Developmental consequences of fetal exposure to drugs: what we know and what we still must learn

Abstract

Most drugs of abuse easily cross the placenta and can affect fetal brain development. In utero exposures to drugs thus can have long-lasting implications for brain structure and function. These effects on the developing nervous system, before homeostatic regulatory mechanisms are properly calibrated, often differ from their effects on mature systems. In this review, we describe current knowledge on how alcohol, nicotine, cocaine, amphetamine, Ecstasy, and opiates (among other drugs) produce alterations in neurodevelopmental trajectory. We focus both on animal models and available clinical and imaging data from cross-sectional and longitudinal human studies. Early studies of fetal exposures focused on classic teratological methods that are insufficient for revealing more subtle effects that are nevertheless very behaviorally relevant. Modern mechanistic approaches have informed us greatly as to how to potentially ameliorate the induced deficits in brain formation and function, but conclude that better delineation of sensitive periods, dose-response relationships, and long-term longitudinal studies assessing future risk of offspring to exhibit learning disabilities, mental health disorders, and limited neural adaptations are crucial to limit the societal impact of these exposures.

Figure 1

Major neurodevelopmental events across species. Schematic diagram that aligns human brain development with several animal models (monkey, rabbit, rat, and mouse) often used in studies of fetal drug exposure. Note in particular that the rodent equivalent of third trimester fetal development occurs postnatally.

Figure 2

Biological targets of fetal drug exposures. Drugs of abuse not only target the developing fetal brain directly, but can exert effects through a variety of organs with the mother, including the uterus, placenta, heart, lungs, and brain.

Figure 3

Schematic summary of effects of distinct drug classes on offspring development. A wide variety of significant structural and neurobehavioral deficits are induced by fetal exposures to abused substances. As described in the text, the drug class, timing, dose, and pattern of intake all substantially determine the long-term effects on the developing child.