Marijuana use in pregnancy and lactation: a review …...Marijuana use in pregnancy and lactation: a review of the evidence Torri D. Metz, MD, MS; Elaine H. Stickrath, MD M arijuana

ajog.org Obstetrics Expert Reviews

Marijuana use in pregnancy and lactation:a review of the evidenceTorri D. Metz, MD, MS; Elaine H. Stickrath, MD

arijuana is the most frequently

With the legalization of recreational marijuana in many states, we anticipate more womenwill be using and self-reporting marijuana use in pregnancy. Marijuana is the mostcommon illicit drug used in pregnancy, with a prevalence of use ranging from 3% to 30%in various populations. Marijuana freely crosses the placenta and is found in breast milk.It may have adverse effects on both perinatal outcomes and fetal neurodevelopment.Specifically, marijuana may be associated with fetal growth restriction, stillbirth, andpreterm birth. However, data are far from uniform regarding adverse perinatal outcomes.Existing studies are plagued by confounding by tobacco and other drug exposures as wellas sociodemographic factors. In addition, there is a lack of quantification of marijuanaexposure by the trimester of use and a lack of corroboration of maternal self-report withbiological sampling, which contributes to the heterogeneity of study results. There is anemerging body of evidence indicating that marijuana may cause problems with neuro-logical development, resulting in hyperactivity, poor cognitive function, and changes indopaminergic receptors. In addition, contemporary marijuana products have higherquantities of delta-9-tetrahydrocannabinol than in the 1980s when much of the mari-juana research was completed. The effects on the pregnancy and fetus may therefore bedifferent than those previously seen. Further research is needed to provide evidence-based counseling of women regarding the anticipated outcomes of marijuana use inpregnancy. In the meantime, women should be advised not to use marijuana in preg-nancy or while lactating.

Key words: cannabis, lactation, marijuana, pregnancy

M used illicit drug in Westerncountries.1 In 2013, 19.8 million, or7.5% of the US population, reported itsuse within the last month, an increasefrom 2007 when only 5.8% of the pop-ulation had used marijuana within thepast month.2,3

Reported prevalence rates of mari-juana use in pregnancy vary from as lowas 3% to as high as 34%.4,5 We anticipatean increase in marijuana use in preg-nancy as legalization of marijuana in-creases throughout the United States.This review is intended to providepracticing clinicians with an under-standing of existing literature and rec-ommendations for managing womenwho use marijuana during pregnancybecause this will be an increasinglyencountered clinical scenario.

The term marijuana is usedthroughout this article to representcannabis use globally. Technically theactive psychogenic component of mari-juana is a cannabinoid called delta-9-tetrahydrocannibinol (THC).6

Search methodologyOvid Medline (PubMed) and Embasewere searched on Dec. 11, 2014, for rele-vant articles. A focused search was con-ducted with the search terms marijuanaand marihuana or cannabinoids andpregnancy, lactation, and outcomes

From the Denver Health Medical Center,Department of Obstetrics and Gynecology,Denver, CO (Drs Metz and Stickrath), andUniversity of Colorado School of Medicine,Aurora, CO (Drs Metz and Stickrath).

Received March 12, 2015; revised May 5, 2015;accepted May 13, 2015.

The authors report no conflict of interest.

Corresponding author: Torri Metz, MD, [email protected]

0002-9378/$36.00ª 2015 Elsevier Inc. All rights reserved.http://dx.doi.org/10.1016/j.ajog.2015.05.025

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including adverse perinatal outcomes andneurodevelopment. A search without anylanguage or year limits yielded 615 uniquecitations. Abstracts were reviewed by theauthors, and all pertinent articles wereobtained and reviewed individually. Inaddition, references of pertinent articleswere reviewed to find any additionalarticles that were not identified with theinitial search (n ¼ 43). All pertinent arti-cles are summarized here. Our goal wasnot to provide a systematic review of aspecific research question but rather toprovide practicing clinicians with acomprehensive overview of the existingmarijuana in pregnancy and lactationliterature.

Legalization of marijuanaCurrently both recreational and medicalmarijuana remain illegal by federal lawin the United States. However, thelegalization of medical and recreationalmarijuana at the state level is increasing

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throughout the United States. At thispoint, 23 states have legalized the use ofmedical marijuana, and 4 states havelegalized both medical and recreationalmarijuana (Figure).

The Colorado experienceMedical marijuana was legalized inColorado in the year 2000. However, itwas not until 2009 when the US AttorneyGeneral issued a statement passing thejurisdiction of marijuana law enforce-ment to state governments that we saw asharp increase in the number of medicalmarijuana users in the state.7 In 2012,recreational marijuana was legalizedin the state of Colorado with the passingof Amendment 64. There is no stipula-tion in the law stating that pregnantwomen cannot purchase or possessmarijuana.

Sales of recreational marijuana havebeen steadily increasing since the openingof the first recreational dispensaries on

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FIGUREAn increasing number of states in the United States have legalized bothmedicinal and recreational marijuana use

Metz. Marijuana in pregnancy. Am J Obstet Gynecol 2015.

Expert Reviews Obstetrics ajog.org

Jan. 1, of 2014. The state of Colorado doesnot publish overall sales amounts butdoes publish tax revenue on a monthlybasis. In January 2014, the revenue was3.5 million dollars. The monthly taxrevenue is now up to 7.6 million dollarsfor the month of October 2014, showinga steady increase in sales and consump-tion.8 In addition, there has been an in-crease in the use of alternative forms ofconsumption such as vaping (heating thecannabis to release THC and cannabi-noids without making it smoke), lotions,and edibles.7,9

Following the legalization of mari-juana, we have noted several unantici-pated adverse consequences of theincrease in marijuana availability inclu-ding an increase in pediatric overdosesand emergency visits for marijuanatoxicity.7

Attitudes and beliefsWhen women have been followed uplongitudinally during pregnancy, a de-crease in marijuana use has been notedacross trimesters of pregnancy. In a 1 year

762 American Journal of Obstetrics & GynecologyDown

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prospective cohort study, marijuana usein pregnancy declined from 32% in thefirst trimester to 16% in the thirdtrimester.5

Similarly, a longitudinal prospectivestudy on drug use in pregnancy (n¼ 86),the Development and Infancy Study,found that the percentage of womenwhoused marijuana throughout the preg-nancy declined. However, approximately60% of women who used marijuana inthe year prior to pregnancy continued touse more than 10 joints per week, indi-cating that many women continue usethroughout pregnancy.10 It should benoted that the women in the Develop-ment and Infancy Study10 smoked anaverage of 21 joints per week in themonth prior to pregnancy and may notbe representative of less frequent users ofmarijuana.Two thirds of adults surveyed in a UK

study noted that cannabis was either“not very harmful” or “not at all harm-ful.”11 This is in contrast to other recre-ational drugs such as heroin or cocainein which less than 5% of adults surveyed

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perceived them to be either “not veryharmful” or “not at all harmful.”11

The perceived safety likely contributesto the high prevalence of its use inpregnancy.

