish Mon July 14th 2014 Available on httpwwwmommyishcom20140714pregnancy-law-criminalizes-drug-use
What is Addiction
bull Addiction is a chronic progressive behavioral
disorder whose central feature is compulsive drug
use despite adverse consequences
bull Not the same as physiologic dependence (tolerance
and withdrawal)
bull ldquoAddictionrdquo = Substance Use Disorder
bull Gender Differences in Substance Use Disorders decreasing (Keyes 2008)
bull Telescoping (Randall 1999)
bull When present for treatment report greater impairment relative to men in employment social psychiatric and medical domains (Hernandez-Avila et al 2004)
bull More likely to use substances than men to manage negative affects (Saladin et al 2012)
bull Less than 20 of those women who need treatment receive it yearly (Terplan et al 2012)
bull Women less likely to engage in treatment than men (Back et al 2010) bull Among pregnant women perception of risk is important predictor of use (Blume
et al 2007)
Epidemiology of Addiction in Reproductive Age Women
Prevalence of Illicit Substance Cigarette and Alcohol Use in Pregnant Women
Laura P McLafferty Madeleine Becker Nehama Dresner Samantha Meltzer-Brody Priya Gopalan Jody Glance Guitelle St
Victor Leena Mittal Patrick Marshalek Laura Lander Linda LM Worley
Guidelines for the Management of Pregnant Women With Substance Use Disorders
Psychosomatics Volume 57 Issue 2 2016 115ndash130
httpdxdoiorg101016jpsym201512001
Epidemiology of Addiction in Pregnant Women
Epidemiology of Addiction in Pregnant Women
bull Women generally decrease use during pregnancy bull Danish study 90 of women reduced intake of
EtOH upon learning of pregnancy (Kesmodel et al 2003)
bull NSDUH 2010
Pregnant () Not Pregnant ()
Current EtOH Use 108 547
Binge Drinking 37 246
Heavy Drinking 1 54
Alcohol Use Disorders and Pregnancy
Hogarthrsquos Gin Lane (1751)
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
hellipmore historical notes
bull Paul Lemoine 1967 characterized alcohol as
teratogen
bull Kenneth Lyon Jones 1973 (dysmorphologist)
coined term fetal alcohol syndrome (typically
14 or more drinks daily)
What we know Risk of alcohol
bull Not controversial excessive alcohol use (gt2 units per
day or gt4 units per sitting) DOSE RESPONSE
ndash Increased risk of miscarriage reduction in fetal growth
impaired neurodevelopment (American Academy of
Pediatrics 2000) low birth weight (Patra 2011)
ndash Preterm birth (Albertsen et al 2004)
ndash Dose response effect on FAS (Rehm 2010)
ndash Withdrawal in infant
What we know Risk of alcohol
bull Controversial
ndash Mixed evidence that low-levels of drinking pose risk
to fetus or mother (NICE March 2008) but no
consensus on what ldquolow levelrdquo is
ndash Several countries have wrestled with how to advise
pregnant women on alcohol use Australia Denmark
American Academy of Pediatrics November 2015
bull During pregnancy
ndash no amount of alcohol intake should be considered safe
ndash there is no safe trimester to drink alcohol
ndash all forms of alcohol such as beer wine and liquor pose
similar risk and
ndash binge drinking poses dose-related risk to the developing
fetus
(Williams et al 2015)
MAT for AUD in Pregnancy
bull Disulfiram (Antabuse)
bull Naltrexone (Revia Vivitrol)
bull Acamprosate (Campral)
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Aim of this presentation bull Review of Addictions and Epidemiology of addictions in women
bull Alcohol Use Disorders in Pregnancy
ndash Understands fetal malformation risks
ndash Describe MAT options
ndash Risks of alcohol withdrawal and risks of benzodiazepines in pregnancy
bull Opioid Use Disorders in Pregnancy
ndash Maternal and fetal risks
ndash Screening tools
ndash Describe MAT options and risks fetalmaternalbreastfeeding
bull Amphetamine Use Disorders in Pregnancy
From ldquoThis Tennessee Law About Pregnant Addicts Wonrsquot Make Them Stop Using Drugsrdquo Mommyish Mon July 14th 2014 Available on httpwwwmommyishcom20140714pregnancy-law-criminalizes-drug-use
What is Addiction
bull Addiction is a chronic progressive behavioral
disorder whose central feature is compulsive drug
use despite adverse consequences
bull Not the same as physiologic dependence (tolerance
and withdrawal)
bull ldquoAddictionrdquo = Substance Use Disorder
bull Gender Differences in Substance Use Disorders decreasing (Keyes 2008)
bull Telescoping (Randall 1999)
bull When present for treatment report greater impairment relative to men in employment social psychiatric and medical domains (Hernandez-Avila et al 2004)
bull More likely to use substances than men to manage negative affects (Saladin et al 2012)
bull Less than 20 of those women who need treatment receive it yearly (Terplan et al 2012)
bull Women less likely to engage in treatment than men (Back et al 2010) bull Among pregnant women perception of risk is important predictor of use (Blume
et al 2007)
Epidemiology of Addiction in Reproductive Age Women
Prevalence of Illicit Substance Cigarette and Alcohol Use in Pregnant Women
Laura P McLafferty Madeleine Becker Nehama Dresner Samantha Meltzer-Brody Priya Gopalan Jody Glance Guitelle St
Victor Leena Mittal Patrick Marshalek Laura Lander Linda LM Worley
Guidelines for the Management of Pregnant Women With Substance Use Disorders
Psychosomatics Volume 57 Issue 2 2016 115ndash130
httpdxdoiorg101016jpsym201512001
Epidemiology of Addiction in Pregnant Women
Epidemiology of Addiction in Pregnant Women
bull Women generally decrease use during pregnancy bull Danish study 90 of women reduced intake of
EtOH upon learning of pregnancy (Kesmodel et al 2003)
bull NSDUH 2010
Pregnant () Not Pregnant ()
Current EtOH Use 108 547
Binge Drinking 37 246
Heavy Drinking 1 54
Alcohol Use Disorders and Pregnancy
Hogarthrsquos Gin Lane (1751)
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
hellipmore historical notes
bull Paul Lemoine 1967 characterized alcohol as
teratogen
bull Kenneth Lyon Jones 1973 (dysmorphologist)
coined term fetal alcohol syndrome (typically
14 or more drinks daily)
What we know Risk of alcohol
bull Not controversial excessive alcohol use (gt2 units per
day or gt4 units per sitting) DOSE RESPONSE
ndash Increased risk of miscarriage reduction in fetal growth
impaired neurodevelopment (American Academy of
Pediatrics 2000) low birth weight (Patra 2011)
ndash Preterm birth (Albertsen et al 2004)
ndash Dose response effect on FAS (Rehm 2010)
ndash Withdrawal in infant
What we know Risk of alcohol
bull Controversial
ndash Mixed evidence that low-levels of drinking pose risk
to fetus or mother (NICE March 2008) but no
consensus on what ldquolow levelrdquo is
ndash Several countries have wrestled with how to advise
pregnant women on alcohol use Australia Denmark
American Academy of Pediatrics November 2015
bull During pregnancy
ndash no amount of alcohol intake should be considered safe
ndash there is no safe trimester to drink alcohol
ndash all forms of alcohol such as beer wine and liquor pose
similar risk and
ndash binge drinking poses dose-related risk to the developing
fetus
(Williams et al 2015)
MAT for AUD in Pregnancy
bull Disulfiram (Antabuse)
bull Naltrexone (Revia Vivitrol)
bull Acamprosate (Campral)
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
From ldquoThis Tennessee Law About Pregnant Addicts Wonrsquot Make Them Stop Using Drugsrdquo Mommyish Mon July 14th 2014 Available on httpwwwmommyishcom20140714pregnancy-law-criminalizes-drug-use
What is Addiction
bull Addiction is a chronic progressive behavioral
disorder whose central feature is compulsive drug
use despite adverse consequences
bull Not the same as physiologic dependence (tolerance
and withdrawal)
bull ldquoAddictionrdquo = Substance Use Disorder
bull Gender Differences in Substance Use Disorders decreasing (Keyes 2008)
