From decidua to brain: Immune pathways linking maternal infections to neurodevelopmental disorders in offspring

Abstract

Background: The decidua, a specialised endometrial tissue formed during pregnancy, balances maternal tolerance to the semi-allogeneic fetus with defence against pathogens; maternal infections disrupt this environment, triggering maternal immune activation, placental dysfunction, and adverse fetal neurodevelopment. Aim: To compare how human immunodeficiency virus (HIV), Zika virus, and cytomegalovirus (CMV) dysregulate the decidual microenvironment and how these disruptions contribute to adverse neurodevelopmental outcomes in offspring. Methods: A narrative review of the published literature was conducted, synthesising evidence on pathogen-specific effects on decidual immune regulation, maternal immune activation, placental dysfunction, epigenetic modifications, and neurodevelopmental outcomes. Results: HIV predominantly induces chronic systemic inflammation and placental insufficiency; Zika virus directly infects decidual and placental cells to breach the maternal–fetal barrier; and CMV exerts combined cytopathic and inflammatory effects. Despite distinct mechanisms, all three pathogens disrupt the decidual microenvironment and converge on epigenetic reprogramming as a shared molecular pathway linking prenatal immune challenge to persistent neurodevelopmental impairment. Conclusion: Comparative evaluation of pathogen-specific mechanisms clarifies how maternal infections influence fetal neurodevelopment and highlights shared and divergent targets for future preventive and therapeutic strategies. Relevance for patients: These findings may support earlier prenatal screening, informed clinical management of at-risk pregnancies, and interventions to reduce long-term neurodevelopmental disorders in exposed children.