Advancing understanding of the mechanisms of autism spectrum disorder through perinatal risk factors.

Advances in elucidating the genetic etiology of autism spectrum disorder (ASD) have significantly enhanced our understanding of its neurodevelopmental underpinnings. However, given the considerable heterogeneity and complexity of ASD, environmental factors also play a critical role in affecting the fetus directly or interacting with genetic susceptibilities to contribute to ASD-related developmental impairments. Epidemiological studies indicate that children exposed to perinatal complications, such as gestational diabetes, birth asphyxia, and preeclampsia, have a higher likelihood of being diagnosed with ASD. In this review, we summarize current evidence on perinatal risk factors associated with ASD. Insights integrated from epidemiological, epigenetic, neuropathological, and animal model studies help clarify the underlying pathophysiology of the disorder. These findings, reflecting the intricate interplay between genetic and environmental mechanisms in ASD, also point to potential targets for early intervention strategies.