Screening and testing for marijuanauseThe American College of Obstetriciansand Gynecologists and the AmericanAcademy of Pediatrics support screeningall women for drug use at the time ofentry to prenatal care.12 Verbal screeningfor self-reported use was noted to beacceptable to patients in one study.13

Women who report use should thenbe encouraged to stop and referred tolocal substance use disorder programs ifneeded.

Unfortunately, maternal and fetaltesting for marijuana exposure is fraughtwith error.14Maternal urine testing is themost accurate method of testing. How-ever, the duration of a positive urinetoxicology result from the last use de-pends on many factors including chro-nicity of use (Table 1). Despite itslimitations, urine is easy to obtain, hasa high concentration of metabolites, andis therefore the preferred method ofscreening.6

Testing of maternal hair samples isinaccurate and may remain positivedespite no recent use. Neonatal hair andmeconium can also be tested (Table 1);however, because of the cost of testing,delay in results, and a high false-positiverate in laboratory testing of meconiumby different techniques,15 neonataltesting is rarely used in clinical practice.

There are no goodmethods to quantifythe amount of marijuana ingested usingbiological sampling in a clinical setting.The amount of THC in various forms ofmarijuana varies by the extraction pro-cess from the plant, Cannabis sativa,which also results in challenges in quan-tifying self-reported use. In addition, thevarious forms of consumption result indifferent rates of absorption and peakblood concentrations.7 In a report fromthe University of Mississippi’s PotencyMonitoring Project, the average concen-tration of THC in seized samples in theUnited States in 2008 was 13.0%, whichwas an increase from 3.2% in 1983.16

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TABLE 1Testing for marijuana in biological samplesBiologicalsample Duration of positive result Test limitations

Maternal urine 2e3 days in occasional users63

Several weeks in chronic users64Chronicity of use determines durationof positive result63

Maternalserum

2e3 days in occasional users6

Several weeks in chronic users6Chronicity of use determines durationof positive result63

Invasive sampleShorter half-life than urine6

Maternal hair Several weeks65 Less accurate for marijuana thanother drugs65

False positives from passiveexposure65

Not clinically used due to cost andinaccuracy

Meconium Positive result indicatessecond- and third-trimesterexposure26,66,67

Small amount of detectable THCin the samples68

High false-positive rate (up to 43%)15

Send out to reference laboratoryCostly and impractical at many sites

Neonatal hair Positive result indicatesthird-trimester exposure66

Costly and impractical at many sitesLess sensitive than meconium66

THC, delta-9-tetrahydrocannibinol.



Nausea and vomiting in pregnancyAs with any drug or medication inpregnancy, possible benefits must beweighed against possible adverse effects.There are few data on the possible ben-efits of marijuana use in pregnancy. In-terest in the use of marijuana as anantiemetic has been propagated by itsefficacy in oncology patients.17,18

There are 2 studies investigating therelationship between marijuana use andnausea and vomiting of pregnancy.19,20

Roberson et al20 used the pregnancyrisk assessment monitoring system data(n ¼ 4375) and found that women whoused marijuana in pregnancy were morelikely to report severe nausea (3.7% vs2.3%; prevalence ratio, 1.63; 95% con-fidence interval [CI], 1.08e2.44). Thetreatment of nausea with marijuana wasnot specifically addressed in the study.

Westfall et al19 reported on the prev-alence of nausea among 79 women whoused medicinal marijuana in pregnancy.Forty of these women (51%) usedmarijuana to treat nausea and vomitingof pregnancy, and 92% of them believedit was effective. There was no controlgroup, no documentation of quantityused, or a demonstration of effect onsymptoms of nausea other than subjec-tive report by survey after the pregnancy.

In summary, the effect of marijuanause on nausea and vomiting of preg-nancy is unknown.

Anesthetic considerationsMarijuana use can affect the safety andadministration of anesthesia surroundingdelivery. In high doses, marijuana cancause bradycardia and hypotension, butmore commonly, low or moderate dosescan cause tachycardia.21 If tachycardia ispresent or marijuana use is suspected,drugs that increase heart rate such asketamine, pancuronium, and epineph-rine should be avoided. Because mari-juana is often inhaled, it can also causeupper-airway irritation and edema,making anesthetic administration morecomplicated.21

Adverse perinatal outcomesFetal growthMany of the human studies of marijuanain pregnancy focus on fetal growth


(Table 2).4,22-35 Abnormalities in growthare biologically plausible, given the pas-sage of cannabinoids across the placenta.There are some data suggesting thatcannabis affects glucose and insulinregulation and therefore may affect thefetal growth trajectory.25 However, dataregarding fetal growth with marijuanaexposure are mixed, with some studiesdemonstrating a decrease in birthweightand/or growth and others demon-strating no association (Table 2). In part,the controversy may be a result ofdiffering methodology for the ascer-tainment of marijuana exposure, varyingfrom a single question about self-reported use at study entry to detailedlongitudinal frequency of use data andbiological sampling (Table 2). In addi-tion, many early studies did not accountfor concurrent exposure to tobacco.36

A metaanalysis by English et al36

(1997) focused on the association be-tween marijuana exposure and birth-weight. This metaanalysis included 10studies in which the investigatorsadjusted for the effect of tobacco expo-sure. Whereas women who consumed

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large quantities of marijuana (more than4 times per week) had babies thatweighed less than nonusers by 131 g onaverage, the pooled odds ratio for lowbirthweight with any marijuana use was1.09 (95% CI, 0.94e1.27).36

Most of the trials included in themetaanalysis utilized self-report ofmarijuana use as the predictor of lowbirthweight rather than biological sam-pling. Zuckerman et al35 found anassociation between a positive urinetoxicology screen for THC and lowerbirthweight (79 g decrease in birth-weight, P ¼ .04). However, there was noobserved association when only self-report was considered. These authorsargued that a lack of association betweenmarijuana and lower birthweight inother studies may have been a result ofincomplete ascertainment of exposureby relying on self-report.35

There is only one study, a secondaryanalysis of the Generation R data (a largeprospective trial to assess early environ-mental and genetic determinants ofhealth in The Netherlands), in whichserial ultrasounds were performed to

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TABLE 2Summary of marijuana and fetal growth restriction studies

Study and numberin cohort

Marijuana-exposedwomen, n (%) Setting Data source Marijuana measure

Other variablesconsidered inanalysis

Findings (adjusted ORs orregression coefficientswith 95% CIs reportedwhen available)

