Association of intrapartum epidural analgesia and oxytocin exposure with offspring autism and neurodevelopment from the Japan Environment and Children’s Study

Given the increasing prevalence of neurodevelopmental disorders, this study examined the association between autism and neurodevelopmental delays and exposure to intrapartum labor epidural analgesia (LEA) and synthetic oxytocin (OT) in offspring. The data were obtained from various questionnaires, including the Japanese Ages and Stages Questionnaires, Third Edition. Using data from a large-scale longitudinal birth cohort study in Japan, 72,801 participants were enrolled and follow-up to age 4 years. Exposure during labor was categorized into four groups: no-exposure, OT, LEA, and LEA-OT. Adjusted odds ratios for autism were 2.35 (95% CI 1.44-3.83) in the LEA-OT group and 2.41 (95% CI 1.31-4.45) in the LEA group. The E-values for the point estimates were 4.16 in the LEA-OT group and 4.29 in the LEA group, and those for the lower limits of the 95% confidence intervals were 2.39 and 2.05, respectively, indicating only moderate robustness to unmeasured confounding. Associations with autism were consistent across analyses in the LEA-OT group, but in sex-stratified analyses, only males showed an association. No consistent associations with neurodevelopmental delays were observed in any exposure groups. Since residual confounding cannot be excluded, with limited external validity, these findings warrant replication in independent cohorts to clarify causality.