bull Telescoping (Randall 1999)
bull When present for treatment report greater impairment relative to men in employment social psychiatric and medical domains (Hernandez-Avila et al 2004)
bull More likely to use substances than men to manage negative affects (Saladin et al 2012)
bull Less than 20 of those women who need treatment receive it yearly (Terplan et al 2012)
bull Women less likely to engage in treatment than men (Back et al 2010) bull Among pregnant women perception of risk is important predictor of use (Blume
et al 2007)
Epidemiology of Addiction in Reproductive Age Women
Prevalence of Illicit Substance Cigarette and Alcohol Use in Pregnant Women
Laura P McLafferty Madeleine Becker Nehama Dresner Samantha Meltzer-Brody Priya Gopalan Jody Glance Guitelle St
Victor Leena Mittal Patrick Marshalek Laura Lander Linda LM Worley
Guidelines for the Management of Pregnant Women With Substance Use Disorders
Psychosomatics Volume 57 Issue 2 2016 115ndash130
httpdxdoiorg101016jpsym201512001
Epidemiology of Addiction in Pregnant Women
Epidemiology of Addiction in Pregnant Women
bull Women generally decrease use during pregnancy bull Danish study 90 of women reduced intake of
EtOH upon learning of pregnancy (Kesmodel et al 2003)
bull NSDUH 2010
Pregnant () Not Pregnant ()
Current EtOH Use 108 547
Binge Drinking 37 246
Heavy Drinking 1 54
Alcohol Use Disorders and Pregnancy
Hogarthrsquos Gin Lane (1751)
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
hellipmore historical notes
bull Paul Lemoine 1967 characterized alcohol as
teratogen
bull Kenneth Lyon Jones 1973 (dysmorphologist)
coined term fetal alcohol syndrome (typically
14 or more drinks daily)
What we know Risk of alcohol
bull Not controversial excessive alcohol use (gt2 units per
day or gt4 units per sitting) DOSE RESPONSE
ndash Increased risk of miscarriage reduction in fetal growth
impaired neurodevelopment (American Academy of
Pediatrics 2000) low birth weight (Patra 2011)
ndash Preterm birth (Albertsen et al 2004)
ndash Dose response effect on FAS (Rehm 2010)
ndash Withdrawal in infant
What we know Risk of alcohol
bull Controversial
ndash Mixed evidence that low-levels of drinking pose risk
to fetus or mother (NICE March 2008) but no
consensus on what ldquolow levelrdquo is
ndash Several countries have wrestled with how to advise
pregnant women on alcohol use Australia Denmark
American Academy of Pediatrics November 2015
bull During pregnancy
ndash no amount of alcohol intake should be considered safe
ndash there is no safe trimester to drink alcohol
ndash all forms of alcohol such as beer wine and liquor pose
similar risk and
ndash binge drinking poses dose-related risk to the developing
fetus
(Williams et al 2015)
MAT for AUD in Pregnancy
bull Disulfiram (Antabuse)
bull Naltrexone (Revia Vivitrol)
bull Acamprosate (Campral)
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
What is Addiction
bull Addiction is a chronic progressive behavioral
disorder whose central feature is compulsive drug
use despite adverse consequences
bull Not the same as physiologic dependence (tolerance
and withdrawal)
bull ldquoAddictionrdquo = Substance Use Disorder
bull Gender Differences in Substance Use Disorders decreasing (Keyes 2008)
bull Telescoping (Randall 1999)
bull When present for treatment report greater impairment relative to men in employment social psychiatric and medical domains (Hernandez-Avila et al 2004)
bull More likely to use substances than men to manage negative affects (Saladin et al 2012)
bull Less than 20 of those women who need treatment receive it yearly (Terplan et al 2012)
bull Women less likely to engage in treatment than men (Back et al 2010) bull Among pregnant women perception of risk is important predictor of use (Blume
et al 2007)
Epidemiology of Addiction in Reproductive Age Women
Prevalence of Illicit Substance Cigarette and Alcohol Use in Pregnant Women
Laura P McLafferty Madeleine Becker Nehama Dresner Samantha Meltzer-Brody Priya Gopalan Jody Glance Guitelle St
Victor Leena Mittal Patrick Marshalek Laura Lander Linda LM Worley
Guidelines for the Management of Pregnant Women With Substance Use Disorders
Psychosomatics Volume 57 Issue 2 2016 115ndash130
httpdxdoiorg101016jpsym201512001
Epidemiology of Addiction in Pregnant Women
Epidemiology of Addiction in Pregnant Women
bull Women generally decrease use during pregnancy bull Danish study 90 of women reduced intake of
EtOH upon learning of pregnancy (Kesmodel et al 2003)
bull NSDUH 2010
Pregnant () Not Pregnant ()
Current EtOH Use 108 547
Binge Drinking 37 246
Heavy Drinking 1 54
Alcohol Use Disorders and Pregnancy
Hogarthrsquos Gin Lane (1751)
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
hellipmore historical notes
bull Paul Lemoine 1967 characterized alcohol as
teratogen
bull Kenneth Lyon Jones 1973 (dysmorphologist)
coined term fetal alcohol syndrome (typically
14 or more drinks daily)
What we know Risk of alcohol
bull Not controversial excessive alcohol use (gt2 units per
day or gt4 units per sitting) DOSE RESPONSE
ndash Increased risk of miscarriage reduction in fetal growth
impaired neurodevelopment (American Academy of
Pediatrics 2000) low birth weight (Patra 2011)
ndash Preterm birth (Albertsen et al 2004)
ndash Dose response effect on FAS (Rehm 2010)
ndash Withdrawal in infant
What we know Risk of alcohol
bull Controversial
ndash Mixed evidence that low-levels of drinking pose risk
to fetus or mother (NICE March 2008) but no
consensus on what ldquolow levelrdquo is
ndash Several countries have wrestled with how to advise
pregnant women on alcohol use Australia Denmark
American Academy of Pediatrics November 2015
bull During pregnancy
ndash no amount of alcohol intake should be considered safe
ndash there is no safe trimester to drink alcohol
ndash all forms of alcohol such as beer wine and liquor pose
similar risk and
ndash binge drinking poses dose-related risk to the developing
fetus
(Williams et al 2015)
MAT for AUD in Pregnancy
bull Disulfiram (Antabuse)
bull Naltrexone (Revia Vivitrol)
bull Acamprosate (Campral)
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
bull Gender Differences in Substance Use Disorders decreasing (Keyes 2008)
bull Telescoping (Randall 1999)
bull When present for treatment report greater impairment relative to men in employment social psychiatric and medical domains (Hernandez-Avila et al 2004)
bull More likely to use substances than men to manage negative affects (Saladin et al 2012)
bull Less than 20 of those women who need treatment receive it yearly (Terplan et al 2012)
bull Women less likely to engage in treatment than men (Back et al 2010) bull Among pregnant women perception of risk is important predictor of use (Blume
et al 2007)
Epidemiology of Addiction in Reproductive Age Women
Prevalence of Illicit Substance Cigarette and Alcohol Use in Pregnant Women
Laura P McLafferty Madeleine Becker Nehama Dresner Samantha Meltzer-Brody Priya Gopalan Jody Glance Guitelle St
Victor Leena Mittal Patrick Marshalek Laura Lander Linda LM Worley
Guidelines for the Management of Pregnant Women With Substance Use Disorders
Psychosomatics Volume 57 Issue 2 2016 115ndash130
httpdxdoiorg101016jpsym201512001
Epidemiology of Addiction in Pregnant Women
Epidemiology of Addiction in Pregnant Women
bull Women generally decrease use during pregnancy bull Danish study 90 of women reduced intake of
EtOH upon learning of pregnancy (Kesmodel et al 2003)
bull NSDUH 2010
Pregnant () Not Pregnant ()
Current EtOH Use 108 547
Binge Drinking 37 246
Heavy Drinking 1 54
Alcohol Use Disorders and Pregnancy
Hogarthrsquos Gin Lane (1751)
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
hellipmore historical notes
bull Paul Lemoine 1967 characterized alcohol as
