Association Between Epidural Analgesia During Labor and Risk of Autism Spectrum Disorders in Offspring

Abstract

(Abstracted from JAMA Pediatr 2020;174(12):1168–1175) More than 70% of pregnant women receive neuraxial anesthesia to manage labor pain in the United States. However, its long-term effects on offspring are largely unknown.

Association of Epidural Analgesia in Women in Labor With Neonatal and Childhood Outcomes in a Population Cohort

“…12 More recently, a retrospective cohort study of 147 895 children showed a 37% relative increase in the risk of autism in babies whose mothers had epidural analgesia in labor. 13 This report stimulated debate and statements from professional societies regarding the likelihood of residual confounding and the lack of causal analysis. 14,15 A subsequent Canadian population-based study of 123 175 offspring found…”

“…5 However, the evidence was judged to be of overall low quality, limited by study inconsistency, imprecision in effect size estimates, and possible publication bias. 5 A controversial study 13 indicating an association between epidurals and risk of autism was criticized by 5 medical societies for significant methodological limitations, including the likelihood of residual confounding, and the findings of that study cannot be considered causal. [13][14][15] A subsequent Canadian population-based study, 16 which performed robust and extensive correction for confounding variables, found no association between labor epidural and autism.…”

“…5 A controversial study 13 indicating an association between epidurals and risk of autism was criticized by 5 medical societies for significant methodological limitations, including the likelihood of residual confounding, and the findings of that study cannot be considered causal. [13][14][15] A subsequent Canadian population-based study, 16 which performed robust and extensive correction for confounding variables, found no association between labor epidural and autism. Statements from the American Society of Anesthesiologists and the Royal College of Anaesthetists emphasize that the analgesia currently offered to women in labor should not be altered on the basis of these findings.…”

Evidence Mounts Refuting an Association Between Epidural Use and Neurodevelopmental Adverse Outcomes in Children

“…3 A recent population-based study of 147 895 live births in Kaiser Permanente Southern California hospitals reported that epidural pain relief is associated with a 37% increased risk of autism spectrum disorder in offspring. 4 However, residual confounding likely explains these findings, as a subsequent population-based study of 123 175 live births in Manitoba, Canada, did not confirm this association after accounting for a larger set of confounders. 5 Therefore, there is a need for more research that addresses selection and confounding bias to clarify the presence and extent of an association.Because assigning women to receive epidural pain relief or placebo in a randomized trial is unethical and immoral, high-quality longitudinal studies remain the only viable option for evaluating potential…”

Evaluation of Epidural Analgesia Use During Labor and Infection in Full-term Neonates Delivered Vaginally

“…Epidural analgesia provides effective relief of labor pain, but the associations between epidural analgesia and maternal and neonatal morbidity are controversial. 1,[3][4][5][6][7][8][9] The risk of maternal fever is 4-fold higher in women receiving epidural analgesia, [10][11][12][13] but the associations of neonatal outcomes with epidural analgesia-associated maternal fever vary. [14][15][16] In addition, placental infection, like histologic chorioamnionitis, is associated with epidural analgesia use and may cause intrauterine infection.…”