Abstract
Background: Prenatal exposure to maternal inflammation has been hypothesized to contribute to the etiology of autism spectrum disorder (ASD). However, individual studies have yielded inconsistent findings. This meta-analysis aimed to quantify the association between maternal inflammatory conditions during pregnancy and the risk of ASD in offspring.Methods: We systematically searched PubMed, Embase, and Web of Science from inception through December 2022 for observational studies examining maternal infection, fever, or inflammatory markers and ASD risk. Random-effects models were used to pool odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I² statistics, and subgroup analyses were performed by timing, type of inflammation, and study quality.Results: Twenty-three studies met inclusion criteria, comprising 1,892,345 participants. Maternal infection during pregnancy was associated with a significantly increased odds of ASD (OR = 1.32, 95% CI: 1.18–1.47, I² = 68%). Fever specifically showed a stronger effect (OR = 1.54, 95% CI: 1.28–1.86). Second-trimester exposure yielded the highest risk (OR = 1.48, 95% CI: 1.21–1.81). No significant publication bias was detected.Conclusions: Maternal inflammation, particularly infection and fever, is associated with a modest increase in ASD risk. These findings support the role of prenatal immune activation in neurodevelopmental disorders and highlight potential windows for intervention.