teratogen
bull Kenneth Lyon Jones 1973 (dysmorphologist)
coined term fetal alcohol syndrome (typically
14 or more drinks daily)
What we know Risk of alcohol
bull Not controversial excessive alcohol use (gt2 units per
day or gt4 units per sitting) DOSE RESPONSE
ndash Increased risk of miscarriage reduction in fetal growth
impaired neurodevelopment (American Academy of
Pediatrics 2000) low birth weight (Patra 2011)
ndash Preterm birth (Albertsen et al 2004)
ndash Dose response effect on FAS (Rehm 2010)
ndash Withdrawal in infant
What we know Risk of alcohol
bull Controversial
ndash Mixed evidence that low-levels of drinking pose risk
to fetus or mother (NICE March 2008) but no
consensus on what ldquolow levelrdquo is
ndash Several countries have wrestled with how to advise
pregnant women on alcohol use Australia Denmark
American Academy of Pediatrics November 2015
bull During pregnancy
ndash no amount of alcohol intake should be considered safe
ndash there is no safe trimester to drink alcohol
ndash all forms of alcohol such as beer wine and liquor pose
similar risk and
ndash binge drinking poses dose-related risk to the developing
fetus
(Williams et al 2015)
MAT for AUD in Pregnancy
bull Disulfiram (Antabuse)
bull Naltrexone (Revia Vivitrol)
bull Acamprosate (Campral)
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Prevalence of Illicit Substance Cigarette and Alcohol Use in Pregnant Women
Laura P McLafferty Madeleine Becker Nehama Dresner Samantha Meltzer-Brody Priya Gopalan Jody Glance Guitelle St
Victor Leena Mittal Patrick Marshalek Laura Lander Linda LM Worley
Guidelines for the Management of Pregnant Women With Substance Use Disorders
Psychosomatics Volume 57 Issue 2 2016 115ndash130
httpdxdoiorg101016jpsym201512001
Epidemiology of Addiction in Pregnant Women
Epidemiology of Addiction in Pregnant Women
bull Women generally decrease use during pregnancy bull Danish study 90 of women reduced intake of
EtOH upon learning of pregnancy (Kesmodel et al 2003)
bull NSDUH 2010
Pregnant () Not Pregnant ()
Current EtOH Use 108 547
Binge Drinking 37 246
Heavy Drinking 1 54
Alcohol Use Disorders and Pregnancy
Hogarthrsquos Gin Lane (1751)
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
hellipmore historical notes
bull Paul Lemoine 1967 characterized alcohol as
teratogen
bull Kenneth Lyon Jones 1973 (dysmorphologist)
coined term fetal alcohol syndrome (typically
14 or more drinks daily)
What we know Risk of alcohol
bull Not controversial excessive alcohol use (gt2 units per
day or gt4 units per sitting) DOSE RESPONSE
ndash Increased risk of miscarriage reduction in fetal growth
impaired neurodevelopment (American Academy of
Pediatrics 2000) low birth weight (Patra 2011)
ndash Preterm birth (Albertsen et al 2004)
ndash Dose response effect on FAS (Rehm 2010)
ndash Withdrawal in infant
What we know Risk of alcohol
bull Controversial
ndash Mixed evidence that low-levels of drinking pose risk
to fetus or mother (NICE March 2008) but no
consensus on what ldquolow levelrdquo is
ndash Several countries have wrestled with how to advise
pregnant women on alcohol use Australia Denmark
American Academy of Pediatrics November 2015
bull During pregnancy
ndash no amount of alcohol intake should be considered safe
ndash there is no safe trimester to drink alcohol
ndash all forms of alcohol such as beer wine and liquor pose
similar risk and
ndash binge drinking poses dose-related risk to the developing
fetus
(Williams et al 2015)
MAT for AUD in Pregnancy
bull Disulfiram (Antabuse)
bull Naltrexone (Revia Vivitrol)
bull Acamprosate (Campral)
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Epidemiology of Addiction in Pregnant Women
bull Women generally decrease use during pregnancy bull Danish study 90 of women reduced intake of
EtOH upon learning of pregnancy (Kesmodel et al 2003)
bull NSDUH 2010
Pregnant () Not Pregnant ()
Current EtOH Use 108 547
Binge Drinking 37 246
Heavy Drinking 1 54
Alcohol Use Disorders and Pregnancy
Hogarthrsquos Gin Lane (1751)
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
hellipmore historical notes
bull Paul Lemoine 1967 characterized alcohol as
teratogen
bull Kenneth Lyon Jones 1973 (dysmorphologist)
coined term fetal alcohol syndrome (typically
14 or more drinks daily)
What we know Risk of alcohol
bull Not controversial excessive alcohol use (gt2 units per
day or gt4 units per sitting) DOSE RESPONSE
ndash Increased risk of miscarriage reduction in fetal growth
impaired neurodevelopment (American Academy of
Pediatrics 2000) low birth weight (Patra 2011)
ndash Preterm birth (Albertsen et al 2004)
ndash Dose response effect on FAS (Rehm 2010)
ndash Withdrawal in infant
What we know Risk of alcohol
bull Controversial
ndash Mixed evidence that low-levels of drinking pose risk
to fetus or mother (NICE March 2008) but no
consensus on what ldquolow levelrdquo is
ndash Several countries have wrestled with how to advise
pregnant women on alcohol use Australia Denmark
American Academy of Pediatrics November 2015
bull During pregnancy
ndash no amount of alcohol intake should be considered safe
ndash there is no safe trimester to drink alcohol
ndash all forms of alcohol such as beer wine and liquor pose
similar risk and
ndash binge drinking poses dose-related risk to the developing
fetus
(Williams et al 2015)
MAT for AUD in Pregnancy
bull Disulfiram (Antabuse)
bull Naltrexone (Revia Vivitrol)
bull Acamprosate (Campral)
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Alcohol Use Disorders and Pregnancy
Hogarthrsquos Gin Lane (1751)
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
hellipmore historical notes
bull Paul Lemoine 1967 characterized alcohol as
teratogen
bull Kenneth Lyon Jones 1973 (dysmorphologist)
coined term fetal alcohol syndrome (typically
14 or more drinks daily)
What we know Risk of alcohol
bull Not controversial excessive alcohol use (gt2 units per
day or gt4 units per sitting) DOSE RESPONSE
ndash Increased risk of miscarriage reduction in fetal growth
impaired neurodevelopment (American Academy of
Pediatrics 2000) low birth weight (Patra 2011)
ndash Preterm birth (Albertsen et al 2004)
ndash Dose response effect on FAS (Rehm 2010)
ndash Withdrawal in infant
What we know Risk of alcohol
bull Controversial
ndash Mixed evidence that low-levels of drinking pose risk
to fetus or mother (NICE March 2008) but no
consensus on what ldquolow levelrdquo is
ndash Several countries have wrestled with how to advise
pregnant women on alcohol use Australia Denmark
American Academy of Pediatrics November 2015
bull During pregnancy
ndash no amount of alcohol intake should be considered safe
ndash there is no safe trimester to drink alcohol
ndash all forms of alcohol such as beer wine and liquor pose
similar risk and
ndash binge drinking poses dose-related risk to the developing
fetus
(Williams et al 2015)
MAT for AUD in Pregnancy
bull Disulfiram (Antabuse)
bull Naltrexone (Revia Vivitrol)
bull Acamprosate (Campral)
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Hogarthrsquos Gin Lane (1751)
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
hellipmore historical notes
bull Paul Lemoine 1967 characterized alcohol as
teratogen
bull Kenneth Lyon Jones 1973 (dysmorphologist)
coined term fetal alcohol syndrome (typically
14 or more drinks daily)
What we know Risk of alcohol
bull Not controversial excessive alcohol use (gt2 units per
day or gt4 units per sitting) DOSE RESPONSE
ndash Increased risk of miscarriage reduction in fetal growth
impaired neurodevelopment (American Academy of
Pediatrics 2000) low birth weight (Patra 2011)
ndash Preterm birth (Albertsen et al 2004)
ndash Dose response effect on FAS (Rehm 2010)
ndash Withdrawal in infant
What we know Risk of alcohol
bull Controversial
