Abstract
BACKGROUND: The effect of labor epidural anesthesia (LEA) on the risk of autism spectrum disorder (ASD) in offspring has been investigated recently, and available results are inconsistent. METHODS: We searched the PubMed and EMBASE databases for relevant studies and performed a systematic review and meta-analysis of the literature. Subgroup analyses were conducted to assess the sources of heterogeneity. Both fixed and random effects models were used was used to estimate overall relative risk. RESULTS: Our results showed that LEA was associated with an increased risk of ASD in offspring [HR = 1.3, 95% confidence interval (CI): 1.25-1.35; P < 0.001] after combining crude estimates from the included studies. This association was gradually reduced, but still statistically significant, when potential confounding factors were considered (HR 1.13, 95% CI 1.03-1.25, P = 0.014). However, there was no significant association when we combined data of siblings from other pregnancies (HR = 1.07, 95% CI: 0.99-1.16, P = 0.076), implying that the association was due to confounding factors. CONCLUSION: The statistically significant association between LEA and ASD in the offspring can be partially explained by unmeasured confounding. SYSTEMATIC REVIEW REGISTRATION: Identifier CRD42022302892.