Elsevier

Reproductive Toxicology

Volume 15, Issue 4, July–August 2001, Pages 341-369
Reproductive Toxicology

Fetal effects of cocaine: an updated meta-analysis

https://doi.org/10.1016/S0890-6238(01)00136-8Get rights and content

Abstract

Background: A very large number of women in the reproductive age group consume cocaine, leading to grave concerns regarding the long term health of millions of children after in utero exposure. The results of controlled studies have been contradictory, leading to confusion, and, possible, misinformation and misperception of teratogenic risk.

Objective: To systematically review available data on pregnancy outcome when the mother consumed cocaine.

Methods: A meta-analysis of all epidemiologic studies based on a priori criteria was conducted. Comparisons of adverse events in subgroups of exposed vs. unexposed children were performed. Analyses were based on several exposure groups: mainly cocaine, cocaine plus polydrug, polydrug but no cocaine, and drug free.

Results: Thirty three studies met our inclusion criteria. For all end points of interest (rates of major malformations, low birth weight, prematurity, placental abruption, premature rupture of membrane [PROM], and mean birth weight, length and head circumference), cocaine-exposed infants had higher risks than children of women not exposed to any drug. However, most of these adverse effects were nullified when cocaine exposed children were compared to children exposed to polydrug but no cocaine. Only the risk of placental abruption and premature rupture of membranes were statistically associated with cocaine use itself.

Conclusions: Many of the perinatal adverse effects commonly attributed to cocaine may be caused by the multiple confounders that can occur in a cocaine using mother. Only the risk for placental abruption and PROM could be statistically related to cocaine. For other adverse effects, additional studies will be needed to ensure adequate statistical power.

Introduction

The high prevalence of cocaine use has become a major health concern during pregnancy. Cocaine crosses the human placenta, with varying proportions absorbed by the placenta, suggesting that the placenta may offer a degree of protection to some fetuses after bolus administration [1]. Cocaine is a CNS stimulant with effects thought to be due to its sympathomimetic-driven fetal, uterine, or maternal vasoconstriction and hypertension leading to infarcts or hemorrhages at any time during gestation and in any structure. This feature may explain the variability of clinical effects attributed to cocaine use. A typical well-defined “fetal cocaine syndrome” has not been identified [2]; however, exposure to cocaine during pregnancy has been associated with shorter gestation, premature delivery, abruptio placenta, and other maternal and neonatal adverse effects. In the past, congenital malformations of almost every system have been reported leading many clinicians to believe that the drug is teratogenic [3]. Reports of fetal cocaine effects have been controversial and it has been difficult to elucidate these effects, because interpretation of the results is hampered by the fact that cocaine use is commonly accompanied by confounding factors such as concomitant use of cigarettes and other recreational drugs, including heroin, cannabis, methadone, and others, all of which may affect pregnancy outcome by themselves.

Our original systematic review and meta-analysis in 1991 [4] suggested that cocaine exposure during pregnancy is not a major risk for malformation (except for the genitourinary tract). When cocaine users were compared to women not consuming any drugs of abuse, a variety of risks emerged. Yet when we compared pregnancy and neonatal outcomes in children of cocaine consumers with polydrug consumers, the increased risk for most of the adverse outcomes was nullified. A major issue at that stage was the relatively small number of studies for each adverse end point. Since 1989 (the last year included in our previous meta-analysis), however, scores of studies on cocaine exposure during pregnancy have been published. Hence, the present meta-analysis has allowed us to separate the exposure data into several comparisons:

  • 1.

    between all combinations of exposures that involve cocaine use during pregnancy (cocaine alone, polydrug including cocaine, polydrug not including cocaine);

  • 2.

    between the different methodologies used to determine exposure (urine analysis, maternal interview, chart review).

The aim of this updated meta-analysis was to arrive at an overall quantitative estimate of the effect of cocaine use on pregnancy outcome and potential pregnancy complications, with a substantially increased power.

Section snippets

Data sources

The medical literature published between January 1989 and December 1997 was searched for papers dealing with the outcome of pregnancy following gestational cocaine exposure. The literature search was performed in the MEDLINE and EMBASE bibliographic databases. A search strategy using a combination of “pregnancy ” or “abnormalities drug induced ” and “cocaine ” keywords (MeSH) was used. All references in the retrieved articles were screened for further papers. From all the references we excluded

Results

More than 600 scientific references were considered because they deal with the human effects of cocaine used during pregnancy, with an exponential growth in number of papers published in recent years. Of these, 516 studies were retrieved and, based on a review of their methods sections, only 36 studies met the inclusion criteria for this analysis. Of these 36 studies, 3 studies [6], [7], [8] were excluded after a more detailed analysis because in these studies there were multiple exposures in

Discussion

Because very large numbers of women in the reproductive age group consume cocaine, there are serious concerns regarding the long term health of millions of children exposed in utero to this recreational drug [2]. An issue widely recognized by researchers and clinicians is that, in addition to cocaine, many other risk factors occur and may adversely affect infants exposed in utero to cocaine. These include other drugs of abuse and cigarettes, alcohol, poor prenatal care, single motherhood, and

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