[Skip to Navigation]
Original Investigation
April 19, 2021

Association of Epidural Labor Analgesia With Offspring Risk of Autism Spectrum Disorders

Author Affiliations
  • 1Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
  • 2Manitoba Centre for Health Policy, University of Manitoba, Winnipeg, Manitoba, Canada
  • 3Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Boston, Massachusetts
  • 4Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
  • 5Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Stanford, California
JAMA Pediatr. 2021;175(7):698-705. doi:10.1001/jamapediatrics.2021.0376
Key Points

Question  Is epidural labor analgesia (ELA) associated with increased offspring risk of autism spectrum disorder (ASD)?

Findings  In this cohort study of 123 175 offspring born in Manitoba, Canada, from 2005 to 2016, after accounting for maternal sociodemographic, preexisting, pregnancy-related, and birth-specific factors, no association was found between ELA exposure and offspring risk of ASD.

Meaning  Results of this study suggest that ELA is not associated with an increased risk of ASD in offspring.


Importance  Epidural labor analgesia (ELA) has been associated with an increased offspring risk of autism spectrum disorder (ASD). Whether this finding may be explained by residual confounding remains unclear.

Objective  To assess the association between ELA and offspring risk of ASD.

Design, Setting, and Participants  Longitudinal cohort study of vaginal deliveries of singleton live infants born from 2005 to 2016 from a population-based data set linking information from health care databases in Manitoba, Canada; offspring were followed from birth until 2019 or censored by death or emigration. Data were analyzed from October 19, 2020, to January 22, 2021.

Exposures  Epidural labor analgesia.

Main Outcomes and Measures  At least 1 inpatient or outpatient diagnosis of ASD in offspring aged at least 18 months. For the full population and a sibling cohort, inverse probability of treatment-weighted Cox proportional hazards regression analyses were used to control for potential confounders.

Results  Of the 123 175 offspring included in this study (62 647 boys [50.9%]; mean [SD] age of mothers, 28.2 [5.8] years), 47 011 (38.2%) were exposed to ELA; 2.1% (985 of 47 011) of exposed vs 1.7% (1272 of 76 164) of unexposed offspring were diagnosed with ASD in the follow-up period (hazard ratio [HR], 1.25; 95% CI, 1.15-1.36). After adjusting for maternal sociodemographic, prepregnancy, pregnancy, and perinatal covariates, ELA was not associated with an offspring risk of ASD (inverse probability of treatment–weighted HR, 1.08; 95% CI, 0.97-1.20). In the within-siblings design adjusting for baseline covariates, ELA was not associated with ASD (inverse probability of treatment–weighted HR, 0.97; 95% CI, 0.78-1.22). Results from sensitivity analyses restricted to women without missing data who delivered at or after 37 weeks of gestation, firstborn infants only, and offspring with ASD classified with at least 2 diagnostic codes were consistent with findings from the main analyses.

Conclusions and Relevance  In a Canadian population-based birth cohort study, no association between ELA exposure and an increased offspring risk of ASD was found.

Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    1 Comment for this article
    Misleading Title
    Magdy Gad, MD | PIMC
    The study title should have been "NO" Association which is what that cohort study has concluded!! With such very sensitive subject and many unknown, there is much more harm such a title could do by falsely discouraging women from getting epidural when it would have several benefits both for the mother and the newborn as well documented form many studies. This is reminiscent of the MMR vaccine claim and what "Bad" effects it caused.
    CONFLICT OF INTEREST: I do epidurals for labor pain and my wife had them for all my 3 children!!