Objective
The aim of this study was to systematically review the relationship between amphetamine exposure in pregnancy and birth outcomes.
Study Design
Electronic databases were searched to identify relevant studies. Data from included studies were extracted by 2 reviewers. Summary odds ratio (OR) and confidence intervals (CIs) were calculated using the random effects model.
Results
Ten studies were included. Significant increases in unadjusted risks of preterm birth (OR, 4.11; 95% CI, 3.05–5.55), low birthweight (OR, 3.97; 95% CI, 2.45–6.43), and small for gestational age (OR, 5.79; 95% CI, 1.39–24.06) were identified among women exposed to amphetamines in pregnancy. The mean birthweight was significantly lower among amphetamine-exposed pregnancies (mean difference, −279 g; 95% CI, −485 to −74 g). Two studies provided adjusted estimates on different outcomes, and their results were consistent with the findings from the unadjusted data.
Conclusion
Amphetamine exposure in pregnancy is associated with adverse birth outcomes and should be identified by physicians providing antenatal care.
Low birthweight (LBW) and preterm birth (PTB) are associated with short- and long-term morbidities. Lifestyle factors, such as illicit substance exposure, have been implicated in restricting fetal growth and causing the onset of PTB. Amphetamines are addictive stimulants, whose use is increasing globally in the general population and among pregnant women. A survey of 4500 youths in Thailand reported that 1 in 4 individuals admitted to previous methamphetamine use. In the United States, it has been estimated that 5% of all pregnant women have used methamphetamines. Among pregnant women, amphetamine use accounted for 8% of hospital admissions for substance use in 1994. This rate increased to 24% of hospital admissions related to substance use in 2006.
The reported impact of amphetamine exposure on birth outcomes has been variable. In sheep, methamphetamine use has been found to decrease uterine blood flow, increase uterine vascular resistance, and increase fetal blood pressure, all in a dose-related fashion. These effects have been postulated to impact the growth of the fetus, as well as the development of the placenta, and thus lead to adverse perinatal outcomes.
The objective of this study was to systematically review the impact of amphetamine use during pregnancy on PTB, LBW, and small for gestational age (SGA) births.
Materials and Methods
Study question
Are women who are exposed to amphetamines during pregnancy at increased risk of adverse birth outcomes compared with unexposed women?
We followed the Metaanalyses of Observational Studies in Epidemiologic Studies (MOOSE) criteria.
Ethics: the data were extracted from published manuscripts and thus, no ethics board approval was necessary.
Criteria for considering studies for this review: observational cohort studies with matched, unmatched, or historic controls; longitudinal studies; and case-control studies that assessed the association of maternal amphetamine exposure and the outcomes of LBW, PTB, and SGA births were included. Included studies clearly described the method of ascertainment of the maternal exposure to amphetamines and assessed the outcomes of interest. All data were obtained from full publications; no abstracts were included, and no primary authors were contacted. Data on combined substance exposure, where specific details regarding amphetamine exposure could not be obtained, were excluded from the analysis.
Reports of data from national or local vital statistics not published as peer-reviewed articles were excluded.
Types of participants
Women who had live births were included (stillbirths were excluded, as often their maturity and weight are not accurately recorded).
Assessment of exposure
Details regarding the mother’s amphetamine exposure were elicited during history or by self-administered questionnaires in most instances; however, objective ascertainment data were also collected when available. Further details on maternal characteristics were ascertained from medical records, hospital records, administrative databases, national databases, or vital statistics in most studies, and these data were included.
Types of outcome measures
Studies reporting on data on any of the following outcomes were included. Outcomes of interest included (1) LBW defined as birthweight <2.5 kg; (2) PTB defined as gestational age <37 weeks; (3) SGA defined as birthweight below 10th percentile for gestational age; (4) birthweight in grams; and (5) gestational age at birth in weeks.
Literature search
The published literature from 1950 until August 2010 was searched using Medline, EMBASE, and CINAHL databases. The terms “pregnancy,” “amphetamine,” and “amphetamine-related disorders” were searched as MESH keywords. The resultant abstracts were then reviewed, and relevant studies were included for detailed evaluation by 2 authors (N.L. and K.M.). Studies published in any language were included. Reviews were excluded, but their reference lists were hand searched, as were the reference lists of all relevant articles.
Methods of the review
Data extraction: data from eligible studies were extracted without modification onto custom-made data collection forms by 2 authors (N.L. and K.M.). Discrepancies were resolved by consensus and by involvement of a third author (P.S.). Information on confounders in the form of adjusted risk estimates (adjusted odds ratios [ORs] or adjusted risk ratios) were collected when available. Not all studies reported on all outcomes.
Assessment of quality of included studies: two authors (N.L. and K.M.) independently assessed the methodologic quality of studies assessed using a predefined checklist developed as part of comprehensive systematic reviews on this topic ( Table 1 ). Discrepancies were resolved by consensus and the involvement of a third author (P.S.).
| Author | Year of study | Type of study | Setting | Population | Exposure assessment | Outcomes assessed | Confounders adjusted for |
|---|---|---|---|---|---|---|---|
| Little et al | 1987 | Cohort study with unmatched concurrent controls | Tertiary hospital in Dallas, TX | All women | Self-report | BW, GA | None |
| Gillogley et al | 1987-1988 | Cohort study with matched concurrent controls | Tertiary obstetric centre in Sacramento, CA | All women | Urine toxicology screen | LBW, PTB | None |
| Smith et al | 1997-1999 | Cohort study with matched concurrent controls | Tertiary hospital in Los Angeles, CA | All women | Urine test or self-report | GA, BW, SGA | None |
| Chomchai et al | 2001 | Cohort with matched concurrent controls | Teaching hospital in Bangkok, Thailand | All pregnant women admitting to methamphetamine use | Urine screening by FEIA of infants | BW, GA | None |
| Ludlow et al | 1997-2001 | Cohort study with unmatched concurrent controls | Tertiary hospital in Perth, Australia | Exposed women | Self-report | LBW, PTB | None |
| Smith et al | 2002-2003 | Cohort study with unmatched concurrent controls | Clinical sites in Los Angeles, CA; Des Moines, IA; Tulsa, OK; Honolulu, HI | All women | Maternal self-report and meconium testing | GA, PTB, SGA | Socioeconomic status; income; single parenthood; prenatal care; alcohol, tobacco, and marijuana use |
| Phupong and Darojn | 2002-2003 | Cohort study, retrospective, with matched concurrent controls | Tertiary hospital in Bangkok, Thailand | Pregnant women exposed to amphetamine | Maternal self-report | GA, BW, SGA | None |
| Cox et al | 1998-2004 | Cohort with unmatched concurrent controls | Community hospitals in the United States | National database with code for amphetamine use | PTB | Age; primary payor; hospital location; geographic region; diagnosis of alcohol, opioid, cannabis, or tobacco abuse | |
| Nguyen et al | 2002-2003 | Cohort study with unmatched concurrent controls | Clinical sites in Los Angeles, CA; Des Moines, IA; Tulsa, OK; Honolulu, HI | All women | Maternal self-report and meconium testing | GA, PTB, SGA | Socioeconomic status; income; single parenthood; prenatal care; alcohol, tobacco, and marijuana use |
| Good et al | 2000-2006 | Retrospective cohort with unmatched controls | Urban medical center in Phoenix, AZ | All women | Maternal self-report and urine testing | PTB | None |
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