Methamphetamine Use During PregnancyMaternal and Neonatal Implications

Meadow M. Good, DO, Ido Solt, MD, Joann G. Acuna, MD, Siegfried Rotmensch, MD,and Matthew J. Kim, MD

OBJECTIVE: To report the demographic characteristicsand clinical morbidity of methamphetamine-exposedpregnancies compared with control patients in a tertiarycare, urban, academic medical center.

METHODS: A single-site chart review from 2000 to 2006was conducted. International Classification of Diseases,9th Revision code 648.3x was used to identify potentialstudy participants. Specific inclusion criteria requiredeither a positive urine drug screen for methamphetamineuse or by patient statement of methamphetamine useduring pregnancy. Data from 276 identified patients werethen compared with the 34,055 in the general obstetricpopulation during the same period for various demo-graphic factors and perinatal outcomes.

RESULTS: Two hundred seventy-six patients responsiblefor 273 live births were identified between 2000 and2006. Factors that were significantly associated withmethamphetamine use were age younger than 20 years(9% methamphetamine compared with 16% control pa-tients), non-Hispanic white ethnicity (55% comparedwith 71%), married (12% compared with 46%), pretermdelivery (52% compared with 17%), low Apgar scores (6%compared with 1–2%), cesarean delivery (29% comparedwith 23%), and neonatal mortality (4% compared with1%). Additionally, the maternal demographic character-istics suggested that these women were more likely to beunemployed, use other abusive substances, and havehigher rates of domestic violence and adoption whencompared with the control population.

CONCLUSION: Methamphetamine use in pregnancy iscomplicated by more morbid maternal and neonataloutcomes when compared with the general obstetric

population. Because the patients in this study were in avariety of ways demographically distinct, attempts toidentify these patients early and intervene in an effort toimprove pregnancy-related outcomes appears possibleand warranted.(Obstet Gynecol 2010;116:330–4)

LEVEL OF EVIDENCE: II

Methamphetamine dependence is an escalatingproblem across the United States. Methamphet-

amine (N-methyl-1-phenyl-propan-2-amine) is the onlyillegal drug that can be easily made from legally ob-tained ingredients, in particular over-the-counter coldmedications or decongestants. Available in crystal formor as a white, odorless powder, methamphetamine canbe swallowed, smoked, injected, or inhaled. It has highbioavailability: 62.7% oral, 79% nasal, 90.3% smoked,99% rectally, and 100% intravenously, with a half life of9–15 hours. A powerful stimulant, methamphetamineincreases the release of catecholamines and dopamineand also inhibits the degradation of neurotransmitters.1,2

The drug can be detected unchanged in a person’surine or blood for up to 3 days. A recent report suggestsmany users are addicted after a single exposure as aresult of its long euphoria of up to 24 hours, ease ofproduction, and relatively low cost.3 The Center forSubstance Abuse Research’s Infant Development, Envi-ronment, and Lifestyle (IDEAL) study reported that5.2% of women in particularly high methamphetamineprevalent regions of the United States used metham-phetamine at some point during their pregnancy.4 De-spite the increasing use of the drug, knowledge of actualeffects in pregnancy is limited.5,6

A remarkable increase in the incidence of meth-amphetamine-exposed pregnancies and related com-plications have been anecdotally reported. However,there is a paucity of reports specific to methamphet-amine and human pregnancy. This study was thusundertaken to validate the hypothesis that metham-

From the Division of Maternal Fetal Medicine, Department of Obstetrics/Gynecology, Cedars-Sinai Medical Center, Los Angeles, California.

Corresponding author: Ido Solt, MD, Division of Maternal Fetal Medicine,Department of Obstetrics and Gynecology, 8635 West 3rd Street, Suite 160W,Los Angeles, CA 90048; e-mail: Solti@cshs.org; ido.solt@gmail.com.

Financial DisclosureThe authors did not report any potential conflicts of interest.

© 2010 by The American College of Obstetricians and Gynecologists. Publishedby Lippincott Williams & Wilkins.ISSN: 0029-7844/10

330 VOL. 116, NO. 2, PART 1, AUGUST 2010 OBSTETRICS & GYNECOLOGY

phetamine exposed pregnancies have greater perina-tal morbidity.

