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

Abstract

IMPORTANCE There is conflicting evidence on the association between intrapartum epidural analgesia and risk of autism spectrum disorder (ASD) in offspring.OBJECTIVE To evaluate the association between intrapartum epidural analgesia and the risk of ASD in offspring. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study was conducted inOntario, Canada, using the health and administrative records of singleton live births by vaginal delivery between April 1, 2006, and March 31, 2014. Neonates with less than 24 weeks' gestation or weighing less than 500 g were excluded. Offspring were followed up from 18 months of age until ASD diagnosis, loss to follow-up, or the end of the study (December 31, 2020), whichever occurred first. Exposure, covariate, and outcome data were obtained using provincial health administrative databases.EXPOSURES Any intrapartum exposure to epidural or combined spinal-epidural analgesia. MAIN OUTCOMES AND MEASURESThe primary outcome was ASD diagnosis after 18 months of age. Inverse probability of treatment weighting (IPTW) of Cox proportional hazards regression models was used to estimate the hazard ratio (HR) of intrapartum epidural analgesia and ASD in offspring. Offspring head injury was used as a control outcome. Models were adjusted for maternal sociodemographic factors, health behaviors, and medical and obstetrical history as well as labor, delivery, and offspring characteristics. Post hoc analyses included restriction to term neonates, a conditional within-mother analysis, exclusion of records with concomitant intrapartum pain management exposures, a complete case analysis, use of an alternative ASD definition, and estimation of the average treatment effect in the treated group. RESULTS Among the 650 373 mother-offspring pairs included in the study, 418 761 (64.4%) were exposed to intrapartum epidural analgesia. The mean (SD) maternal age at delivery was 29.7 (5.5) years; the offspring had a mean (SD) gestational age at delivery of 39.1 (1.6) weeks and included 329 808 male newborns (50.7%). The exposed and unexposed groups were similar in all maternal and newborn characteristics after IPTW (standardized difference <0.10). Autism spectrum disorder was diagnosed in 7546 offspring (1.8%) of mothers who received intrapartum epidural analgesia (incidence rate, 18.8 [95% CI,] per 10 000 person-years) compared with 3234 offspring (1.4%) who were unexposed (incidence rate, 14.4 [95% CI, 13.9-14.9] per 10 000 person-years). The crude HR for ASD associated with intrapartum epidural analgesia was 1.30 (95% CI, 1.25-1.36), and the IPTW-adjusted HR was 1.14 (95% CI, 1.08-1.21). Results did not qualitatively differ in post hoc analyses. (continued) Key Points Question Is there an association between administration of intrapartum epidural analgesia and risk of autism spectrum disorder (ASD) in offspring? Findings In this cohort study of 650 373 mother-offspring pairs in Ontario, Canada, intrapartum epidural analgesia was statistically associated with a small increase in risk of ASD in o...

Does Intrapartum Epidural Analgesia Increase the Risk of Autism Spectrum Disorder in Offspring? Most Likely Not

“…The results from the study by Murphy and colleagues 4 are timely and important because they replicate the negligible association measure between intrapartum epidural analgesia and ASD in a population with a possibly different confounding structure than in previous research. 6 As shown by Straub and colleagues, 6 the pooled hazard ratio for ASD across recent studies conducted in the US, Denmark, and Canadian provinces other than Ontario was negligible (10% increased hazard).…”

“…Validation of outcome status is also crucial in establishing whether an exposure is associated with a particular outcome. In their work, Murphy and colleagues defined ASD as the presence of at least 1 relevant diagnosis code at hospital discharge, emergency department visit, or outpatient surgery or at least 3 diagnostic codes within the health insurance plan records. Furthermore, the authors applied an alternative ASD outcome definition to maximize the outcome specificity.…”

“…The study by Murphy and colleagues used region-wide administrative health care data in Ontario, Canada, to investigate the association between intrapartum epidural analgesia and risk for ASD. The study identified 650 373 mothers with singleton live births delivered vaginally between 2006 and 2014.…”

“…Despite its weaknesses and limitations, the collective body of evidence from epidemiologic studies supports the notion that there is no meaningful association between intrapartum epidural analgesia for vaginal delivery and ASD in offspring. This latest research by Murphy and colleagues consolidates this conclusion and provides additional reassurance to pregnant patients and health care practitioners.…”

Comparison between neonatal outcomes of labor and delivery with labor neuraxial analgesia and without analgesia: A propensity score‐matched study

“…Recent observational studies have suggested that LNA may alter physiological functions in the developing brain and potentially lead to autism spectrum disorders. 3,4 Although the association between LNA and long-term neurodevelopmental disability remains controversial, 5,6 it is important to understand the potential effects of LNA on neonatal neurophysiological functions. May clinicians would agree that it is rational to predict long-term consequence from the short-term status.…”