ndash Mixed evidence that low-levels of drinking pose risk
to fetus or mother (NICE March 2008) but no
consensus on what ldquolow levelrdquo is
ndash Several countries have wrestled with how to advise
pregnant women on alcohol use Australia Denmark
American Academy of Pediatrics November 2015
bull During pregnancy
ndash no amount of alcohol intake should be considered safe
ndash there is no safe trimester to drink alcohol
ndash all forms of alcohol such as beer wine and liquor pose
similar risk and
ndash binge drinking poses dose-related risk to the developing
fetus
(Williams et al 2015)
MAT for AUD in Pregnancy
bull Disulfiram (Antabuse)
bull Naltrexone (Revia Vivitrol)
bull Acamprosate (Campral)
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
httpwwwtelegraphcoukhealthhealthadvicemaxpemberton9769425William-Hogarths-Gin-Lane-has-a-lesson-for-binge-drinking-Britainhtml
hellipmore historical notes
bull Paul Lemoine 1967 characterized alcohol as
teratogen
bull Kenneth Lyon Jones 1973 (dysmorphologist)
coined term fetal alcohol syndrome (typically
14 or more drinks daily)
What we know Risk of alcohol
bull Not controversial excessive alcohol use (gt2 units per
day or gt4 units per sitting) DOSE RESPONSE
ndash Increased risk of miscarriage reduction in fetal growth
impaired neurodevelopment (American Academy of
Pediatrics 2000) low birth weight (Patra 2011)
ndash Preterm birth (Albertsen et al 2004)
ndash Dose response effect on FAS (Rehm 2010)
ndash Withdrawal in infant
What we know Risk of alcohol
bull Controversial
ndash Mixed evidence that low-levels of drinking pose risk
to fetus or mother (NICE March 2008) but no
consensus on what ldquolow levelrdquo is
ndash Several countries have wrestled with how to advise
pregnant women on alcohol use Australia Denmark
American Academy of Pediatrics November 2015
bull During pregnancy
ndash no amount of alcohol intake should be considered safe
ndash there is no safe trimester to drink alcohol
ndash all forms of alcohol such as beer wine and liquor pose
similar risk and
ndash binge drinking poses dose-related risk to the developing
fetus
(Williams et al 2015)
MAT for AUD in Pregnancy
bull Disulfiram (Antabuse)
bull Naltrexone (Revia Vivitrol)
bull Acamprosate (Campral)
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
hellipmore historical notes
bull Paul Lemoine 1967 characterized alcohol as
teratogen
bull Kenneth Lyon Jones 1973 (dysmorphologist)
coined term fetal alcohol syndrome (typically
14 or more drinks daily)
What we know Risk of alcohol
bull Not controversial excessive alcohol use (gt2 units per
day or gt4 units per sitting) DOSE RESPONSE
ndash Increased risk of miscarriage reduction in fetal growth
impaired neurodevelopment (American Academy of
Pediatrics 2000) low birth weight (Patra 2011)
ndash Preterm birth (Albertsen et al 2004)
ndash Dose response effect on FAS (Rehm 2010)
ndash Withdrawal in infant
What we know Risk of alcohol
bull Controversial
ndash Mixed evidence that low-levels of drinking pose risk
to fetus or mother (NICE March 2008) but no
consensus on what ldquolow levelrdquo is
ndash Several countries have wrestled with how to advise
pregnant women on alcohol use Australia Denmark
American Academy of Pediatrics November 2015
bull During pregnancy
ndash no amount of alcohol intake should be considered safe
ndash there is no safe trimester to drink alcohol
ndash all forms of alcohol such as beer wine and liquor pose
similar risk and
ndash binge drinking poses dose-related risk to the developing
fetus
(Williams et al 2015)
MAT for AUD in Pregnancy
bull Disulfiram (Antabuse)
bull Naltrexone (Revia Vivitrol)
bull Acamprosate (Campral)
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
What we know Risk of alcohol
bull Not controversial excessive alcohol use (gt2 units per
day or gt4 units per sitting) DOSE RESPONSE
ndash Increased risk of miscarriage reduction in fetal growth
impaired neurodevelopment (American Academy of
Pediatrics 2000) low birth weight (Patra 2011)
ndash Preterm birth (Albertsen et al 2004)
ndash Dose response effect on FAS (Rehm 2010)
ndash Withdrawal in infant
What we know Risk of alcohol
bull Controversial
ndash Mixed evidence that low-levels of drinking pose risk
to fetus or mother (NICE March 2008) but no
consensus on what ldquolow levelrdquo is
ndash Several countries have wrestled with how to advise
pregnant women on alcohol use Australia Denmark
American Academy of Pediatrics November 2015
bull During pregnancy
ndash no amount of alcohol intake should be considered safe
ndash there is no safe trimester to drink alcohol
ndash all forms of alcohol such as beer wine and liquor pose
similar risk and
ndash binge drinking poses dose-related risk to the developing
fetus
(Williams et al 2015)
MAT for AUD in Pregnancy
bull Disulfiram (Antabuse)
bull Naltrexone (Revia Vivitrol)
bull Acamprosate (Campral)
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
What we know Risk of alcohol
bull Controversial
ndash Mixed evidence that low-levels of drinking pose risk
to fetus or mother (NICE March 2008) but no
consensus on what ldquolow levelrdquo is
ndash Several countries have wrestled with how to advise
pregnant women on alcohol use Australia Denmark
American Academy of Pediatrics November 2015
bull During pregnancy
ndash no amount of alcohol intake should be considered safe
ndash there is no safe trimester to drink alcohol
ndash all forms of alcohol such as beer wine and liquor pose
similar risk and
ndash binge drinking poses dose-related risk to the developing
fetus
(Williams et al 2015)
MAT for AUD in Pregnancy
bull Disulfiram (Antabuse)
bull Naltrexone (Revia Vivitrol)
bull Acamprosate (Campral)
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
American Academy of Pediatrics November 2015
bull During pregnancy
ndash no amount of alcohol intake should be considered safe
ndash there is no safe trimester to drink alcohol
ndash all forms of alcohol such as beer wine and liquor pose
similar risk and
ndash binge drinking poses dose-related risk to the developing
fetus
(Williams et al 2015)
MAT for AUD in Pregnancy
bull Disulfiram (Antabuse)
bull Naltrexone (Revia Vivitrol)
bull Acamprosate (Campral)
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
MAT for AUD in Pregnancy
bull Disulfiram (Antabuse)
bull Naltrexone (Revia Vivitrol)
bull Acamprosate (Campral)
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
What about alcohol withdrawal
bull Extrapolate from physiology but no consensus on risk
of withdrawal specifically
ndash Risks to mother
ndash Intrauterine Seizures (Seizure risk elevated in FASFASD
children)
ndash Hypertensionautonomic instability risks
ndash Cortisol
ndash Delirium Tremenscould harm selffetus
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
What we know Risk of BZs
bull Two camps
1 Benzos cause malformations
bull Dolovich 1998 meta-analysis of cohort and case control
studies CCS showed OR of MM 301 and oral cleft 179
bull Iqbal 2002 systemmatic review looked at individual meds not
just class Klonopin and xanax some risk but no pattern Ativan
linked to anal atresia
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
What we know Risk of BZs bull Problems with this data
ndash Did NOT consistently define
raquo the gestational age at exposure
raquo concurrent substances used
raquo dose of exposure
raquo clear psychiatric indication provided
raquo Data were not collected on MM in fetuses spontaneously
aborted after BZD overdose (up to 28)
ndash Since compelling data for association came from case-control
studies bringing into question recall biases
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
What we know Risk of BZs
2 Benzos donrsquot cause malformations
bull Reis 2013 Swedish National Health Registries
