Elsevier

Neurotoxicology and Teratology

Volume 27, Issue 2, March–April 2005, Pages 221-229
Neurotoxicology and Teratology

Marijuana impairs growth in mid-gestation fetuses

https://doi.org/10.1016/j.ntt.2004.11.002Get rights and content

Abstract

Marijuana (Cannabis sativa) is the most commonly used illicit drug by pregnant women, but information is limited about the effects of prenatal cannabis exposure on fetal development. The present study evaluated the influence of early maternal marijuana use on fetal growth. Women electing voluntary saline-induced abortions were recruited at a mid-gestational stage of pregnancy (weeks 17–22), and detailed drug use and medical histories were obtained. Toxicological assays (maternal urine and fetal meconium) were used in conjunction with the maternal report to assign groups. Subjects with documented cocaine and opiate use were excluded. Main developmental outcome variables were fetal weight, foot length, body length, and head circumference; ponderal index was also examined. Analyses were adjusted for maternal alcohol and cigarette use. Marijuana (n=44)- and nonmarijuana (n=95)-exposed fetuses had similar rates of growth with increased age. However, there was a 0.08-cm (95% CI −0.15 to −0.01) and 14.53-g (95% CI −28.21 to 0.86) significant reduction of foot length and body weight, respectively, for marijuana-exposed fetuses. Moreover, fetal foot length development was negatively correlated with the amount and frequency of marijuana use reported by the mothers. These findings provide evidence of a negative impact of prenatal marijuana exposure on the mid-gestational fetal growth even when adjusting for maternal use of other substances well known to impair fetal development.

Introduction

Cannabis is the most commonly used illegal drug among young women of childbearing age in most western societies. For example, 13–23% of females aged 16–24 report marijuana use in the UK [4]. Approximately 4% of women in the USA report using illicit drugs (i.e., marijuana, cocaine, heroin, hallucinogens, inhalants, nonmedical psychotherapeutic) during pregnancy, with marijuana being the most commonly (75%) used drug among pregnant women [43]. Significant advances have been made in recent years as to the biology of the cannabis system, including identification of the cannabis receptors, their distribution in the brain and periphery, pharmacology, and signaling pathways [28], [40]. Despite the growing interest in the biological actions of cannabis, there are still only few studies regarding the consequences of cannabis exposure, especially in relation to the development of the human fetus. Such information is essential when considering the current debates as to the potential legalization of marijuana in many western societies and the establishment of national policies related to marijuana's effects on health.

Prenatal effects of maternal drug use on fetal development are primarily assessed by measures of fetal growth. There is evidence in the literature that marijuana-exposed infants at birth have reduced weight [15], [21], [25], [50] and/or head circumference [15], [19], as well as decreased gestation length [6], [20], [21], [25]. These findings are not, however, unequivocal since some studies have failed to document significant effects of in utero cannabis exposure on fetal development [17], [39] or gestation length [32], [48]. There has also been a report of increased birthweight in association with prenatal marijuana use, primarily associated with marijuana use during the third trimester [8]. Multiple reasons could account for the discrepant findings, such as the stringency of the control group, the accuracy of drug use, genetic and social differences of the populations investigated, and the developmental time period when growth parameters are evaluated. Another important consideration for the conflicting results in the literature may relate to confounding effects of maternal use of other drugs, such as cigarette and alcohol. Animal studies in which experimental conditions can be well controlled have documented reduced weight in association with prenatal cannabis exposure [1], [3], thus substantiating the findings in humans of a negative impact of maternal marijuana use on fetal growth. The potential long-term prenatal effects of marijuana exposure have also been examined in longitudinal studies. Such investigations have documented specific abnormalities in cognitive (e.g., verbal skills, memory) and behavioral (impulsivity, inattention, social disturbances) functioning in offspring of women who used marijuana during pregnancy [14], [18], [22], [41].

Despite increasing evidence of developmental impairment, as well as behavioral disturbances with in utero marijuana exposure, there is still a virtual lack of information as to the influence of early prenatal marijuana exposure on human fetal growth. Only few studies to date have investigated the prenatal effects of marijuana, and those have mainly evaluated newborns, which make it difficult to dissociate the influence of early versus late in utero drug exposure. Since women are more likely to discontinue their drug use during the early stages of pregnancy, evaluation of an early to mid-developmental time period is of particular importance. To assess developmental events prior to the third trimester, the current project examined standard measures of development in aborted fetuses. The study focused on the early to mid-gestation (weeks 17–22) developmental period since it is the latest stage during which normal specimens can be obtained from voluntary abortions. Thus, in comparison to most investigations that have examined the cumulative impact of cannabis exposure throughout the entire prenatal developmental period, the present study sought to identify the influence of early to mid-gestational marijuana exposure on fetal growth. We hypothesized that indices of fetal growth, particularly body weight, would be reduced in association with maternal marijuana use during early to mid-gestation pregnancy.

Section snippets

Sample collection

Pregnant women who had elected to carry out a voluntary saline-induced abortion at Kings County Hospital, Brooklyn, NY, between January 2000 and December 2002 were the focus group of the project. The study was approved by the Institutional Review Boards of Kings County Hospital Center and SUNY Downstate. Women were recruited for the study if they were estimated (based on ultrasound and/or maternal physical exam) to be at a mid-gestational stage (weeks 17–22) of pregnancy. The women provided

Maternal characteristics of the marijuana-exposed and nonexposed groups

There was an approximately 30% refusal rate for participation in the study by pregnant women who fulfilled the project criteria. A total of 139 subjects gave informed consent, completed the questionnaire, and were included in the study (demographics in Table 1). In this cohort, 31.7% had evidence, from either toxicology and/or maternal report, of marijuana use during pregnancy. Of the women in the cannabis-use group who admitted marijuana intake, 81.8% reported using marijuana at a rate of

Discussion

Consistent with previous evaluations of the trend of drug use in the innercity community currently investigated [35], pregnant women in this population had a high rate of marijuana use (31.6%) with a lower incidence of cocaine (4%) and opiate (2.2%) intake. The high use of marijuana in many communities [4], [43] is disturbing in light of the current findings revealing an adverse influence of early prenatal cannabis exposure on various indices of fetal growth. Despite the strong correlations

Acknowledgements

We thank Alexandra Guilliume and Dionne Dunkley for their valuable assistance with the maternal interviews and handling of the fetal specimens. We are also grateful for the statistical assistance provided by the staff at the Statistical Department at the Karolinska Institute. The study was funded by the National Institutes of Health (NIDA DA12030).

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