Maternal Immune Activation and Neurodevelopmental Disorders: A Cross-Species Perspective

Prenatal exposure to infection increases the likelihood of neurodevelopmental disorders (NDDs). This association is attributed largely to the maternal inflammatory response, maternal immune activation (MIA), rather than to single pathogen. In this review, we discuss the molecular, cellular, and behavioral consequences of MIA and their contribution to NDDs in clinical cohorts and preclinical models across different species. We first trace the pathophysiology linking maternal infection to altered fetal neurodevelopment, describing how diverse immune challenges converge on shared nodes including cytokine signaling, oxidative and nutritional stress, placental dysfunction, and epigenetic modification. We then describe how these perturbations affect neural circuits and behavior, focusing on the disrupted social development. Next, we consider sources of individual variation, including gestational timing, fetal sex, and later-life "second hits," that may contribute to the greater vulnerability. Finally, we discuss the translational implications of this work in terms of maternal cytokine and epigenetic signatures as candidate biomarkers for risk stratification and potential therapeutic approaches.