Potential Mechanism Connecting Preeclampsia to Autism Spectrum Disorder in Offspring: The Role of Microglial Abnormalities

Abstract

Preeclampsia (PE) is a serious complication of pregnancy characterized by chronic inflammation and immune dysregulation, which significantly increases the risk of neurodevelopmental disorders in offspring, including the autism spectrum disorder (ASD). This review investigated the potential mechanisms linking PE to ASD, with a particular focus on the role of microglial abnormalities. Epidemiological studies have revealed that prenatal exposure to PE raised the risk of ASD, with affected offspring showing increased odds ratios. Microglia, the prime resident immune cells of the central nervous system (CNS), are critical for normal neurodevelopment, influencing processes such as neural stem cell (NSC) proliferation, synaptic pruning, and normal function of the neural circuit. Early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) may have an impact on the microglia abnormality and ASD through not exactly same pathway. Postmortem studies of ASD have further revealed increased microglial density, altered microglial morphology, and upregulated inflammatory markers in key brain regions, including the hippocampus and prefrontal cortex. Understanding the complex processes and potential mechanisms between EOPE, LOPE, microglial abnormalities, and ASD pathogenesis may highlight the importance of early screening and intervention for children born to mothers with PE. Targeting microglia-mediated pathways may offer novel therapeutic strategies to reduce the risk of ASD in these vulnerable populations.

Keywords: autism spectrum disorder; microglia; neurodevelopmental disorders; pre-eclampsia; prenatal exposure delayed effects.