Reference: JAMA Pediatr. 2020 Oct 12
Although the etiology of autism spectrum disorders (ASD) is acknowledged to be multifactorial, and at least partly genetically-mediated, there have been recent controversial publications reporting an association between exposure to general anesthesia during caesarean sections and autism. This month, a group from Kaiser Permanente in California reported an association between maternal labor epidural analgesia (LEA) and development of ASD in a retrospective cohort analysis of almost 150,000 babies born between 2008 and 2015. Vaginal birth with LEA is the most common method of childbirth in many developed countries.
The authors used medical record review to look at babies born vaginally in the Kaiser system and followed them into childhood, gathering coding information about the use and duration of epidural analgesia along with coding for ASD in the first few years of the child’s life. The authors determined that mothers who had epidural analgesia tended to have higher income and education levels, were more likely to be White, and also gave birth to slightly larger and gestationally older babies who were more likely to be diagnosed with a birth defect. After using Cox regression analysis to adjust for confounders such as age, smoking status, birth defects, and a number of other factors, there was an association with exposure to LEA versus no LEA and ASD (adjusted hazard ratio [HR] 1.37, 95% CI 1.23-1.53). In fact, they discovered a biologic gradient wherein the longer the mother was exposed to LEA, the higher the hazard of ASD; < 4 hours corresponded to an absolute risk of 1.6% and adjusted HR of 1.33, 4-8 hours to an absolute risk of 1.8% and adjusted HR of 1.35, and > 8 hours to an absolute risk of 2.2% and adjusted HR of 1.46.
The study has limitations. There are a LOT of potential confounders here, and one thing we can be certain of is that they were not all measured. For example, there are a variety of reasons why LEA is chosen to manage labor pain, and the authors do not report data on perinatal course or labor duration. A more difficult labor may be associated with both a greater need for LEA and adverse perinatal or developmental outcomes.
The study authors state that “our findings raise the concern that [even] the short duration of LEA exposure may be associated with long-term neurodevelopmental disorders.” Specialty organizations have been quick to point out that association does not mean causation. Given the limitations of the analysis, this weak association should be considered hypothesis-generating rather than practice-changing. An unmeasured confounder might be simultaneously increasing the risk of both ASD and LEA; in this situation, the sequence is not necessarily evidence of causality.
For more information, see the topic Autism Spectrum Disorders in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Dan Randall, MD, Deputy Editor for Internal Medicine at DynaMed. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School, and Katharine DeGeorge, MD, MS, Associate Professor of Family Medicine at the University of Virginia and Clinical Editor at DynaMed.