Association of Neuraxial Labor Analgesia for Vaginal Childbirth With Risk of Autism Spectrum Disorder
Authors: Loreen Straub, Krista F. Huybrechts, Helen Mogun, Brian T. Bateman
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Recent studies have reported conflicting findings regarding a potential association between analgesia used during labor and autism spectrum disorder in the offspring. <h3>Objective</h3> To evaluate whether neuraxial labor analgesia increases the risk of autism spectrum disorder in the offspring. <h3>Design, Setting, and Participants</h3> This cohort study included mother-child dyads who underwent vaginal delivery and were exposed to neuraxial labor analgesia. Delivery data were collected from the Medicaid Analytic eXtract (2005-2014) for mothers with public insurance and the IBM Health MarketScan Research Database (2005-2015) for mothers with private insurance. Data analysis was conducted from January to October 2021. <h3>Exposures</h3> Presence of a procedure code indicating neuraxial labor analgesia. <h3>Main Outcomes and Measures</h3> Children with autism spectrum disorder, identified using a validated algorithm (positive predictive value: 94% [95% CI, 83%-99%]). Cumulative incidence curves stratified by exposure were assessed using Kaplan-Meier analyses. Hazard ratios were estimated through Cox proportional hazards regression, using propensity-score fine stratification for confounding control. Estimates from both insurance cohorts were combined through fixed-effects meta-analysis. Subsequently, results from these analyses were combined with existing published studies. <h3>Results</h3> The cohort of mother-child dyads with public insurance consisted of 910 696 deliveries (mean [SD] maternal age, 24.3 [5.7] years; 286 025 [31.4%] Black mothers; 374 282 [41.1%] White mothers), with 484 752 (53.2%) being exposed to neuraxial labor analgesia. The cohort of mother-child dyads with private insurance included 696 883 deliveries (mean [SD] maternal age, 31.0 [4.5] years; race and ethnicity data not available), with 513 347 (73.7%) being exposed. Cumulative incidence of autism spectrum disorder by 10 years of age was 1.93% (95% CI, 1.73%-2.13%) among children in the exposed group vs 1.64% (95% CI, 1.51%-1.76%) among children in the unexposed group in the publicly insured cohort. Respective numbers were 1.33% (95% CI, 1.19%-1.46%) and 1.19% (95% CI, 0.99%-1.38%) in the privately insured cohort. Adjusting for potential confounders and pooling across both cohorts resulted in a hazard ratio of 1.08 (95% CI, 1.02-1.15). Results were consistent when additionally adjusting for empirically identified variables through high-dimensional propensity score analyses (pooled hazard ratio, 1.07; 95% CI, 1.00-1.14) or expanding the cohorts to include cesarean deliveries and assisted vaginal deliveries (pooled hazard ratio, 1.07; 95% CI, 1.03-1.12). Meta-analysis of this study and recently published observational studies yielded similar findings with a pooled hazard ratio of 1.10 (95% CI, 1.06-1.13). <h3>Conclusions and Relevance</h3> Although a small increase in risk cannot be ruled out, the combined evidence from observational studies does not support the notion that neuraxial labor analgesia is associated with an increased risk of autism spectrum disorder.