Limitations andcomments

Prospective cohort studiesa

Day et al, 199132

(n ¼ 519)324 (62) Single institution Self-report by

prenatal interviewin each trimesterof pregnancy

Frequency: light(0e2.9 joints/wk),moderate (3e6.9/wk),and heavy(�1 joints/d)

SES, obstetric hx,medical hx, standarddemo, other drugs,EtOH, tobacco

No association with SGAIsolated higher birthweightin heavy third-trimesterusers compared withnonusers (3357 g vs3215 g; P ¼ .04)

Increase in birthweightin marijuana userscompared with nonusersWomen who usemarijuana wereintentionallyoversampled

El Marroun et al,200925 (n ¼ 7452)

459 (6) Population-basedstudy in TheNetherlands

Self-report at studyenrollment

Frequency: daily,weekly, monthlyReported use: onlybefore pregnancy, usein early pregnancy, orongoing use

Standard demo,psych hx, EtOH, fetalsex, tobaccoExcluded women withother drugs

Use before pregnancy didnot affect growthEarly pregnancy usedecreased growth 11.18 g(e15.26 to e7.10)/wkOngoing marijuana usedecreased growth 14.44 g(e22.94 to e5.94)/wk

Only study with serialultrasounds to assessfetal growth (detailed infetal growth section oftext)Marijuana use not wellquantified

Fergusson et al,200222

(n ¼ 12,129)

606 (5) Population-basedstudy in UnitedKingdom

Self-completedquestionnaire at18e20 wksgestation

Frequency: 1 time/day, 2e4 time/wk, 1time/wk, <1 time/wkbefore pregnancy, firsttrimester and ongoing

Standard demo, otherdrugs, EtOH, tobacco

Ongoing use 1 or more/wkthroughout pregnancy wasnot associated with lowerbirthweight e84.20 g(e174.70 to 6.40)

Self-report data collectedat 18e20 wks’ gestation,no later pregnancy data

Fried et al, 198433

(n ¼ 583)84 (14) Referred to study by

primaryobstetrician/studyads

Self-report byprenatal interviewin each trimesterof pregnancy

Frequency: irregularusers (�1 joint/wk),moderate (2-5/wk),heavy (>5/wk)

SES, OB hx, medicalhx, standard demo,other drugs, EtOH,tobacco

No association withLBW

Marijuana use not wellquantified, averaged overthe course of pregnancy

Gray et al, 201026


prenatal interviewin each trimesterof pregnancyBiological samples

Frequency: number ofjoints/day by trimesterPresence of THC inmaternal saliva andmeconium

Standard demo, OBhx (parity only),tobaccoExcluded women withother drugs, or heavyEtOH

THC in meconiumassociated with lowerbirthweight (3429 g vs2853 g; P < .001),persistent effect inmultivariable logisticregressionSelf-report alone wasnot associated withlower birthweight

Study designed to assesstobacco exposureprimarilySampling strategy forhigh prevalence of usenot reported

Metz. Marijuana in pregnancy. Am J Obstet Gynecol 2015. (continued)

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TABLE 2Summary of marijuana and fetal growth restriction studies (continued)






Hatch et al,198669 (n¼ 3857)

366 (10) Planned delivery atsingle institution

Self-report bystructured interviewearly in pregnancy

Frequency: none,occasional (�1 times/mo), regular (�2times/mo)

OB hx, standarddemo, other drugsEtOH, tobacco

Regular use in whitewomen associated withLBW (OR, 2.6; 95%CI, 1.1e6.2)Regular use in whitewomen associated withSGA (OR, 2.3; 95% CI, 1.3e4.1)

Self-report data collectedearly in pregnancy, nolater pregnancy dataDiffering results by racialgroupMarijuana use not wellquantified

Hingson et al,198234 (n ¼ 1690)

237 (14) Single institution Self-report bystructured interviewpostpartum

Frequency: <1time/mo, <1/wk,1e2 times/wk, �3per week


Neonates 95 g smaller thannonusers with use <3times/wk (P < .01)Neonates 139 g smallerthan nonusers with use�3times/wk (P < .01)

Possible recall bias, mostexposure data collectedpostpartum, small subsetwith prenatal interview(n ¼ 328)Marijuana use not wellquantified

Hurd et al, 200527

(n ¼ 139)44 (32) Women undergoing

elective terminationat a single center at17e22 wks

Self-report bystructured interviewat time of terminationBiological samples

Frequency: light(0e0.4 joints/d),moderate (0.41e0.88/d), and heavy(�0.89 joints/d),THC in maternal urineor meconium

Standard demo,gestational age attermination, EtOH,tobaccoExcluded womenwith cocaine/opiates

Increasing self-reporteduse not associated withdecreasing weightDecreased birthweight inmarijuana-exposed (eitherurine/meconium positivetoxicology or self-report)fetuses by 14.53 g (e28.21to e0.86)

Growth assessed inmidgestation prior topresentation of mostgrowth abnormalitiesWomen in study wereundergoing electivetermination of pregnancy

Kliegman et al,199470 (n ¼ 425)

34 (8) Single institution Self-report bystructured interviewat time of deliveryBiological samples

THC in maternal urineat time of delivery

SES, OB hx, standarddemo, other drugs,EtOH, tobacco

No association with LBW(OR, 2.28; 95%CI, 0.27e19.5)

Study designed to assesscocaine exposureprimarilyMarijuana use notquantified

Linn et al, 198371

(n ¼ 12,424)1246 (10) Single institution Self-report by

structured interviewpostpartum

Frequency:occasional, weeklyor daily use


No association with LBWfor any use of marijuana(OR, 1.07; 95%CI, 0.87e1.31)

Possible recall bias,exposure data collectedpostpartumMarijuana use not wellquantified


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Tennes et al,19855 (n ¼ 756)

257 (34) Two affiliatedinstitutions

Self-report bystructured interviewat 1 prenatal visit andpostpartum

Frequency quantifiedby trimester: light (�1times/wk), moderate(>1 time/wk but <1time/d), heavy (�1times/d)


No effect on birthweightwhen considered bytrimester or as a totalamount consumed duringpregnancy

Possible recall bias, only2 sessions of self-report,which was then reportedby trimester of useMarijuana use not wellquantified

Zuckerman et al,198935 (n ¼ 1226)

331 (27) Single institution Self-report bystructured interviewat 1 prenatal visit andpostpartumBiological sampling

Reported use: yes/noTHC in maternal urineat time of prenatal orpostpartum interview


Positive urine toxicologyscreen for THC associatedwith 79 g decrease inbirthweight (P ¼ .04)No association when onlyself-report considered

Possible recall bias, only2 sessions of self-reportMarijuana use not wellquantified