(survey) 3000+ infants born to mothers exposed to
BZs aloneno increased risk of MM
bull Bellantuono 2013 Critical reviewfirst trimester
exposure amp MM Ativan risk of anal atresia 310000
to 2010000
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
What we know Risk of BZs
ndash Late third trimester risk of floppy infant
syndrome (McElhatton 1994)
bull Mild sedation
bull Hypotonia
bull Apneic spells
bull cyanosis
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Changing Gearshellip
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders and Pregnancy
Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges
First Published July 14 2014
Available on httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
OUDmdashMaternal Risks bull Infectious Diseases
ndash HIV
ndash Hepatitis B and C
ndash Other infections related to use cellulitis endocarditis
bull Overdose
bull Pain management before during and after delivery
bull Psychosocial challenges often co-occurring with opioid use disorders
prostitution theft violence to support habit(s) domestic violence
incarceration and other legal problems poor engagement in prenatal
care
bull Psychiatric comorbidities depression and anxiety along with opioid use
disorders lead to worse treatment outcomes (Benningfield 2012)
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
OUDmdashFetal Risks
bull Low birth weight (Hulse 1997)
bull Birth defects (congenital heart defects associated with first
trimester codeine exposure) (Zierler 1985 Bracken 1986)
bull Fetal growth restriction
bull Abruptio placentae fetal death preterm labor and intrauterine
passage of meconium
bull Postulated to be related to withdrawalintoxication cycles of
mother
bull (Center for Substance Abuse Treatment Medication-assisted treatment for opioid addiction
during pregnancy 2008)
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy IMPORTANT NOTE
bull Heroin (untreated) a 6-fold increase in risk of obstetrical
complications and a 74-fold increase in risk of sudden infant death
syndrome (Dattel 1990 Fajemirokun 2006 Ludlow 2004)
bull While both buprenorphine and methadone carry risks these risks
are felt to be minor relative to ongoing untreated heroin or other
non-medical opioid use
ndash Both methadone and buprenorphine allow for more steady blood
levels of opioids (Jarvis 1994 Rayburn 2004 respectively) that
prevents exposure to repeated fetalmaternal withdrawal events
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Screening ToolsmdashCRAFFT
bull CRAFFT (Chang 2011)mdashvalidated in pregnant women in addition to adolescents
ndash Have you ever ridden in a car with someone (including yourself) who
was ldquohighrdquo or had been using alcohol or drugs
ndash Do you ever use alcohol or drugs to relax feel better about yourself
or fit in
ndash Do you ever use alcohol or drugs while you are by yourself alone
ndash Do you ever forget things you did while using alcohol or drugs
ndash Do your family or friends ever tell you that you should cut down on
your drinking or drug use
ndash Have you ever gotten into trouble while you were using alcohol or
drugs
ndash Advantage Open-source
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Screening ToolsmdashOther
bull TWEAK
ndash Tolerance Worried Eye-Opener Amnesia KCut Down
ndash Validated screen for peri-conceptual risky drinking (Russell 1994)
bull T-ACE
ndash Tolerance Annoyance Cut Down Eye-Opener
ndash Validated screen for peri-conceptual risky drinking (Russell 1994
Sokol 1989)
ndash Vs CRAFFT (Chang 2011)mdashCRAFFT better at detecting past 6 month
usage of drugs or alcohol T-ACE better at picking up lifetime alcohol
use
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Detoxification in pregnancy bull Zuspan 1975 fetal distress during methadone detox
bull Rementeria 1973 5-fold increase in stillbirth incidence
following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd ndash Luty 2003 retrospective case series of 101 pregnant women who
underwent 21 day inpatient methadone withdrawal15 miscarriage in 1st trimester 054 in 2nd no difference relative to general population in 3rd
bull Maintenance therapy in pregnancy has been shown to increase retention in prenatal care addiction recovery and in-hospital deliveries (Jones et al 2008)
bull As with outcome measures in non-pregnant individuals use of MAT (buprenorphine or methadone) as part of a comprehensive care approach to pregnant woman improves maternal and neonatal outcomes (Jones 2011 Winklbauer 2008 Kaltenbach 1998)
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Detoxification in pregnancy
bull Fetal distress during detox
bull Increase in stillbirth incidence following opioid withdrawal
bull Second trimester detoxification may be safer than 1st or 3rd
bull Maintenance therapy increase retention in prenatal care addiction recovery and in-hospital deliveries improved neonatal and maternal outcomes
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Medication Assisted Treatment (MAT)
bull There are three general categories of MAT
ndash Mu opioid antagonism with naltrexone
ndash Mu opioid agonismpartial agonism with either
bull Methadone
bull Buprenorphine
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Naltrexone
bull Pure opioid antagonist at mu kappa and delta opioid receptors (highest affinity for mu)
bull Available in oral and long-acting injectable forms
bull Food and Drug Administration (FDA) safety category in pregnancy C
ndash Meaning either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal effects or other) and there are no controlled studies in women or studies in women and animals are not available Drugs should be given only if the potential benefits justify the potential risk to the fetus
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid (mu
kappa delta) receptors is not well known Animal studies have shown
developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Naltrexone
bull Not currently approved or recommended in pregnancy
bull Benefits
ndash no risk of NAS
ndash NOT a controlled substance (does not require special licensure)
bull Risks
ndash Long-term effects on fetal development due to blockade of opioid
(mu kappa delta) receptors is not well known Animal studies have
shown developmental and behavioral changes in adult rats exposed to
naltrexone in utero but humans studies on developmental and
behavioral sequelae are lacking (Farid 2012 White 2013)
ndash Requires detoxification from opioids
ndash High rates of relapsedropout from treatment (Waal 2013)
ndash Possible complications for pain management during and post-delivery
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Management of Patient Newly Pregnant
bull For women already stable on buprenorphinenaloxone who become pregnant ndash Current standard of care is to switch to
buprenorphine monotherapy at the same dose
bull For women already stable on methadone ndash Current standard of care is to remain on
methadone bull Patient may need dose increase or split
dosing
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Methadone
httpwwwmethadoneaddictioncomwp-contentuploads201412methadonejpg
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Methadone
bull Synthetic Mu opioid receptor agonist and N-
methyl-D-aspartate (NMDA) receptor antagonist
bull FDA safety category in pregnancy C
ndash Considered standard of care for MAT in pregnant
women in US although NOT FDA approved for this
indication
bull Crosses placenta
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Methadone
bull Requires engagement in federally sanctioned methadone
treatment programsclinics (42 Code of Federal Regulations (CFR)
Section 812)
bull Benefits
ndash Pregnant women in MTPs have improved fetal outcomes
compared to pregnant women using illicit drugs (ACOG 2012)
