Maternal epidural analgesia use during labor and delivery is associated with a small increase in the risk for autism spectrum disorder (ASD) in offspring. However, interpretation of these findings are likely limited by residual confounding with study data not providing strong evidence for the association. These are the results of a Canadian study published in JAMA.
Epidural analgesia has a good safety and efficacy profile for alleviating labor pain more effectively than opioids, but data on the long-term outcomes associated with epidural analgesia is limited. Previous research on epidural analgesia use during labor and delivery and the risk for ASD in children has produced conflicting results. The objective of the current study was to assess detail antenatal care and labor and delivery data tied to ASD diagnoses to determine whether maternal epidurals are associated with ASD risk in offspring in a population-based study.
The retrospective cohort study included women who delivered a live singleton term infant in British Columbia, Canada, from April 1, 2000, to December 31, 2014. All children were followed up until a clinical diagnosis of ASD, death, study conclusion on December 31, 2016, or until they moved outside the province. The British Columbia Autism Assessment Network and the British Columbia Ministry of Education were used to obtain clinical ASD diagnostic data.
The overall cohort included 599,527 singleton births from 386,192 women. After exclusions, the main cohort included 388,254 vaginal deliveries to 258,472 women, of which 111,480 infants (28.71%) were born to women who used epidural analgesia during labor and delivery. The mean (SD) age for women exposed to epidural analgesia was 29.9 (5.5), compared with 30.1 (5.5) for those not exposed. The children were followed for a mean of 9.05 years (4.3 years).
A total of 5192 children (1.34%) had been diagnosed with ASD after follow-up concluded on December 31, 2016. ASD was diagnosed in 1710 children (1.53%) from the 111,480 deliveries exposed to epidural analgesia (94,157 women), compared with an ASD diagnosis in 3482 children (1.26%) from the 276,774 deliveries not exposed to epidural analgesia (192,510 women) (absolute risk difference, 0.28% [95% CI, 0.19%-0.36%]).
The hazard ratio (HR) was 1.32 (95% CI, 1.24-1.40) for the association between ASD and exposure to epidural analgesia in the unadjusted analysis. In the fully adjusted analysis that also accounted for induction of labor, gestational age, sex, status of small or large for gestational age at birth, and congenital anomaly, further attenuation was observed (fully adjusted HR, 1.09 [95% CI, 1.00-1.15]).
No statistically significant association was observed regarding epidural analgesia use during labor and delivery with ASD for the within-woman matched conditional logistic regression (839/1659 [50.6%] in the exposed group vs 1905/4587 [41.5%] in the unexposed group; fully adjusted hazard ratio, 1.07 [95% CI, 0.87-1.30]).
Study limitations included the observational design, and the important differences that occurred between deliveries in which epidural analgesia was used and not used, especially for variables that suggest a worse prognosis for women exposed to epidural analgesia. In addition, detailed information was lacking for the dose of epidural analgesia to directly address the dose-response relationship.
“Given the likelihood of residual confounding that may account for the results, these findings do not provide strong supporting evidence for this association,” stated the researchers. “Moreover, there was no statistically significant association between epidural analgesia and ASD in the within-mother matched analysis or the sibling cohort.”
Hanley GE, Bickford C, Ip A, et al. Association of epidural analgesia during labor and delivery with autism spectrum disorder in offspring. JAMA. Published online September 28, 2021. doi: 10.1001/jama.2021.14986