MATERIALS AND METHODSA single-site review of medical records of hospitalizedpatients was conducted for the period from January2000 through March 2006. St. Joseph’s Hospital andMedical Center is a 697-bed tertiary care, urban, aca-demic, not-for-profit medical center. This study wasapproved by the Institutional Review Board for HumanResearch of St. Joseph’s Hospital and Medical Center(#06OB039, April 20, 2006) in Phoenix, AZ.

Administrative data were used for patient identi-fication. International Classification of Diseases, 9thRevision code 648.3x (drug dependence complicatingpregnancy, childbirth, or the puerperium) was used toscreen all patient medical records for detailed review.Analysis of records identified on initial screening wasthen performed to select methamphetamine users.

The specific inclusion criteria required either apositive urine drug screen for methamphetamine orby patient statement of methamphetamine use duringpregnancy. In this institution, all patients are routinelyasked if illicit drugs have been used. A urine drugscreen was also performed in patients with apparentsubstance abuse or in certain presenting circum-stances at admission in the hospital chemistry labora-tory (Triage Drugs of Abuse Panel; Biosite Inc., SanDiego, CA). These records were then analyzed forperinatal complications, and outcomes, along withneonatal outcomes.

The maternal charts were evaluated for the fol-lowing demographic data: maternal age, ethnicity,employment status, education, marital status, domes-tic violence, smoking, and prenatal care. The neonatalcharts were evaluated for the following: gestationalage, Apgar score, site and mode of delivery, disposi-tion of the neonate, and neonatal mortality.

These data were compared with a general controlpopulation of women presenting for obstetric care tothis institution during this same period. Statisticalanalysis was performed using the �2 test. Statisticalsignificance was defined as P�.05.

RESULTSTwo hundred seventy-six patients responsible for 273live births were identified as methamphetamine usersand pregnant. Although control comparison data werenot available for all demographic and outcomeparameters, as a result of sparse data recording inroutine uncomplicated births, the following resultsare noteworthy regarding the methamphetamine-ex-posed patients.

The study institution experienced a remarkableincrease in the number of patients using methamphet-amine in pregnancy: 22 patients in 2001, 43 in 2004,and 77 patients in 2005.

Only 19 of 276 (7%) reported being employed,and 79 of 141 (56%) had an 11th grade education orless. Furthermore, there was an unusual preponder-ance of non-Hispanic white (152 of 276 [55%]) pa-tients in the methamphetamine population comparedwith the general hospital population demographic.Distribution of ethnicity was as follows: 35% Hispan-ics, 5% African Americans, 3% Native Americans,and 2% other or unknown.

These findings were inconsistent with our anec-dotal experience among patients presenting for careat this institution, which serves a predominantly em-ployed Hispanic married community. Furthermore,the majority, 213 of 275 (78%), were active tobaccosmokers, 39 of 275 (14%) consumed alcohol on aregular basis, 168 of 275 (61%) tested positive for illicitsubstances at the time of presentation to the hospital,and 66 of 275 (24%) tested positive for multiple illicitsubstances (methamphetamine and tetrahydrocan-nabinol [n�47], opiates [n�14], cocaine [n�13],phencyclidine [n�2], and more than one other illicitdrug [n�11]).

These patients had high-risk pregnancies for mul-tiple reasons: 133 of 265 (50%) had preterm birth (52had birth at 35–36 weeks, 44 had birth at 33–34weeks, and 37 had birth at 20–32 weeks of gestation).In 11 cases, gestational age at delivery could not beverified. Most of the preterm deliveries were idio-pathic. Thirty-two of 265 (12%) had intrauterinegrowth restriction,7 48 of 274 (17%) had a hyperten-sive complication not related to diagnostically classicpreeclampsia, 25 of 272 (9%) had placental abruption,and 25 of 275 (9%) were hospital-to-hospital transport.The majority of patients delivered through spontane-ous vaginal delivery (195 of 276 [71%]). Alarmingly,domestic violence during pregnancy was reported by51 of 225 (23%).

Table 1 illustrates statistically significant differencesin maternal demographics between patients using meth-amphetamine and a nonmethamphetamine-exposedcontrol population (n�34,055). Clearly the metham-phetamine group represented a cohort of women whowere generally older, did not avail themselves of theusual prenatal care, and were substantially less likely tobe legally married.

