Maternal exposure to epidural anesthesia during labor and delivery was not associated with a diagnosis of autism spectrum disorder (ASD) in their children, according to two large studies from British Columbia and Denmark recently published in JAMA.
In the first, conducted by Gillian E. Hanley, PhD, of Vancouver General Hospital Research Pavilion, Vancouver, Canada, and colleagues, the use of maternal epidural analgesia during labor and delivery did cause a small increase in the risk of ASD in offspring. Due to the possibility of residual confounding, however, the significance of this was lessened, and researchers concluded that their evidence did not provide strong support of any association.
To assess whether an association exists between maternal epidural analgesia during labor and delivery with ASD in offspring, Hanley and colleagues used a large, population-based data set of singleton children born in British Columbia, Canada, from April 1, 2000, through Dec. 31, 2014. All children were followed until a clinical diagnosis of ASD, death, or the end of the study (Dec. 31, 2016).
“This is very complex observational research to conduct, and replication in different datasets and different settings is important. However, we were primarily motivated by some data-related advantages. First, British Columbia has very high quality ASD diagnostic data, as were were able to link with a clinical dataset where children are assessed in a standardized way by clinicians who are specifically trained to diagnose ASD (through the BC Autism Assessment Network). Thus, we had high confidence in our ASD data. We also had high quality data on the use of pain relief in labor and other important intrapartum and perinatal care. Thus, we could account for many ways in which the group of women who use epidurals during labor and delivery are different from the group of women who do not. Finally, our data are population-based and date back to 2000, so we could take advantage of mothers who delivered more than one child during our study period to examine whether a mother was more likely to have used an epidural during a labor and delivery when her child was diagnosed with ASD, compared to when her child was not diagnosed with ASD. This controls for other important factors that are likely to remain constant within a woman over time (e.g., genetics, propensity to use medical care, etc). We found no relationship between epidural use and ASD in that analysis,” Hanley told BreakingMED.
Among the 388,254 children included in their current study (mean gestational age: 39.2 weeks; mean follow-up 49.8% female), 1.34% were diagnosed with ASD and 28.7% were exposed to epidural analgesia. Among the 111,480 children exposed to epidural analgesia, 1.53% were diagnosed with ASD compared with 1.26% of those not exposed (absolute risk difference: 0.28%; 95% CI: 0.19%-0.36%), for an unadjusted HR of 1.32 (95% CI: 1.24-1.40) and a fully adjusted HR of 1.09 (95% CI: 1.00-1.15).
Hanley et al concluded that there was no statistically significant association of epidural analgesia use during labor and delivery with ASD upon matched conditional within-woman logistic regression in the exposed group vs the unexposed group (50.6% versus 41.5% (fully adjusted HR: 1.07; 95% CI: 0.87-1.30).
“This is a reassuring finding that suggests a lack of an important association between epidural use during labor and delivery and ASD. Our study provides more evidence that the previously reported association was likely a result of residual confounding (differences between the groups of women who do and do not use epidurals in ways that are themselves related to ASD),” she added.
In another nationwide, retrospective study, Danish researchers led by Anders Pretzmann Mikkelsen, MD, of the Juliane Marie Centre, Copenhagen University Hospital–Rigshospitalet, Copenhagen, Denmark, and colleagues include 479,178 children (median maternal age at delivery: 30.9; 48.7% girls), of whom 19.4% were exposed to epidural analgesia during labor.
After a median follow-up of 7 years, 1.3% of children had received a diagnosis of autism. Children who had been exposed to maternal epidural had an autism diagnosis incidence rate of 23.1 per 10,000 person-years, compared with 8.5 per 10,000 person-years in unexposed children (crude HR: 1.29; 95% CI: 1.21-1.37; adjusted HR: 1.05; 95% CI: 0.98-1.11).
Mikkelson and colleagues did a secondary within-mother analysis in 59,154 children, which showed an estimated autism diagnosis incidence rate of 20.8 per 10,000 person-years in the children exposed to maternal epidural, and 17.1 per 10,000 person-years in those unexposed (adjusted HR: 1.05; 95% CI: 0.90-1.21).
Although the study of a possible association between epidural analgesia during labor and ASD is important, these results have demonstrated that one does not exist, wrote Cynthia A. Wong, MD, and Hanna Stevens, MD, PhD, both of the University of Iowa, in an accompanying editorial.
They noted that two recent studies—one from Qiu et al and the other from Wall-Wieler et al—had conflicting results. Using data from an integrated health system in California, Qiu and colleagues and found an association between epidural analgesia and ASD, while Wall-Wieler, and colleagues found the opposite after analyzing health data from Manitoba, Canada.
“Because of the recent publications, patients and clinicians will legitimately ask whether a risk of ASD should be included in this benefit-risk analysis. Based on these studies and the current knowledge of ASD, it appears that concern for ASD should not carry weight in this decision. Current evidence does not justify considering risk of ASD when deciding whether to use (patients) or recommend (health care professionals) neuraxial labor analgesia,” concluded Wong and Stevens.
Hanley concluded with an eye to future research.
“We are always trying to better understand associations between fetal exposures and ASD, and we do a lot of research in this area. It’s important that we continue to try and understand what is driving the differences in rates of ASD between these groups of women (those who and do not use epidurals during labor and delivery), given that the evidence suggests it is not the epidural itself,” she said.
Limitations of the study from Hanley et al include its observational nature and differences between deliveries. Limitations of the study from Mikkelson et al include reliance on physician-assigned diagnoses, possible misclassification of exposure, the use of a combined outcome, and the possible exposure to other neuraxial analgesia.
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Epidural analgesia during labor was not significantly associated with autism spectrum disorder in children, according to two nationwide studies.
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Results from two large studies should allay fears that epidurals increase risk for autism spectrum disorders in children.
Liz Meszaros, Deputy Managing Editor, BreakingMED™
The study from Hanley and colleagues was funded by an operating grant from the Canadian Institutes of Health Research and was funded by the Sunny Hill Foundation for Children (part of the BC Children’s Hospital Foundation).
Hanley’s work was funded by a new investigator award from the Canadian Institutes of Health Research and a scholar award from the Michael Smith Foundation for Health Research.
The study from Mikkelson et al was funded by The Research Fund of Rigshospitalet, Copenhagen University Hospital.
Mikkelson reported no disclosures.
Cat ID: 41
Topic ID: 83,41,662,730,128,41,135,138,43,192,145,925