Secondary analysis of prospective cohorta

Bada et al, 200528

(n ¼ 8637)812 (9) Multicenter, 4

university-basedcenters

Self-report bystructured interviewprior to delivery

Reported use:yes/no


No association with LBW(OR, 1.08; 95% CI, 0.85e1.36) or SGA (OR, 0.9;95% CI, 0.73e1.11)

Not designed to assessmarijuana specifically(Maternal LifestyleStudy72)Marijuana use notquantified

Gibson et al,198373 (n ¼ 7301)


Self-report bystructured interviewat 1 prenatal visit andpostpartum

Frequency: �1 times/wk, >1 time/wk

Standard demo, OBhx (parity only), EtOH,tobacco

No association with LBWafter excluding prematureneonates

Marijuana use not wellquantified

Janisse et al,201429 (n ¼ 3090)

748 (24) Single institution Self-report bystructured interviewat each prenatal visit

Proportion of prenatalvisits with reporteduse: 1e33%,34-66%, or 67-100%


55 g decrease in fetalgrowth with ongoingmarijuana use (reported at67e100% of visits)(P < .004)

Study designed to assessEtOH exposurePopulation limited toAfrican AmericansMarijuana use not wellquantified


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Kline et al, 198774

(n ¼ 2815)275 (10) Two overlapping

prospective cohortsat 3 urban hospitals

Self-report bystructured interviewat 1 prenatal visit

Frequency: <1 time/mo,2e3 times/mo,2e3 times/wk, 4e6times/wk, daily


No association with FGR inearly cohortDecreased growth withincreased use (127 g lesswith 2e3 times/wk, 143 gless with 4e6 times/wkand 230 g less with daily) inlate cohort

Study designed as acase-control study withSAB as primary outcomeDiffering results for 2overlapping prospectivecohortsMarijuana use not wellquantified

Saurel-Cubizolleset al, 20144

(n ¼ 13,545)

156 (1) Population-basedstudy, all births inFrance during asingle week

Self-report bystructured interview2e3 d postpartum

Frequency: <1 time/mo, 1e9 times/mo,�10 times/mo

SES, standard demo,EtOH, tobacco

No association with SGAfor <1 time/mouse (OR, 1.29; 95% CI, 0.61e2.72) or for use �1times/mo use comparedwith nonusers (OR, 1.30;95% CI, 0.66e2.56)Also no association withSGA for non-tobacco users,marijuana only

Recall biasLow prevalence of useconcerning forascertainment bias formarijuana exposureMarijuana use not wellquantified

Shiono et al,199540 (n ¼ 7470)

822 (11) Multicenter, 7university-basedclinics

Self-report bystructured interviewat 1 prenatal visitBiological samples

Frequency: numberof times/wkTHC in maternalserum


No association with LBWwhen marijuana useassessed by self-report orpositive serum assay forTHC (OR, 1.1; 95%CI, 0.9e1.5)Increased odds of LBWwith positive serum assayin isolation but not withself-report

Study designed to assessassociation betweenvaginal infectionsand PTBMarijuana use not wellquantified

Teitelman et al,199075 (n ¼ 1206)

95 (8) Planned delivery atsingle institution

Self-report bystructured interviewearly in pregnancy

Reported use:yes/no

OB hx, standarddemo, other drugs,EtOH, tobacco

No association with LBW(OR, 1.57; 95%CI, 0.54e4.52)

Study designed to assessassociations betweenmaternal work activityand LBWSame cohort as Hatchet al69 study withdifferent inclusion criteria(employed women)No quantification ofmarijuana use


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TABLE

2Sum

maryof

marijuanaandfetalg

rowth

restrictionstudies(continued)

Study

andnu

mber

incohort

Marijuana-exposed

wom

en,n

(%)

Setting

Datasource

Marijuanameasure

Other

variables

considered

inanalysis

Find

ings

(adjustedORsor

regression

coefficients

with95%

CIsreported

whenavailable)

Limitations

and

comments

vanGelderetal,

2010

30(n¼5871)189(3)

Population-based,

USNationalB

irth

DefectsPrevention

Study

Self-reportby

structured

interview6

wks

to24

moafter

delivery

Reporteduse:yes/no

bytrimester

SES,OBhx,medical

hx,standard

demo,

otherdrugs,EtOH,

tobacco

Noassociationwith

LBW

(OR,0.7;95%

CI,0.3e

1.6)

Nodifference

inmean

birthw

eight(e17

g;P¼

.65)

Nodifference

bytrimester

ofuse

Recallbias,interviewsup

to2yearspostpartum

Notdesigned

for

marijuanaexposure

specifically

(birthdefects

registry)

Marijuanausenotwell

quantified

CI,confidenceinterval;EtOH,alcoholuse;FGR,fetalgrow

threstriction(estimated

fetalweightlessthan

the10thpercentile);LBW,low

birthw

eight(defined

<2500

gunlessotherwisenoted);M

edicalhx,m

edicalhistory;OBhx,obstetricalhistory;OR,oddsratio;PTB,

pretermbirth(<37

weeks);SAB,spontaneous

abortion;SES,socioeconomicstatus;SGA,smallforgestationalage

(birthw

eightlessthan

the10thpercentile);Standarddemo,somemeasureofstandarddemographicsincludingmaternalage,race,body

massindex;

THC,delta-9-tetrahydrocannabinol.

aStudiesthatdidnotadjustfortobaccouseandretrospectivecohortsarenotincluded

inthissummarytable.

Metz.Mariju

anain

pregnancy.Am

JObstetGynecol2015.


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assess fetal growth rather than usingbirthweight as the outcome.25 Womenwere followed up prospectively withgrowth ultrasounds at less than 18weeks, 18-25 weeks, and 25 weeks orlonger. Marijuana exposure data were byself-report. Fetuses exposed to mari-juana in early pregnancy (n¼ 214) grew11.2 g/wk less than the nonusers, andthis effect was more pronounced inwomen with continued use throughoutpregnancy (Table 2). The long-term ef-fects of this small growth decrement areunknown.

A small subset of the Generation Rcohort had Doppler ultrasound scansperformed between 28 and 34 weeks.37

Women with cannabis use in early preg-nancy (n¼ 14) and womenwith ongoingcannabis throughout pregnancy (n ¼ 9)were compared with nonusers. There wasno difference in the umbilical arterypulsatility index or fetal cerebral bloodflow. Women who used cannabisthroughout pregnancy had a higheruterine artery pulsatility index and resis-tance index than nonusers after adjustingfor fetal weight, fetal sex, and maternaleducation. The authors appropriatelycautioned against drawing widespreadconclusions from these data, given thesmall sample size.

