Maternal exposure to labor epidural analgesia (LEA) may be associated with an increased risk of autism spectrum disorders (ASDs) in offspring, according to the findings of a recently published retrospective population-based study.

As evidence surrounding the long-term health effects of maternal use of LEA in offspring is limited, this longitudinal birth cohort study aimed to determine the association between maternal LEA exposure and ASD risk in children. A single integrated health care system was utilized to obtain electronic medical records of 147,895 singleton children who were delivered vaginally between January 1, 2008, and December 31, 2015.

“Children were followed up from the age of 1 year until the first date of the following occurrences: clinical diagnosis of ASD, last date of health plan enrollment, death, or the study end date of December 31, 2018,” the authors explained. A clinical diagnosis of ASD was the main outcome of the study.

Of the total children included in the study, 109,719 (74.2%) were exposed to maternal LEA while 38,176 were not. The study authors reported that 11.9% (n=13,055) of mothers in the LEA group experienced fever during labor compared with 1.3% (n=510) of mothers in the non-LEA group. Additionally, data analysis revealed that ASDs were diagnosed in 1.9% (n=2039) of children in the LEA group compared with 1.3% (n=485) of children in the non-LEA group.

The study authors reported that, after adjusting for potential confounders, the hazard ratio (HR) associated with exposure to LEA vs no exposure was calculated to be 1.37 (95% CI, 1.23-1.53). “Relative to the unexposed group, the adjusted HR associated with LEA exposure of less than 4 hours was 1.33 (95% CI, 1.17-1.53), with LEA exposure of 4 to 8 hours was 1.35 (95% CI, 1.20-1.53), and with LEA exposure of more than 8 hours was 1.46 (95% CI, 1.27-1.69),” they added.

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Findings of the study also showed that, after adjusting for covariates, a “significant trend” was observed between ASD risk and increased duration of LEA exposure within the LEA group (HR for linear trend, 1.05 per 4 hours; 95% CI, 1.01-1.09). The authors noted that the HR estimate associated with LEA exposure did not change when fever was added to the model (adjusted HR for LEA vs non-LEA, 1.37; 95% CI, 1.22-1.53).

“Our findings raise the concern that the short duration of LEA exposure may be associated with long-term neurodevelopmental disorders in offspring,” the study authors concluded. This risk, however, does not appear to be associated with epidural-related maternal fever. The authors added, “We believe that further research is warranted to confirm our study findings and to investigate the probable mechanistic association between LEA and ASD.”


Qui C, Lin JC, Shi JM, et al. Association between epidural analgesia during labor and risk of autism spectrum disorders in offspring. JAMA Pediatr. 2020. doi: 10.1001/jamapediatrics.2020.3231.