ndash Structured clinic setting with additional substance use
disorder treatment programming
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Risks of Methadone Use in Pregnancy
bull Risks
ndash Fetal growth birth weight length andor head circumference may be
decreased but these effects do not appear to persist (ACOG 2012)
ndash Decreased psychometric and behavioral tests has been found to persist into
childhood (ACOG 2012)
ndash NAS up to 2-4 weeks after delivery
ndash Increased clearance and decreased half-life in pregnant women (2nd and 3rd
trimesters) requiring increased dosing amounts and frequencies and
decrease after delivery (ACOG 2012)
ndash Many drug-drug interactions
ndash QTc prolongation constipation diaphoresis
ndash May complicate pain management acutely owing to blockade of mu
receptors
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Buprenorphine
httpsuploadwikimediaorgwikipediacommonsthumbbb0Buprenorphinesvg2000px-Buprenorphinesvgpng
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Buprenorphine
bull High-affinity Mu opioid receptor partial agonist and kappa
opioid receptor antagonist
bull FDA safety category in pregnancy C
bull Crosses placenta
bull Available in diversion-deterrent formulation combined
with naloxone
bull Recommendation in pregnancy is to use buprenorphine
alone due to potential risks posed by naloxone
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Buprenorphine
bull Benefits
ndash Office based does not require clinic although some buprenorphine clinics available for daily
dosing
ndash Ceiling effect for respiratory suppression (although this is eliminated when using
benzodiazepines concurrently)
ndash Maintain in treatment
bull Risks
ndash NAS
ndash Constipation diaphoresis
ndash Possible complications for acute pain management due to high affinity blockade of mu
opioid receptors
ndash Lower head circumference and birth weights (Hytinantii 2008)
ndash Need for safeguarding medication
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull Multi-site randomized controlled trial (Jones et al 2010)
bull Buprenorphine ndash Fewer dose adjustments
ndash Fewer drug-drug interactions
ndash Ceiling effect
ndash Office-based
ndash Less NAS shorter hospital stays (Jones et al NEJM 2010)
ndash More drop-out relative to methadone (33 vs 18 respectively) (Jones et al NEJM 2010)
bull Methadone ndash More available data on long-term developmental and behavioral outcomes
ndash Structure provided by clinic setting
ndash Potentially easier acute pain management relative to buprenorphine
ndash More familiarity amongst hospital staff and other providers
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
0
10
20
30
40
50
60
70
80
90
100
Mu Receptor
Intrinsic Activity
Full Agonist (methadone)
Partial Agonist (buprenorphine)
Full Antagonist (eg naloxone)
no drug high dose
DRUG DOSE
low dose
Slide from The ASAM Buprenorphine CoursemdashStock set
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Buprenorphine vs Methadone
bull ldquoThe current trend is moving toward considering a patient as a potential
candidate for buprenorphine if she prefers buprenorphine to methadone
gives informed consent after a thorough discussion of relative risks and
benefits and is capable of adherence and safe self-administration of the
medication If the pregnant woman is receiving methadone therapy she
should not consider transitioning to buprenorphine because of the
significant risk of precipitated withdrawal The potential risk of
unrecognized adverse long-term outcomes which is inherent with
widespread use of relatively new medications during pregnancy should
always be taken into considerationrdquo (ACOG 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Maintenance Therapy in Pregnancy Neonatal Abstinence Syndrome (NAS)
Meta-analysis of 12 studies from 1996-2012 showed
buprenorphine exposed neonates (515) compared to
methadone exposed (855) had
Shorter mean length of hospital stay (-723 days 95 CI -1064 -383)
In treated neonates buprenorphine exposed
Shorter NAS treatment duration(-846 days 95 CI -1448 -244)
Lower morphine dose (-360 mg 95 CI -726 007)
Brogly et al 2014
Slide from The ASAM Buprenorphine CoursemdashStock set
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Maternal Dose and NAS Severity
bull No correlation between maternal opioid
maintenance therapy dose and the duration or
severity of NAS (Berghella 2003)
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Breastfeeding is beneficial to infant and mother
ndash Mother-infant bonding (Tharner 2012)
ndash Infant benefits Decreased incidence of otitis media
gastroenteritis severe lower respiratory tract infections
childhood leukemia type 1 amp 2 diabetes obesity asthma
sudden infant death syndrome and necrotizing enterocolitis (Ip
2007)
ndash Mother benefits Decreased incidence of type 2 diabetes
breastovarian cancer and post partum depression (Ip 2007)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding
bull Naltrexone
ndash Enters breast milk (manufacturer does not
recommend breastfeeding while on this medication)
ndash Little data on its safety for use in breastfeeding
(animal data demonstrates some potential
tumorigenicitymdashproduct information Vivitrol 2010)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Buprenorphine
ndash Excreted in breast milk
bull Manufacturer does not recommend breastfeeding while on this
medication
bull However most guidelines do not contraindicate usage while
breastfeeding (ACOG 2012 CSAT 2004 Montgomery 2012)
bull Little is bioavailable to infant owing in part to the need for sublingual
absorption [Samples from single mother-infant pair demonstrated
daily infant ingestion of 328mcg from a lactating mother receiving
4mg daily (Marquet 1997)]
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT vv
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull 18 states consider maternal substance use ldquochild abuserdquo (1 state considers
it ldquocriminalrdquo)
bull 3 states consider it grounds for civil commitments (MN SD WI)
bull 18 states require health care providers to report suspected prenatal
substance abuse
bull 4 states require them to test if they suspect it
bull 19 states have targeted programs for pregnant women
bull 13 states provide pregnant women with priority access to state substance
abuse programs
bull For more information refer to
bull httpwwwguttmacherorgstatecenterspibsspib_SADPpdf
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy MAT and LactationBreastfeeding bull Methadone
ndash Excreted in breast milk
bull Dose to a nursing infant is 2-3 of maternal dose (10-80mg maternal methadone daily
dosing)
ndash Manufacturer does not recommend breastfeeding while on this medication
ndash However most guidelines do not contraindicate usage while breastfeeding
(ACOG 2012)
ndash If illicit drugs are being used while mother is taking methadone it is
recommended that breast milk is pumped and discarded until sobriety is
achieved (ACOG 2012 Dow 2012)
DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges PCSS-MAT
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Opioid Use Disorders amp Pregnancy Mandatory reporting
considerations bull California
ndash Positive urine toxicology screen in infant born to
mother either in or not in MAT does not mandate
reporting It is at the discretion of the provider to
assess the need for reporting to county welfare
department police or probation department
ndash See httpmandatedreportercacomimagesPub132pdf
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Altered Pain Experience
bull Patients with opioid use disorder (actively using) have lower pain
tolerance than those in remission or matched controls
