Maternal-offspring microbiome interface contributes to the impact of maternal use of central nervous system-active drugs on offspring neurodevelopment.

The prevalence of maternal central nervous system-active medication use has increased over the last two decades, raising questions regarding potential neurodevelopmental consequences for offspring. While most of these substances are known to cross the placenta and enter breast milk, their developmental impact remains unclear. This review synthesizes current evidence identifying the maternal-offspring microbiome interface as a possible conduit for neurodevelopmental programming. We examine how the maternal gut, placental, and breast milk microbiomes establish the foundation for the offspring's early microbial ecosystem, how drug-induced dysbiosis may disrupt these interactions, and how these may impact offspring neurodevelopment. However, isolating specific drug-induced microbial effects from the influence of underlying maternal psychiatric conditions and identifying specific microbial signatures that correlate with resilience or susceptibility in offspring remain a substantial challenge. Current literature relies heavily on preclinical models, highlighting an urgent need for longitudinal human studies to better inform risk-benefit analyses for maternal pharmacotherapy.