Labour epidural analgesia may be associated with an increased autism spectrum disorder risk

1. In a population-based study based in Southern California, the risk of autism spectrum disorder (ASD) in children was increased with exposure to labour epidural analgesia (LEA), independent of exposure to oxytocin.

2. There was no significant association between risk of ASD and exposure to oxytocin in labour, independently of exposure to LEA.

Evidence Rating Level: 2 (Good)

While some population-based studies have reported an association between labour epidural analgesia (LEA) and risk of children with autism spectrum disorder (ASD), the results overall from these studies have been inconsistent. Furthermore, numerous drugs are often used at or around the time of labour, such as oxytocin, which may confound this potential association. Therefore, this current population-based study based in Southern California aimed to assess the independent and synergistic relationship between LEA and oxytocin, and the risk of ASD. The cohort was drawn from singleton pregnancies delivered vaginally between 28 and 44 weeks, from 2008 to 2017, with diagnoses of ASD included if made before 2021. In total, there were 205,994 enrolled, 74.7% with LEA during their delivery and 57.2% with oxytocin. Exposure to oxytocin was greater for those with LEA (67.7%) than those without (26.1%). 2.5% of children had a diagnosis of ASD. 2.7% of these were in the LEA group and 1.9% were in the non-LEA group. The hazard ratios for ASD risk were 1.41 (95% CI 1.31-1.51) for LEA exposed versus non-exposed, and 1.25 (95% CI 1.18-1.32) for oxytocin exposed versus non-exposed. After adjusting for sociodemographic factors, antenatal and labour risk factors, and birth defects, the HRs were 1.30 (95% CI 1.20-1.39) and 1.11 (95% CI 1.05-1.18) respectively. When adjusting for oxytocin exposure, the ASD risk for LEA-exposed children was still significant (HR 1.28, 95% CI 1.18-1.38), though when adjusting for LEA exposure, the ASD risk for oxytocin-exposed children was no longer significant (HR 1.05, 95% CI 0.99-1.12). There was also a significant interaction between LEA and oxytocin exposures (p = 0.02). In conclusion, this study demonstrated an association between LEA exposure in vaginal delivery and risk of ASD in offspring, independent of oxytocin exposure, but no significant association between oxytocin exposure and ASD independent of LEA exposure. 

Click to read the study in JAMA Network Open

Image: PD

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