Exposure to anesthesia during delivery and risk of autism spectrum disorder: A retrospective cohort study

INTRODUCTION: Despite the growing use of pain management during delivery, evidence regarding the association between different modes of obstetric anesthesia and autism spectrum disorder in offspring is mixed. MATERIAL AND METHODS: We conducted a retrospective cohort study of 98 630 singleton live births at a single hospital (2011-2019), with follow-up through January 2023. Participants were grouped by delivery and anesthesia type: (1) vaginal delivery without analgesia, (2) vaginal delivery with epidural, (3) cesarean with neuraxial anesthesia, and (4) cesarean with general anesthesia. Autism spectrum disorder (ASD) diagnosis was the primary outcome. Kaplan-Meier plots and Cox regression were used to assess cumulative incidence and hazard ratios. RESULTS: Of the cohort (51.2% male, 62.0% Bedouin), 21.2% were born by vaginal delivery with epidural, 3.8% by cesarean with neuraxial anesthesia, and 11.4% by cesarean with general anesthesia. Cumulative ASD incidence was higher in all exposure groups (vaginal delivery with epidural: 1.25%, cesarean with neuraxial anesthesia: 1.56%, cesarean with general anesthesia: 1.50%) than in vaginal delivery without analgesia (0.55%). Nevertheless, after adjustment for covariates, only cesarean with general anesthesia was significantly associated with increased ASD risk (aHR = 1.571; 99% CI: 1.12-2.22). CONCLUSIONS: These findings suggest that general anesthesia during cesarean delivery, but not neuraxial anesthesia or epidural use, might be associated with ASD risk. Further studies are needed to understand the underlying mechanisms.