Gender Differences in the Outcome of Offspring Prenatally Exposed to Drugs of Abuse

Abstract

Despite great efforts to warn pregnant women that drugs of abuse impact development of the embryo and the fetus, the use of legal and illegal drugs by childbearing women is still a major public health concern. In parallel with well-established teratogenic effects elicited by some drugs of abuse, epidemiological studies show that certain psychoactive substances do not induce birth defects but lead to subtle neurobehavioral alterations in the offspring that manifest as early as during infancy. Although gender differences in offspring susceptibility have not been fully investigated, a number of longitudinal studies indicate that male and female progeny exposed in utero to drugs of abuse show different vulnerabilities to deleterious effects of these substances in cognitive, executive, and behavioral domains. Here, we briefly review the existing literature focusing on gender differences in the neurobehavioral consequences of maternal exposure to drugs of abuse. Overall, the data strongly indicate that male exposed progeny are more susceptible than female to dysfunctions in cognitive processing and emotional regulation. However, insights into the mechanisms determining this natural phenomenon are not currently available. Our analysis prompts future investigations to implement clinical studies including the influence of gender/sex as a biological variable in the outcome of offspring prenatally exposed to drugs of abuse.

Keywords: development; drugs of abuse; gender; neuropsychiatric; prenatal; sex; vulnerability.

FIGURE 1

Heatmaps of neurobehavioral outcomes collectively identified as cognitive deficits (including executive function), ADHD risk, and behavioral problems, with missing information on gender differences shown in gray. Outcome intensities are displayed as colors ranging from pink (female) to blue (male) shown in the key. Gender differences were not observed in executive functions during childhood in offspring prenatally exposed to cocaine in one study only (Accornero et al., 2007); therefore, the heatmap displays blue as a result of the larger number of consistent studies reporting that boys are more susceptible to exhibit deficits in cognitive abilities when compared to girls (see text and also Table 1).