It should be noted that in contrast toall other studies finding a small growthdecrement or no difference in birth-weight, one prospective study noted anincrease in birthweight among neonatesexposed to heavy use of marijuana (morethan 1 joint/day) in the third trimester(3357 g v 3215 g; P¼ .04).32 This findinghas not been replicated in any otherstudies and was not demonstrated withuse in other trimesters.

In summary, there may be a smalldecrease in growth with exposure tomarijuana in pregnancy. However, theclinical significance of this decrease isquestionable, with reported growth dif-ferences on the order of 100 g.

StillbirthMany of the prior studies of marijuana inpregnancy exclude women with a still-birth, so data regarding stillbirth andmarijuana use are scant. However, arecent case-control study by Varner et al38


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TABLE 3Summary of marijuana and preterm birth studies


Marijuana- exposedwomen, n, %

Study design andsetting Data source Marijuana measure


Findings (adjusted ORswith 95% CIs reportedwhen available)


Prospective cohorta

Day et al, 199132


prenatal interview ineach trimester ofpregnancy

Frequency: light(0e2.9 joints/wk),moderate (3e6.9/wk),and heavy (�1 joints/d)


No effect on length ofgestationNo association with PTB

Women who usemarijuana wereintentionallyoversampled

Dekker et al,201439

(n ¼ 3184)

213 (7) withpre-pregnancyexposure

Internationalmulticenter

Self-report bystructured interviewsat 20 wks

Timing of use: beforepregnancy, firsttrimester


Prepregnancy useassociated withspontaneous PTB withintact membranes(OR, 2.34; 95%CI, 1.22e4.52)

Study designed todevelop screeningtests for PTB andother adverseobstetrical outcomesMarijuana use notquantified

Fried et al, 198433

(n ¼ 583)84 (14) Referred to study by

primary obstetrician/study ads

Self-report byprenatal interview ineach trimester ofpregnancy

Frequency: irregularusers (�1 joints/wk,moderate (2e5joints/wk), heavy(>5 joints/wk)


Heavy use of marijuanareduced the length ofgestation by 0.8 wks(P ¼ .008)Increasing useassociated withdecreasing length ofgestation

Marijuana use notwell quantified bytrimester, averagedover the course ofpregnancy

Hatch et al, 198669

(n ¼ 3857)366 (10) Planned delivery at

single institutionSelf-report bystructured interviewearly in pregnancy

Frequency: none,occasional (�1times/mo), regular(�2 times/mo)

OB hx, standarddemo, other drugsEtOH, tobacco

Use associated withincreased rate of PTB(<37 wks) in whitewomen (OR, 1.9; 95%CI, 1.0e3.9)No association with PTBin women of other races

Marijuana use notwell quantified,especially for morefrequent usersSelf-report datacollected early inpregnancy, no laterpregnancy data

Kliegman et al,199470 (n ¼ 425)

34 (8) Single institution Self-report bystructured interviewat time of deliveryBiological samples

THC in maternal urineat time of delivery

SES, OB hx, standarddemo, other drugs,EtOH, tobacco

No association with PTB(OR, 1.89; 95%CI, 0.34e10.50)

Study designed toassess cocaineexposure primarilyMarijuana use notquantified


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TABLE 3Summary of marijuana and preterm birth studies (continued)





F dings (adjusted ORsw h 95% CIs reportedw en available)


Linn et al, 198371

(n ¼ 12,424)1246 (10) Single institution Self-report by

structured interviewpostpartum

Frequency:occasional, weekly,or daily use


N association with PTB( , 1.02; 95%C 0.82e1.27)

Possible recall bias,exposure datacollected postpartumMarijuana use notwell quantified

Tennes et al,19855 (n ¼ 756)


Self-report bystructured interviewat 1 prenatal visitand postpartum

Frequency quantifiedby trimester: light(�1 times/wk),moderate(>1 time/wk but<1 times/d), heavy(�1 times/d)


N odds ratio reported forP (0% PTB rate in �3t es/wk users and 7%in onusers)T al marijuana use inp gnancy positivelyc related with increasedg tational age at birth( 0.10), average of 2d nger gestation withd ly use

Possible recall bias,only 2 sessions ofself-reportNo PTB (0%) in thenonusers ascomparison groupFinding of longerlength of gestationnot replicated in otherhuman studies

Secondary analysis of a prospective cohorta

Bada et al, 200528

(n ¼ 8637)812 (9) Multicenter, 4

university-basedcenters

Self-report bystructured interviewprior to delivery

Reported use: yes/no SES, OB hx, medicalhx, standard demo,other drugs, EtOH,tobacco

N association with PTB( , 1.21; 95%C 0.9e1.61)

Not designed toassess marijuanaspecifically (MaternalLifestyle Study72)Marijuana use notquantified

Gibson et al,198373

(n ¼ 7301)


Self-report bystructured interviewat 1 prenatal visitand postpartum

Frequency: �1 times/wk, >1 time/wk

Standard demo, OBhx (parity only), EtOH,tobacco

H h proportion of PTBa ong >1 time/wku rs (25% vs 6% inn users; P < .001)

Marijuana use notwell quantified

Janisse et al,201429 (n ¼ 3090)

748 (24) Single institution Self-report bystructured interviewat each prenatal visit

Proportion of prenatalvisits with reporteduse: 1e33%,34e66%, or67e100%


N associated with PTB Study designed toassess EtOHexposure primarilyPopulation limited toAfrican AmericansMarijuana use notwell quantified


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TABLE 3Summary of marijuana and preterm birth studies (continued)





F dings (adjusted ORsw h 95% CIs reportedw en available)


Saurel-Cubizolleset al, 20144

(n ¼ 13,545)

156 (1) Population-basedstudy, all births inFrance during a singleweek

Self-report bystructured interview2-3 d postpartum

Frequency: <1 time/mo, 1-9 times/mo,�10 times/month

SES, standard demo,EtOH, tobacco

A marijuana usea ociated withs ntaneous PTB( , 2.15; 95%C 1.10e4.18)N association with PTBw en only women withm rijuana use and noc current tobacco usew re analyzed (OR, 1.22;9 CI, 0.29e5.06)

Recall biasLow prevalence ofuse concerning forascertainment biasfor marijuanaexposureMarijuana use notwell-quantified

Shiono et al,199540

(n ¼ 7470)

822 (11) Multicenter, 7university-basedclinics

Self-report bystructured interviewat 1 prenatal visit,biological samples

Frequency: numberof times per weekTHC in maternalserum


N association with PTBw en marijuana usea essed by self-reporto ositive serum assayf THC (OR, 1.1; 95%C 0.8e1.3)In reased odds of PTBw h positive seruma ay in isolation but notw h self-report

Study designed toassess associationbetween vaginalinfections and PTBMarijuana use notwell quantified

van Gelder et al,201030

(n ¼ 5871)

189 (3) Population-based,US National BirthDefects PreventionStudy

Self-report bystructured interview 6wks to 24 mo afterdelivery

Reported use: yes/noby trimester


N association with PTB( , 1.0; 95%C 0.6e1.9)N difference byt ester of use

Recall bias, interviewup to 2 y postpartumNot designed formarijuana exposurespecifically (birthdefects registry)Marijuana use notwell quantified

CI, confidence interval; EtOH, alcohol use; Medical hx, medical history; OB hx, obstetrical history; OR, odds ratio; PTB, preterm birth (<37 wks); SAB, spontaneous abortion; SES, socioeconomic s us; Standard demo, some measure of standard demographicsincluding maternal age, race, body mass index; THC, delta-9-tetrahydrocannabinol.

a Studies that did not adjust for tobacco use and retrospective cohorts are not included in this summary table.


