Association of Neuraxial Labor Analgesia for Vaginal Childbirth With Risk of Autism Spectrum Disorder

Abstract

IMPORTANCERecent studies have reported conflicting findings regarding a potential association between analgesia used during labor and autism spectrum disorder in the offspring. OBJECTIVE To evaluate whether neuraxial labor analgesia increases the risk of autism spectrum disorder in the offspring. DESIGN, SETTING, AND PARTICIPANTS 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. EXPOSURES Presence of a procedure code indicating neuraxial labor analgesia. MAIN OUTCOMES AND MEASURESChildren 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. RESULTSThe 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 motherchild 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).

Is There an Association between the Use of Epidural Analgesia during Labor and the Development of Autism Spectrum Disorder in the Offspring?—A Review of the Literature

“…The last two studies by Hanley et al and the most recently published by Straub et al demonstrated a small increase in the risk of ASD in the offspring exposed to ELA [ 15 , 18 ]. The first study included 388,254 term singleton vaginal deliveries in British Columbia, Canada between 1 April 2000, and 31 December 2014, with the follow-up up to 31 December 2016.…”

“…The research by Qiu et al which reported 37% increase in the risk of ASD development in the offspring exposed to ELA is so far the only study to prove significant association. The later published five cohort studies reported HRs between 1.05 and 1.11 with pooled adjusted HR of 1.07 reflecting a lack of significant interrelation [ 18 ]. The study by Qiu et al was widely criticized and many limitations were identified by the experts.…”

Exposure to Intrapartum Epidural Analgesia and Risk of Autism Spectrum Disorder in Offspring

“…15 In addition, a nationwide cohort study of public and private US insurance records reported a small risk increase (aHR, 1.08; 95% CI, 1.02-1.15). 18 Its authors also reported the pooled effect estimate from a metaanalysis they conducted of published cohort studies (aHR, 1.10; 95% CI, 1.06-1.13). 18 Despite the use of similar case-finding algorithms, covariates, and post hoc analyses, the differences in findings across the Canadian and Danish studies highlight the challenges of comparing the results from disparate administrative data sources.…”

“…18 Its authors also reported the pooled effect estimate from a metaanalysis they conducted of published cohort studies (aHR, 1.10; 95% CI, 1.06-1.13). 18 Despite the use of similar case-finding algorithms, covariates, and post hoc analyses, the differences in findings across the Canadian and Danish studies highlight the challenges of comparing the results from disparate administrative data sources. Regional variations in how ASD diagnoses are captured and the quality and quantity of exposure and covariate data are all likely to change the magnitude and direction of reported associations.…”

Perinatal Anesthesia Exposure and Autism Spectrum Disorders

“…Straub et al 18 published a study with over 1.6 million subjects, the largest sample size compared with the beforementioned studies. This study used a propensity matching score to control for confounders; it also showed no association between increased risk of ASD and the use of epidural labor analgesia.…”