Statistically significant differences between pa-tients using methamphetamine and a nonmetham-phetamine-exposed control population with regard toperinatal outcomes is shown in Table 2. Although

VOL. 116, NO. 2, PART 1, AUGUST 2010 Good et al Methamphetamine Dependence and Pregnancy 331

these pregnancy outcomes clearly suggest more pre-term birth in patients using methamphetamine withwhat is likely associated lower initial Apgar scoring,the incidence of neonatal mortality is high.

Additionally, the following outcomes were alsonoted: 15 of 276 (6%) had an unattended out-of-hospital delivery (car, toilet, home, ambulance) and87 of 215 (40%) of these pregnancies ended in initialmother and infant separation (adoption 45%, ChildProtective Services or foster care 45%, primary caregiver other than mother 10%), which included plannedadoptions (23 of 215 [11%]). More concerning clinically,there is a suggestion of a need for much higher acuitycare in patients with methamphetamine use.

Finally, the record review strongly suggested sub-stantially increased demands on nursing staff (neonatalabstinence protocols, collection of specimens for drugsof dependance, management of withdrawal symptoms,lack of parental involvement in care), but this was asubjective observation and difficult to quantify in areliable manner. Also of note were the anomalies foundin this neonatal population, which included anenceph-aly, ambiguous genitalia, cleft lip, and diaphragmatic

hernia, although not statistically significant as a result oflow overall incidence.

DISCUSSIONThe study institution has experienced a remarkableincrease in the number of patients using methamphet-amine in pregnancy. A recent U.S. study reported thatin 1994, methamphetamine accounted for 8% ofadmitted pregnant women with substance abuse, ris-ing to 24% by 2006. The majority of methamphet-amine admissions occurred in the West (73%) amongwhite (64%) unemployed (88%) women.8 Similaryear-to-year increases have been noted internation-ally, particularly in Pacific rim countries such as NewZealand and Thailand.9,10 In a study of methamphet-amine use patterns during pregnancy, among 191users, the prevalence of methamphetamine use de-creased over the three trimesters of pregnancy (84.3%compared with 56.0% compared with 42.4%), anddecreased frequency was observed among users fromthe first trimester to the third (3.1 compared with 2.4compared with 1.5 days per week).11

This patient population has many characteristicsthat led to a high-risk pregnancy, including domesticviolence, substance abuse, and poor prenatal care,which may be directly linked to the observed rates ofhypertension, placental abruption, and maternal andneonatal intensive care unit admission.

Methamphetamine use is associated with a risk ofacute death, often as a result of hypertensive eventssuch as cerebrovascular accident.12 Studies have alsoshown physical effects in rats, including histologicallyapparent brain alterations and evidence of oxidativeDNA damage.13 Likewise, retrospective human stud-ies have shown methamphetamine is negatively associ-ated with gestational age, birth weight, length, andoccipitofrontal circumference.14 Other investigatorshave reported on the very real impact of methamphet-amine on maternal and neonatal mortality as well.Catanzarite and Stein15 submitted a case report on twomaternal deaths in their institution resulting from car-diac decompensation perhaps attributable to metham-phetamine use. Similarly, Stewart and Meeker16 de-scribed eight cases of fetal or neonatal death attributedto methamphetamine. However, with the exception ofthis study, a more generalized report of methamphet-amine use in pregnancy and its attendant complicationshas not been published.

Perinatal complications were not solely limited toclinical outcomes but also involved an apparent dra-matic breakdown of expected mother–infant bondingas demonstrated by the exceedingly high foster careand adoption rate. Animal reports, mostly focused on

Table 2. Perinatal Outcomes

PerinatalCharacteristics

MethamphetamineUsers

(n�273)

ControlPatients

(n�34,055) P*

Preterm delivery 139 (52) 5,627 (17) �.0011-min Apgar

score less than 416 (6) 665 (2) �.001

5-min Apgarscore less than 7

16 (6) 328 (1) �.001

Cesarean delivery 79 (29) 7,730 (23) �.02Neonatal mortality 11 (4) 325 (1) �.001Maternal obstetric �

intensive careunit admissions

6 (2) 95 (0.3) �.001

Data are n (%) unless otherwise specified.* P from �2 test.