bull Patients on opioid maintenance treatment (ie methadone
buprenorphine) have less pain tolerance then matched controls
bull ldquoOpioid Debtrdquo
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Buprenorphine is good analgesic (without analgesic
ceiling)
Can combine buprenorphine with short acting opioids and
will have synergistic effect
Acute Pain Buprenorphine Maintenance Treatment
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Changing Gearshellip
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Amphetamines
bull Prescribed bull Almost completely unstudied
bull Illicit
httpsiytimgcomviVqPXSdkeumEhqdefaultjpg
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Amphetamines
bull Illicit bull Comorbidities
bull 78 active tobacco smokers bull 14 regular alcohol users bull 24 regularly tested positive for multiple
substances (Uziel-Miller 2002)
bull Risks bull No evidence that they are teratogenic bull Small-for-gestational age (Plessinger 1998) bull Neonatal and childhood behavioral abnormalities
(Plessinger 1998 ACOG 2011)
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Amphetamines bull Illicit
bull Risks cont bull Intrauterine growth restriction (anorexia) (Smith et al 2006) bull decreased arousal increased stress and poor movement in newborns
(Della Grotta S et al 2010) bull Maternalfetal hypertension (poorly studied) (ACOG 2011) bull Infants trouble feeding sleep disruption and abnormalities of muscle
tone bull resolve spontaneously within several weeks
bull Inhibits prolactin bull Serummilk of 11 to 175 bull Stopping cold turkeydepression paranoia fatigue anergia bull Placental abruption (due to vasocontriction) actually see LARGER
placenta (thought to be related to chronic hypoxia like at altitude) (Carter et al 2016)
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Amphetamines bull Illicit
bull Treatment bull No MAT bull CBT Contingency Management (Rawson et al
2004 Roll et al 2006)
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Conclusions bull While the numbers of women with SUD in pregnancy are lower
than in the general population they still present significant risks
bull Alcohol is known teratogen but dose exposure uncertain bull Decisions regarding MAT in pregnancy need to be carefully
weighed in risk-benefit discussion bull Alcohol withdrawal could pose particular risk to mother and infant
bull Data suggest treatment of withdrawal with benzodiazepines
unlikely to have deleterious effects
bull No amount of alcohol is considered ldquosaferdquo during pregnancy
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Conclusions bull Opioid detoxification during pregnancy is risky
and maintenance treatment with either buprenorphine or methadone is preferred
bull Buprenorphine and methadone each present unique pros and cons
bull Despite some cons MAT is preferred over continued use
bull Generally speaking women are encouraged to breastfeed while on MAT
bull Check with your state regarding mandatory reporting laws
bull We have no medication treatments for amphetamine use disorders and amphetamine use carries unique maternalfetal risks
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
Resources
bull AAAP bull wwwaaaporg
bull ASAMCSAM bull wwwasamorg bull wwwcsam-asamorg
bull PCSS-O bull wwwpcss-oorg
bull PCSS-MAT bull wwwpcssmatorg
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
References bull Albertsen K Andersen A M Olsen J amp Groslashnbaek M (2004) Alcohol consumption during pregnancy and the risk of preterm delivery American Journal of Epidemiology 159 155-161
bull American Academy of Pediatrics Committee on substance abuse and committee on children with disabilities Fetal alcohol syndrome and alcohol related neruodevelopmental disorders Pediatrics 2000106358ndash
61
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 524 May 2012 (reaffirmed 2014) Available on httpwwwacogorgResources-And-PublicationsCommittee-OpinionsCommittee-on-Health-Care-for-Underserved-WomenOpioid-
Abuse-Dependence-and-Addiction-in-Pregnancy
bull American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women and the American Society of Addiction Medicine Opioid Abuse Dependence and Addiction in
Pregnancy Number 479 May 2011 Obstet Gynecol 117 (2011) 751-755
bull Back SE Payne RL Simpson AN et al Gender and prescription opioids findings from the National Survey on Drug Use and Health Addict Behav 2010351001-7
bull Bellantuono et al Benzodiazepine exposure in pregnancy and risk of major malformations a critical review General Hospital Psychiatry Vol 35 Issue 1 Jan-Feb 2013 pg 3-8
bull Benningfield MM Dietrich MS Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OGrady KE Fischer G Martin PR Opioid dependence during pregnancy relationships of anxiety and depression
symptoms to treatment outcomes Addiction 2012107 Suppl 174-82
bull Berghella V Lim PJ Hill MK Cherpes J Chennat J Kaltenbach K Maternal methadone dose and neonatal withdrawal Am J Obstet Gynecol 2003 Aug 189(2)312-7
bull Blume AW Resor MR Knowledge about health risks and drinking behavior among Hispanic women who are or have been of childbearing age Addict Behav 2007322335-9
bull Bracken MB Drug use in pregnancy and congenital heart disease in offspring N Engl J Med 1986 3141120
bull Brogly SB Saia KA Walley AY Du HM Sebatiani P Prenatal Buprenorphine versus methadone exposure and neonatal outcomes systematic review and meta-analysis Am J Epidemiol 2014 Oct 1 180(7) 673-
86
bull Carter RC Wainwright H Molteno CD Georgieff MK Dodge NC Warton F Meinjes EM Jacobson JL Jacobson SW Alcohol Methamphetamine and Marijuana Exposure have distinct effects on the human
placenta Alcohol Clin Exp Res 40(4) 2016 753-764
bull Center for Substance Abuse Treatment (CSAT) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction Treatment Improvement Protocol (TIP) Series 40 DHHS Publication No (SMA)
04‐3939 Rockville MD Substance Abuse and Mental Health Services Administration 2004
bull Center for Substance Abuse Treatment Medication- assisted treatment for opioid addiction during pregnancy In SAHMSACSAT treatment improvement protocols Rockville (MD) Substance Abuse and
Mental Health Services Administration 2008 Available at httpwwwncbi nlmnihgovbooksNBK26113
bull Chang G Orav EJ Jones JA Buynitsky T Gonzalez S Wilkins-Haug L Self-reported alcohol and drug use in pregnant young women a pilot study of associated factors and identification J Addict Med 20115221ndash
6
bull Dattel B Substance abuse in pregnancy Seminars in Perinatology 199014(2)179ndash87
bull Della Grotta S LaGasse LL Arria AM et al Patterns of methamphetamine use during pregnancy results from the Infant Development Environment and Lifestyle (IDEAL) Study Matern Child Health J
14(2010)519-527
bull DeVido J Greenfield S Opioid Dependence in Pregnancy Clinical Challenges Providerrsquos Clinical Support SystemmdashMedication Assisted Treatment (PCSS-MAT) First Published July 14 2014 Available on
httppcssmatorgopioid-dependence-in-pregnancy-clinical-challenges
bull Dolovich et al (Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and casendashcontrol studies BMJ 317 (1998) pp 839ndash843
bull Dow K Ordean A Murphy-Oikonen J et al Neonatal Abstinence Syndrome Clinical Practice Guidelines For Ontario J Popul Ther Clin Pharmacol 2012 19(3)e488-506
bull Ewing H A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics theoretical framework brief screening tool key interview questions and strategies
for referral to recovery resources Martinez (CA) The Born Free Project Contra Costa County Department of Health Services 1990
References bull Farid WO Lawrence AJ Krstew EV Tait RJ Hulse GK et al (2012) Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood PLoS ONE 7(12)
e52812 doi101371journalpone0052812