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in the Stillbirth Collaborative ResearchNetwork demonstrated an increased riskof stillbirth among women who usedmarijuana in pregnancy as demonstratedby THC in the umbilical cord homoge-nate (odds ratio [OR], 2.34; 95% CI,1.13e4.81).

These data are valuable, given theircross-sectional nature, diverse popula-tion, and objectivity. However, there arelimitations including lack of quantifica-tion and timing of marijuana use. Inaddition, the authors noted concern forpossible residual confounding by to-bacco use, which attenuated the asso-ciation between THC in the cordhomogenate and stillbirth by approxi-mately 10%, thereby further stressing theimportance of accounting for concur-rent tobacco use in marijuana research.

Preterm birthData on the association between mari-juana use and preterm birth are mixed,with some studies demonstrating anincreased risk of preterm birth and othersdemonstrating no association (Table 3).This is likely a result of differing meth-odological approaches including poorquantification of marijuana exposureand a lack of documentation of theindication for preterm birth in manystudies (Table 3). Only 2 studies specifyan outcome of spontaneous pretermbirth4,39 rather than a generic outcome ofany preterm birth (<37 weeks).

There are 2, large retrospective,population-based Australian studiessupporting an increased risk of pretermbirth with marijuana use. The first was acohort (n ¼ 24,874) who self-reportedmarijuana use at their intakes for pre-natal care. After adjusting for alcohol,tobacco, and other illicit drugs, mari-juana use was associated with pretermbirth (OR, 1.5; 95% CI, 1.1e1.9).23 Asecond study using International Classi-fication of Diseases, 10th revision, codesfor substance use similarly noted anincreased incidence of preterm birthamong marijuana users (18.8% vs 5.8%;P < .001).24

In contrast, in the Avon LongitudinalStudy of Pregnancy and Childhood,which is a population-based cohortfrom the United Kingdom to study



environmental exposures that affect thehealth and development of children (n¼12,129), the preterm birth rate inwomenwho used marijuana weekly beyond thefirst trimester was exactly the same asnonusers at 4.6% (P ¼ .976).22

One prospective multicenter study byShiono et al40 highlights one of the dif-ficulties in marijuana research. Only31% of the womenwith a positive serumscreen for THC (n ¼ 585) also self-reported use in a structured interview.Conversely, only 43% of women whoself-reported use had a positive serumassay for THC. These investigatorsgrouped women who reported useand/or had a positive drug assay for THCand demonstrated no associationbetween preterm birth and marijuanause (OR, 1.1; 95% CI, 0.8e1.3).40 Therewas, however, an association withpreterm birth in women when only thewomen with a positive serum assay(possibly more chronic users) wereconsidered marijuana exposed (OR, 1.3,95% CI, 1.0e1.7).Multiple other prospective cohort

studies and secondary analyses fail toprovide a definitive answer regardingpreterm birth and marijuana use(Table 3). The majority of studies de-monstrate no increased risk of pretermbirth. However, the 2 studies mentionedin previous text that use spontaneouspreterm birth as the outcome demon-strate an association with marijuanause (Table 3).4,39 Further research withdetailed documentation of obstetricalhistory (specifically history of pretermbirth and risk factors for preterm birth),quantification of marijuana use, andindication for delivery is needed.

Congenital anomaliesThere are 2 studies in which data werecollected prospectively to assess for anassociation of marijuana exposure withcongenital anomalies (Table 4). Neitherof these demonstrated an associationbetween marijuana use and majorcongenital anomalies. There are alsoseveral large retrospective cohort studiesexamining whether there is an associa-tion between marijuana and birth de-fects, with mixed results (Table 4).41-43

Unfortunately, the majority of these


studies are based on birth defects regis-tries with incomplete ascertainment ofconfounding factors and potential forrecall bias with the exposure datacollected long after delivery.

Current evidence does not support anassociation between marijuana exposureand any specific congenital birth defect(Table 4).

NeurodevelopmentThere have been multiple animalstudies and retrospective human studieslooking at the effect of maternalmarijuana use during pregnancy onneurodevelopment, behavior, andintelligence.

Animal studies have shown alterationsin neurotransmitter and neuroendocrinesystems in the offspring of rodentsexposed to cannabinoids. This effectis particularly pronounced withindopaminergic pathways.44 In addition,there have been some animal studies thatshow a marked increase in hyperactivityand exploratory behaviors in femalerats.45 Other rat studies have shownpersistent deleterious effects on learningand memory functions in exposedoffspring.46 Whereas rodent animalstudies cannot be extrapolated directly tohumans, they can help elucidate some ofthe mechanisms by which marijuanaaffects the developing brain.

In human research, there is one pub-lished series of postmortem fetal brains(n ¼ 44) from 17e22 week electiveterminations exposed to marijuana.27

Dopamine receptors were reduced inthe amygdala of marijuana exposed-compared with nonexposed fetuses. Thiseffect was most prominent in male fe-tuses and was directly correlated with theamount of marijuana used during thepregnancy.47

Human research on drug exposure inutero and its subsequent effects is chal-lenging because of confounding psy-chosocial issues and ongoing exposuresthat are impossible to fully adjust for inmultivariable modeling.48 The followingdata must therefore be interpreted withcaution.

