Babies born to mothers who used epidural analgesia during labor were not at increased risk of developing autism spectrum disorder (ASD), according to a longitudinal cohort study from Canada.
Around 2.1% of children exposed to epidural labor analgesia (ELA) developed ASD, compared with 1.7% who were not exposed (HR 1.25, 95% CI 1.15-1.36), reported Elizabeth Wall-Wieler, PhD, of the University of Manitoba in Winnipeg, and colleagues.
But after adjusting for maternal sociodemographic, pre-pregnancy, pregnancy, and perinatal factors, the researchers found no association between epidural analgesia and childhood ASD risk (HR 1.08, 95% CI 0.97-1.20), they wrote in JAMA Pediatrics.
“This finding is of clinical importance in the context of pregnant women and their obstetric and anesthesia care professionals who are considering ELA during labor,” Wall-Wieler and colleagues noted.
The group’s results contradict a recent study from Qiu et al. that found a 37% increased risk of autism in kids whose mothers used epidural analgesia. This prior research did not account for key perinatal factors, including induction of labor, labor dystocia, and fetal distress, and was criticized by five medical societies for potential residual confounding.
Wall-Wieler and colleagues said that ELA is “recognized as the most effective method of providing labor analgesia,” adding that future qualitative research should assess how their findings — as well as the prior ones — have altered the perceptions about the perceived risk of ASD in offspring among both pregnant women and healthcare providers.
In an accompanying editorial, Gillian Hanley, PhD, of the University of British Columbia in Vancouver, and colleagues said that given the concerns stemming from previous findings, “it thus comes with some relief that Wall-Wieler et al found no association when controlling for key maternal sociodemographic and perinatal factors.”
However, they speculated about whether the absence of evidence marking an association between epidural analgesia and childhood autism should put clinicians at ease.
“Taken together, the articles by Qiu et al. and Wall-Wieler et al. offer an important opportunity to examine critical questions about the plausibility of associations between obstetric care during labor and delivery and ASD risk,” the editorialists wrote. These studies allow researchers to further examine methodological approaches, they added, acknowledging that the amount of anesthetic that enters the newborn brain, the biological plausibility of risk with specific neonatal factors, and how ASD is diagnosed may all influence these results.
“Epidural labor analgesia is an extremely effective approach to obstetric analgesia,” Hanley’s group noted. “We have a collective responsibility to understand whether it is a safe option that sets a healthy developmental pathway well into childhood.”
Dimitri Christakis, MD, MPH, editor-in-chief of JAMA Pediatrics, wrote in an editor’s note that the journal’s publication of two similar studies with conflicting results in such a short time period is testament to the imperfect and iterative nature of the scientific process.
“For now, my personal assessment is that the association is yet to be definitively established,” Christakis wrote. “If a more definitive study is done, JAMA Pediatrics will publish it.”
Epidural analgesia is used by 73% of pregnant women in the U.S. for pain during labor. As the U.S. incidence of ASD increased from 0.66% in 2002 to 1.85% in 2016, there has been more attention on identifying possible environmental factors that put children at risk, Wall-Wieler and colleagues said.
This longitudinal cohort study included vaginal deliveries of singleton babies born in Canada from 2005 to 2016. The group followed children from birth up until 2019. Information was obtained from a population-based dataset, linking healthcare information from four providers.
There were more than 123,000 infants included in the study; about 38% were exposed to epidural analgesia during delivery, and approximately 80,000 had a sibling in the study cohort. Mothers were a mean age of 28 years.
Births with epidural analgesia were more likely to be nulliparous, have premature rupture of membranes, antepartum hemorrhage, induction of labor, augmentation of labor, and fetal distress.
Most children with ASD received a diagnosis in the outpatient setting, with around 75% getting their first diagnosis from a pediatrician. The median age of kids at their first diagnosis was 4 years.
The researchers observed an association between ELA and autism risk before accounting for confounders; but after controlling for all maternal sociodemographic, pre-pregnancy, pregnancy and perinatal factors, there was no longer a correlation.
In an analysis of siblings, researchers again observed a null association after controlling for all confounders (HR 1.14, 95% CI 0.99-1.30) and family fixed effects (inverse probability of treatment-weighted HR 0.97, 95% CI 0.78-1.22). Siblings who were exposed to epidural analgesia had a 2% cumulative risk of developing autism, and unexposed siblings had a risk of 1.6%.
Wall-Wieler and colleagues noted that their findings may have been limited by the accuracy of inpatient and outpatient diagnostic codes for ASD, as well as coding for ELA. They also did not have data describing epidural analgesia drug dosing regimens, or duration of exposure.
Last Updated April 19, 2021
This research was funded in part by the Canadian Institutes of Health Research.
Wall-Wieler’s group reported financial relationships with Aetion, Inc., Alosa Foundation, Lilly, GlaxoSmithKline, Pacira, and Takeda.
Hanley and colleagues reported no relevant relationships with industry.