Elizabeth Wall-Wieler1,2, Brian T Bateman3, Ana Hanlon-Dearman4, Leslie L Roos1,2, Alexander J Butwick5. 1. Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. 2. Manitoba Centre for Health Policy, University of Manitoba, Winnipeg, Manitoba, Canada. 3. Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, Massachusetts. 4. Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada. 5. Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Stanford, California.
Abstract
Importance: Epidural labor analgesia (ELA) has been associated with an increased offspring risk of autism spectrum disorder (ASD). Whether this finding may be explained by residual confounding remains unclear. Objective: To assess the association between ELA and offspring risk of ASD. Design, Setting, and Participants: Longitudinal cohort study of vaginal deliveries of singleton live infants born from 2005 to 2016 from a population-based data set linking information from health care databases in Manitoba, Canada; offspring were followed from birth until 2019 or censored by death or emigration. Data were analyzed from October 19, 2020, to January 22, 2021. Exposures: Epidural labor analgesia. Main Outcomes and Measures: At least 1 inpatient or outpatient diagnosis of ASD in offspring aged at least 18 months. For the full population and a sibling cohort, inverse probability of treatment-weighted Cox proportional hazards regression analyses were used to control for potential confounders. Results: Of the 123 175 offspring included in this study (62 647 boys [50.9%]; mean [SD] age of mothers, 28.2 [5.8] years), 47 011 (38.2%) were exposed to ELA; 2.1% (985 of 47 011) of exposed vs 1.7% (1272 of 76 164) of unexposed offspring were diagnosed with ASD in the follow-up period (hazard ratio [HR], 1.25; 95% CI, 1.15-1.36). After adjusting for maternal sociodemographic, prepregnancy, pregnancy, and perinatal covariates, ELA was not associated with an offspring risk of ASD (inverse probability of treatment-weighted HR, 1.08; 95% CI, 0.97-1.20). In the within-siblings design adjusting for baseline covariates, ELA was not associated with ASD (inverse probability of treatment-weighted HR, 0.97; 95% CI, 0.78-1.22). Results from sensitivity analyses restricted to women without missing data who delivered at or after 37 weeks of gestation, firstborn infants only, and offspring with ASD classified with at least 2 diagnostic codes were consistent with findings from the main analyses. Conclusions and Relevance: In a Canadian population-based birth cohort study, no association between ELA exposure and an increased offspring risk of ASD was found.
Importance: Epidural labor analgesia (ELA) has been associated with an increased offspring risk of autism spectrum disorder (ASD). Whether this finding may be explained by residual confounding remains unclear. Objective: To assess the association between ELA and offspring risk of ASD. Design, Setting, and Participants: Longitudinal cohort study of vaginal deliveries of singleton live infants born from 2005 to 2016 from a population-based data set linking information from health care databases in Manitoba, Canada; offspring were followed from birth until 2019 or censored by death or emigration. Data were analyzed from October 19, 2020, to January 22, 2021. Exposures: Epidural labor analgesia. Main Outcomes and Measures: At least 1 inpatient or outpatient diagnosis of ASD in offspring aged at least 18 months. For the full population and a sibling cohort, inverse probability of treatment-weighted Cox proportional hazards regression analyses were used to control for potential confounders. Results: Of the 123 175 offspring included in this study (62 647 boys [50.9%]; mean [SD] age of mothers, 28.2 [5.8] years), 47 011 (38.2%) were exposed to ELA; 2.1% (985 of 47 011) of exposed vs 1.7% (1272 of 76 164) of unexposed offspring were diagnosed with ASD in the follow-up period (hazard ratio [HR], 1.25; 95% CI, 1.15-1.36). After adjusting for maternal sociodemographic, prepregnancy, pregnancy, and perinatal covariates, ELA was not associated with an offspring risk of ASD (inverse probability of treatment-weighted HR, 1.08; 95% CI, 0.97-1.20). In the within-siblings design adjusting for baseline covariates, ELA was not associated with ASD (inverse probability of treatment-weighted HR, 0.97; 95% CI, 0.78-1.22). Results from sensitivity analyses restricted to women without missing data who delivered at or after 37 weeks of gestation, firstborn infants only, and offspring with ASD classified with at least 2 diagnostic codes were consistent with findings from the main analyses. Conclusions and Relevance: In a Canadian population-based birth cohort study, no association between ELA exposure and an increased offspring risk of ASD was found.
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