One study assessed 26 infants born toadolescent mothers who were exposedto marijuana in utero compared with


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TABLE 4Summary of marijuana and congenital anomalies studies


Marijuana-exposedwomen, n (%)

Study designand setting Data source

Marijuanameasure


Findings (adjustedORs with 95% CIsreported whenavailable)


Any major congenital malformation

Linn et al, 198371

(n ¼ 12,424)1246 (10) Prospective cohort

Single institutionSelf-report bystructuredinterviewpostpartum

Frequency:occasional,weekly, or dailyuse


Rate of major malformation:2.6% nonusers, 3.2%occasional, 3.9% weekly,3.6% dailyNo association with majorcongenital anomalies(OR, 1.36; 95%CI, 0.97e1.91)

Possible recall bias,exposure data collectedpostpartumNo data on trimesterof exposureMarijuana use notwell quantified

Gibson et al, 198373

(n ¼ 7301)392 (5) Secondary

analysisof a prospectivecohortTwo affiliatedinstitutions

Self-report bystructuredinterview at 1prenatal visitand postpartum

Frequency: �1times/wk, >1time/wk

Standard demo,OB hx (parity only),EtOH, tobacco

Rate of major malformation:4.2% in cohort, rates bynonusers and users ofmarijuana not providedNo association withcongenital anomalies,no OR reported

No data on trimesterof exposureMarijuana use notwell quantified

Gastroschisis

Forrester et al, 2007a41

(n ¼ 316,508)829 (0.3) Retrospective

cohort from aHawaiian birthdefects registry

Self-report inmedical recordor positive urinetoxicology screenat delivery

Reported use:yes/noTHC in maternalurine at time ofdelivery (orderedclinically)

None n ¼ 109 total cases ofgastroschisis, n ¼ 3 casesof gastroschisis inmarijuana-exposedRate ratio of marijuana userscompared with women withother live births, 23.11; 95%CI, 4.69e69.34

Low prevalence ofmarijuana use (0.3%)indicates incompleteascertainment ofexposureNo adjustment forpossible confoundersNo data on trimesterof exposureMarijuana use notwell quantified

van Gelder et al, 2009b42

(n ¼ 10,241 cases withanomalies and 4967controls)

610 (4) Retrospectivecohort from amultistate birthdefects registry

Self-report bystructuredinterview6 wks to 24 moafter delivery

Reported use:yes/no from1 month beforepregnancy toend of pregnancy

Standard demoincluding maternalage at delivery,EtOH, tobacco, folicacid use, maternaldiabetes

n ¼ 485 total cases ofgastroschisis, n ¼ 189cases of gastroschisis inmarijuana-exposedNo association withgastroschisis (OR, 1.3; 95%CI, 0.9e1.8)

Possible recall bias,women interviewed 6wks to 24 mo afterdeliveryNo data on trimesterof exposureMarijuana use notwell quantified


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TABLE 4Summary of marijuana and congenital anomalies studies (continued)


Marijuana-exposedwomen, n (%)

Study designand setting Data source

Marijuanameasure


Findings (adjustedORs with 95% CIsreported whenavailable)


Ventricular septal defect

Williams et al, 200443

(n ¼ 122 cases with aVSD and 3029 controls)

253 (8) Retrospectivecohort fromAtlanta BirthDefectsCase-ControlStudy

Self-report bystructuredtelephoneinterviewpostpartum

Reported use: �2 d/wk, �3 d/wk from3 months beforepregnancy to endof first trimester

Cases matched tocontrols by birthyear, race, birthperiod, and hospitalof birthAdjusted for maternalage, multivitaminuse, maternaldiabetes

n ¼ 122 total casesof VSD, n ¼ 20 casesof VSD in marijuanaexposedMarijuana use associatedwith VSD (adjusted OR,1.90; 95% CI, 1.29e1.81)

Possible recall bias,women interviewed afterdeliveryIncompleteascertainment ofconfounding factorsMarijuana use notwell quantified

van Gelder et al, 200942



Self-report bystructuredinterview 6 wksto 24 moafter delivery

Reported use:yes/no from 1 mobefore pregnancyto end ofpregnancy

Standard demoincluding maternalage at delivery, EtOH,tobacco, folic aciduse, maternaldiabetes

n ¼ 927 total casesof perimembranous VSD,n ¼ 34 casesof perimembranous VSDin marijuana-exposedNo association with VSD(OR, 0.9; 95%CI, 0.6e1.4)

Possible recall bias,women interviewed6 wks to 24 mo afterdeliveryNo data on trimesterof exposureMarijuana use notwell quantified

Anencephaly

van Gelder et al, 200942



Self-report bystructuredinterview6 wks to 24 moafter delivery

Reported use:yes/no from1 month beforepregnancy toend ofpregnancy

Standard demoincluding maternalage at delivery, EtOH,tobacco, folic aciduse, maternaldiabetes

n ¼ 244 total cases ofanencephaly, n ¼ 12 casesof anencephaly in marijuanaexposedMarijuana use associatedonly with anencephaly in asubanalysis restricted tofirst month after conceptionexposure (OR, 2.5; 95%CI, 1.3e4.9)

Possible recall bias,women interviewed6 wks to 24 mo afterdeliveryNo data on trimesterof exposureMarijuana use notwell quantified

CI, confidence interval; EtOH, alcohol use; Medical hx, medical history; OB hx, obstetrical history; OR, odds ratio; SES, socioeconomic status; Standard demo, some measure of standard demographics including maternal age, race, body mass index; THC, delta-9-tetrahydrocannabinol; VSD, ventricular septal defect.

a Rates of other birth defects that were higher in women with isolated (no other drug use) marijuana use in study by Forrester et al41 (2007) were encephalocele, hydrocephaly, microcephaly, anotia/microtia, tetralogy of Fallot, atrial septal defect, pulmonary valveatresia/stenosis, hypoplastic left heart syndrome, cleft lip and palate, pyloric stenosis, anal/rectal/large intestinal atresia/stenosis, obstructive genitourinary defect, polydactyly, syndactyly, and reduction deformity of upper limbs. These findings are not furtherdescribed, given the limitations in the methodology of this study with no correction for possible confounders; b No association was found between marijuana and several other birth defects in the study by van Gelder et al42 (2009) including spina bifida, anotia/microtia, d-transposition of the great arteries, tetralogy of Fallot, hypoplastic left heart syndrome, coarctation of the aorta, pulmonary valve stenosis, atrial septal defect, cleft lip and palate, esophageal atresia, anorectal atresia, hypospadias, transverse limbdeficiency, craniosynostosis, and diaphragmatic hernia.