bull Fajemirokun-Odudeyi O Sinha C Tutty S Pairaudeau P Armstrong D Phillips T et alPregnancy outcome in women who use opiates European Journal of Obstetrics Gynecology and Reproductive Biology
2006126(2)170ndash5
bull Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid- cannabis- and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 200474265-72
bull Hulse GK Milne E English DR et al The relationship between maternal use of heroin and methadone and infant birth weight Addiction 1997921571-9
bull Hytinantti T Kahila H Renlund M et al Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero Acta Paediatr 2008 97(8)1040-1044
bull Ip S Chung M Raman G Chew P Magula N DeVine D et al Breastfeeding and maternal and infant health outcomes in developed countries Evid Rep Technol Assess (Full Rep) 2007 153 1ndash186
bull Iqbal 2002 systemmatic review Effects of commonly used benzodiazepines on the fetus the neonate and the nursing infant Psychiatr Serv 53 (2002) pp 39ndash49
bull Jones HE Kaltenbach K Heil SH Stine SM Coyle MG Arria AM OrsquoGrady KE Selby P Martin PR Fischer G Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure N Engl J Med Dec 9
2010 363(24) 2320ndash2331
bull Jones HE OrsquoGrady KE Malfi D Tuten M Methadone maintenance vs methadone taper during pregnancy maternal and neonatal outcomes Am J Addict 200817372ndash86
bull Jarvis MA Schnoll SH Methadone treatment during pregnancy Journal of Psychoactive Drugs 199426(2) 155ndash61
bull Kaltenbach K Berghella V Finnegan L Opioid depen- dence during pregnancy Effects and management Obstet Gynecol Clin North Am 199825139ndash51
bull Kesmodel U Kesmodel KS Larsen A Secher NJ Use of alcohol and illicit drugs among pregnant Danish women 1998 Scand J Public Health 200331(1)5-11
bull Ludlow JP Evans SF Hulse G Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse Australian and New Zealand Journal of Obstetrics and Gynaecology 200444(4)301ndash6
bull Keyes KM Grant BF Hasin DS Evidence for a closing gender gap in alcohol use abuse and dependence in the United States population Drug Alcohol Depend 20089321-9
bull Luty J Nikolaou V Bearn J Is opiate detoxification unsafe in pregnancy Journal of Substance Abuse Treatment 2003 24363-7
bull Marquet P Chevrel J Lavignasse P et al Buprenorphine withdrawal syndrome in a newborn Clin Pharmacol Ther 1997 62569-571
bull McCarthy JJ Intrauterine abstinence syndrome (IAS) during buprenorphine inductions and methadone tapers can we assure the safety of the fetus Journal of Maternal-Fetal amp Neonatal Medicine 2012 25109-
12
bull McElhatton PR The effects of benzodiazepine use during pregnancy and lactation Reprod Toxicol 1994 Nov-Dec8(6)461-75)
bull Montgomery A Hale TW and Academy Of Breastfeeding Medicine ABM Cinical Protocol 15 Analgesia and Anesthesia For the Breastfeeding Mother Revised 2012 Breastfeed Med 2012 7(6)547-53
bull Morse B Gehshan S and Hutchins E Screening for Substance Abuse During Pregnancy Improving Care Improving Health National Center for Education in Maternal and Child Health 1997
bull NICE clinical guidelines Available on httpwwwniceorguknicemedialive119474011540115pdf
bull Patra J Bakker R Irving H Jaddoe VWV Malini S Rehm J (2011) Dose- response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight preterm birth and small
for gestational age (SGA)mdasha systematic review and meta-analyses BJOG 1181411ndash1421
bull Plessinger MA Prenatal exposure to amphetaminesrisks and adverse outcomes in pregnancy Obstet Gynecol Clin N Am 25 (1998) 119-138)
bull Product Information VIVITROL(R) extended-release injectable suspension naltrexone extended-release injectable suspension Alkermes Inc Waltham MA 2010
bull Randall CL Roberts JS Del Boca FK et al Telescoping of landmark events associated with drinking a gender comparison J Stud Alcohol 199960252-60
bull Rawson RA Marinelli-Casey P Anglin MD Dickow A Frazier Y Gallagher C et al A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence Methamphetamine
Treatment Project Corporate Authors Addiction 200499708ndash17
bull Rayburn W Bogenschutz MP Pharmacotherapy for pregnant women with addiction American Journal of Obstetrics and Gynecology 20041911885ndash97
References bull Rehm J Baliunas D Borges GLG Graham K Irving H Kehoe T Parry CD Patra J Popova S Poznyak V Roerecke M Room R Samokhva- lov AV Taylor B (2010) The relation between different dimensions of
alcohol consumption and burden of disease an overview Addiction 105817ndash843
bull Reis et al Combined use of selective serotonin reuptake inhibitors and sedativeshypnotics during pregnancy risk of relatively severe congenital malformations or cardiac defects A register study BMJ Open
20133e002166
bull Rementeria JL Nunag NN Narcotic withdrawal in pregnancy stillbirth incidence with case report Am J Obstet Gynecol 1973 Aug 15116(8)1152-6
bull Roll JM Petry NM Stitzer ML Brecht ML Peirce JM McCann MJ et al Contingency management for the treatment of methamphetamine use disorders Am J Psychiatry
20061631993ndash9
bull Russell M Martier SS Sokol RJ Mudar P Bottoms S Jacobson S Jacobson J Screening for pregnancy risk-drinking Alcohol Clin Exp Res 199418(5)1156-61
bull Saladin ME Gray KM Carpenter MJ et al Gender differences in craving and cue reactivity to smoking and negative affectstress cues Am J Addict 201221210-20
bull Sokol RJ Martier SS Ager JW The T-ACE questions practical prenatal detection of risk-drinking Am J Obstet Gynecol 1989160863ndash8
bull Smith LM LaGasse LL DeRauf C et al the infant development environment and lifestyle study Effects of prenatal methamphetamine exposure polydrug exposure and poverty on intrauterine growth
Pediatrics 118(2006)1149-1156
bull Terplan M McNamara EJ Chisolm MS Pregnant and non-pregnant women with substance use disorders The gap between treatment need and receipt Journal of Addictive Diseases 201231342-9
bull Tharner A Luijk MP Raat H Ijzendoorn MH Bakermans-Kranenburg MJ Moll HA et al Breastfeeding and its relation to maternal sensitivity and infant attachment J Dev Behav Pediatr 2012 33 396ndash404
bull Uziel-Miller N Dresner N Addressing substance use in obstetrics and gynecology Prim Care Update OB Gyn 9(2002)98-104
bull Waal H Is sustained release natrexone an option for heroin- dependent pregnant women Addiction 2013 108 252ndash3
bull Welle-Strand GK Skurtveit S Jones HE Waal H Bakstad B Bjarkoslash L Ravndal E Neonatal outcomes following in utero exposure to methadone or buprenorphine a National Cohort Study of opioid-agonist
treatment of Pregnant Women in Norway from 1996 to 2009 Drug Alcohol Depend 2013 Jan 1127(1-3)200-6 Epub 2012 Jul 25
bull White J Blocking endogenous opioids during development--do we understand the consequences Addiction 2013 Feb108(2)251-2
bull Williams JF Smith VC Fetal Alcohol Spectrum Disorders Pediatrics136(5) November 2015 e1395-e1406
bull Winklbaur B Kopf N Ebner N Jung E Thau K Fischer G Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence a knowledge synthesis for better
treatment for women and neonates Addiction 20081031429ndash40
bull World Health Organization Guidelines for the Psychosicially Assisted Pharmacological Treatment of Opioid Dependence Geneva Switzerland WHO Press 2009
bull Zierler S Rothman KJ Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy N Engl J Med 1985313347ndash52
bull Zuspan FP Gumpel JA Mejia-Zelaya A Madden J Davis R Fetal stress from methadone withdrawal Am J Obstet Gynecol 1975 May 1122(1)43-6
![Pregnancy Workbook - Arizona State University · 2016-07-20 · Substance Abuse Summit. ... Dependency During Pregnancy Workbook] 2. Extension for Community Health Care Outcomes (ECHO)](https://img.dokumen.tips/doc/110x75/5fa87ef03ad2947084077c4a/pregnancy-workbook-arizona-state-university-2016-07-20-substance-abuse-summit.jpg)