Table 1. Maternal Demographics

MethamphetamineUsers

(n�276)

ControlPatients

(n�34,055) P*

Age younger than20 y

25 (9) 5,449 (16) �.01

Obstetric visitsfewer than 5

190 (69) 3,324 (10) �.001

Hispanic ethnicity 152 (55) 24,179 (71) �.001Married 34 (12) 15,686 (46) �.001

Data are n (%) unless otherwise specified.* P from �2 test.

332 Good et al Methamphetamine Dependence and Pregnancy OBSTETRICS & GYNECOLOGY

rat behavior, have demonstrated similar striking alter-ations in maternal interest in pup well-being.17,18 Infact, news reports in Phoenix, AZ, note that two thirdsof child abuse and neglect cases are related to meth-amphetamine in some way.19 Although a substantialportion of the mother–infant separations in our studywere court-ordered events, the high planned adoptionrate suggests a marked alteration in typical bonding.

Other investigators have noted that methamphet-amine not only freely crosses the placenta,20,21 but thatdirect methamphetamine effects or the presence ofmethamphetamine itself is measurable in animal fetalorgans, including the heart and brain.22–25 Similarfindings in human studies have increased the level ofurgency for a better understanding of methamphet-amine and its effects, particularly in children andpregnancy.26,27 In 1988, Little et al28 studied 52 meth-amphetamine users during pregnancy. They reportedthat neonatal body weight, length, and head circum-ference were significantly decreased compared withcontrol newborns. Increasing evidence indicates thatprenatal exposure to methamphetamine results insevere morphological changes in the brain with asso-ciated cognitive deficits.25 In fact, half of the newbornswhose mothers used methamphetamine during preg-nancy experienced withdrawal syndrome.

In a recent case–control study of a gastroschisiscluster in Reno, NV, gastroschisis was found to beassociated with the use of methamphetamine with anodds ratio of 7.15 and a 95% confidence interval of1.35–37.99.29 Prenatal methamphetamine exposureinfluences the development of the verbal memorysystem above the effects of prenatal alcohol expo-sure.26 Thus, there has been recent interest in methodsto track the long-term outcomes in these neonates.Although studies have not as yet evaluated suchlong-term outcomes, reports would suggest an in-crease in behavioral disorders and difficulty achievingdevelopmental milestones. Furthermore, metham-phetamine-exposed neonates tax the hospital staff andburden the state foster care system. This increase inthe cost of care, although not quantified in our data, isdirectly related to the high level of caregiver surveil-lance required by these newborns from birth untildischarge and is not an insignificant problem.30,31

The data presented in this study have severallimitations. Our screening method for methamphet-amine users in pregnancy relied on patient admit-tance to using the drug or a positive urine toxicologyscreen. The toxicology screen is not routine, per-formed only after poorly described and documentedcircumstances as defined by individual caregivers.This informal screening process undoubtedly results

in missed patients who are using methamphetamineor other substances. In addition, the possibility of afalse-positive urine screen as a result of labetalol,ephedra, or other substances cannot be ruled out withabsolute certainty.32 Also, with almost one fourth ofmethamphetamine users in our population usingother illicit substances and most smoking tobacco, it isdifficult to correlate the patients’ acute medical issuesand outcomes with only the methamphetamine use.Finally, this study includes a single urban hospital ina region with widespread methamphetamine abuse;thus, it may not be valid in rural areas or other regionswith a difference in methamphetamine prevalence.

An interesting aspect of our data review was theunusual demographic characteristics of the metham-phetamine-using cohort. They were fairly distinctfrom the typical population in the study hospital,representing as noted an older, smoking, less edu-cated, unemployed, white non-Hispanic woman witha probable history of domestic violence. This patternof factors was so distinct that it may allow screening ina more directed manner those patients who may bemethamphetamine users. Validation of similar patientbackground demographics in other regions would beof great interest. In conclusion, methamphetamineuse in pregnancy is complicated by more morbidmaternal and neonatal outcomes when comparedwith the general obstetric population. The incidenceof methamphetamine use is rising; attempts to iden-tify these patients early and intervene in an effort toimprove pregnancy-related outcomes are warranted.

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