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TABLE 5Recommendations for clinicians regarding marijuana use in pregnancyRecommendations

Screen all women verbally for marijuana use at intake to obstetrical careConsider rescreen later in pregnancy

Consider urine toxicology screening in high-risk patientsRecommend avoiding marijuana in pregnancyMarijuana crosses the placentaCounsel women regarding uncertainty of effects on perinatal outcomesPossible increased risk of stillbirth

Possible increased risk of preterm birth (mixed data)Counsel women regarding uncertainty of effects on offspringPossible adverse effects on neurodevelopment

Possible increased risk of fetal growth restriction (mixed data)

No established association with specific congenital anomaliesRefer women who use marijuana and desire cessation to appropriate resourcesLocal substance-use programsDo not otherwise modify clinical careGrowth ultrasounds not indicated outside study protocols

Screening for preterm birth with cervical length not indicated

Antenatal surveillance not indicatedRecommend avoiding marijuana while lactatingMarijuana is passed to the neonate in breast milk

Possible adverse effects on early neurodevelopment

Provide counseling, but do not withdraw lactation support

Recommendations in the Table above reflect the opinions of the authors after a thorough review of the existing literature onmarijuana in pregnancy and lactation.



nonexposed infants of demographicallymatched mothers.49 Exposure wasconfirmed by maternal hair samples andneonatal meconium testing. Thoseexposed to marijuana had significantlydifferent arousal, regulation, and excit-ability on the Neonatal Intensive CareUnit Network Neurobehavioral Scale.

There are 2 large cohorts with bothshort- and long-term follow-up ofchildren exposed to marijuana in utero.The Ottawa Prenatal Prospective Studylooked at the effects of prenatal mari-juana and tobacco use on 180 offspringof primarily middle class, white, low-risk patients in Ottawa, Canada, atvarious developmental ages.50 Youngerthan age 4 years, there were no differ-ences in behavior problems, intellect,visual perception, language, or sus-tained attention and memory tasks be-tween children born to mothers whoused marijuana and those who didnot. However, after the age of 4 years,there were differences in behavioralproblems and poorer performance onvisual perception tasks as well as lan-guage comprehension and sustainedattention and memory difficulties inexposed children.50 By the age of 9-12years, there was no difference betweenexposed and unexposed children inglobal intelligence quotient scores orperformance on visual tasks and im-pulse control.51

Although the Ottawa Prenatal Pro-spective Study provides much-neededlong-term follow-up of exposed chil-dren, it has limitations. It does notadequately correct for environmentalfactors, does not clearly report differ-ences based on the quantity of marijuanaused, and is a relatively homogenouspopulation.

The other large cohort with long-termfollow-up is the Maternal Health Prac-tices and Child Development Project(MHPCD) from Pittsburgh, PA, whichconsists of mostly high-risk, low-incomeminority women and their children.52

Whereas there were no differences inintelligence testing at 3 years of age,52

maternal use of 1 or more joints perday during the first trimester was asso-ciated with decreased verbal reasoningby the age of 6 years.53


The MHPCD cohort was examinedagain at age 10 years (n ¼ 636). Thosechildren exposed during the first andthird trimesters demonstrated decreasedattention and more hyperactivity andimpulsivity.54 Academic performance inreading and spelling and by teacherreport was worse in those exposed to atleast 1 joint per day during pregnancy.55

In the last assessment of the MHPCDcohort at the age of 14 years (n ¼ 524),maternal use was associated with lowerscores in reading, math, and spelling,most notably in those exposed to heavyuse in the first trimester.56 In addition,there was an earlier age of onset of sub-stance use and greater duration of usethan their matched counterparts, evenafter adjustment for home environmentand parental substance use.57

Although the human research inneonatal and childhood developmentfollowing marijuana exposure is flawedby factors including the concurrentuse of other substances, variability inexposure dosing and frequency, othergenetic or environmental factors, and a


reliance on self-reported data, there is aconcerning pattern of altered neuro-development with early, heavy maternaluse of marijuana.

Breast-feedingCannabinoids consumed by lactatingmothers reach the newborn duringbreast-feeding.58 The amount that rea-ches the infant is estimated at 0.8% ofthe mother’s exposure.59 There is someevidence that marijuana use inhibitsmilk production by inhibiting prolactinsecretion.60

Astley and Little61 attempted to deter-mine the effects ofmarijuana use on infantdevelopment at 1 year. Infants exposed tomarijuana during lactation scored poorlyon the Psychomotor Developmental In-dex compared with those not exposed.However, this result could not be sepa-rated from the effect of marijuana useduring pregnancy.61 Eighty-four percentof users during pregnancy continued useduring lactation.61

The American Academy of Pediatrics’policy statement on “Breastfeeding and


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the Use of Human Milk” states thatbreast-feeding is contraindicated inwomen using illicit drugs.62 The state-ment does not address whether hospitalsshould withdraw lactation support inthe form of facilitation of breast-feedingby nursing and lactation consultants. Inour opinion, given the paucity of dataregarding ongoing exposure to mari-juana through breast milk, and multipleknown benefits of breast-feeding, lacta-tion support should not be withdrawn.However, women should clearly beeducated regarding the potential adverseeffects of ongoing marijuana exposurethrough breast milk and encouraged tostop using marijuana while lactating.

Future researchDespite a large volume of literature onthe topic of marijuana in pregnancy,there is still a need for high-quality,contemporary, prospective data to bet-ter understand the effects of marijuanause in pregnancy and lactation.

We have identified the followingresearch gaps as areas of focus for futurestudies: (1) determining whether there isan association between marijuana useand congenital anomalies, spontaneouspreterm birth, pregnancy loss and still-birth, or poor fetal growth by serial ul-trasound assessments; (2) confirmingthe long-term neurobehavioral conse-quences of marijuana exposure withlongitudinal follow-up; (3) establishingwhether there are adverse effects ofbreast-feeding in the setting of ongoingmarijuana use; (4) characterizing thechanges in the prevalence of use duringpregnancy in states with legalized mari-juana for medical and recreational use;(5) understanding women’s attitudesand beliefs regarding marijuana inpregnancy in the setting of increasinglegalization; and (6) understanding theimpact of different modes of consump-tion on outcomes with increased use ofedible forms of marijuana that containhigh concentrations of THC.

While performing any study onmarijuana, it will be important to collectparticipant’s socioeconomic status, me-dical history, obstetrical history, use ofother drugs, and alcohol and tobacco usein a detailed, methodical manner. In



addition, studies will need to quantifythe timing and the amount of marijuanaingested and corroborate self-reportwith biological specimens.Ultimately high-quality data will

enable obstetricians to appropriatelycounsel women regarding marijuana usein pregnancy. If adverse effects areconfirmed, intervention and educationprograms can be developed to minimizemorbidity to mothers and their babies.

SummarySummary recommendations for thepracticing clinician are listed in Table 5.These recommendations are made aftera thorough review of the existing litera-ture but are based on studies of varyingmethodological quality with mixed re-sults and reflect the opinions of the au-thors after completing this extensivereview. Until further data are available,we should continue to discouragewomen from using recreational drugs,including marijuana, during pregnancyand lactation, given the uncertain short-and long-term outcomes. -

ACKNOWLEDGMENT

We appreciate the work of Lilian Hoffecker, aresearch librarian at the University of ColoradoHealth Sciences Library, in assisting with theextensive literature search needed to completethis review.

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