Association Between Epidural Labor Analgesia and Autism Spectrum Disorder in Offspring: A Systematic Review and Meta-Analysis

Abstract

Purpose

Many studies have focused on the association between Autism spectrum disorder (ASD) and epidural labor analgesia (ELA), which is the most effective way to manage labor pain. The purpose of this meta-analysis was to summarize the current state of the association between ELA and ASD.

Methods

A search of the literature yielded 201 relevant studies, of which 7 cohort studies met our inclusion criteria. Two independent reviewers screened the inclusion results, extracted data, and assessed the risk of bias and quality of evidence.

Results

Compared to parturient who did not receive ELA, parturient who received ELA had a slightly increased risk of ASD (adjusted hazard ratio [aHR], 1.12; 95% confidence interval [CI], 1.06–1.17; I2, 69%; P < 0.001; seven studies). After excluding one literature (aHR, 1.09; 95% CI, 1.06–1.12; I2, 4%; P < 0.001; six studies). The sensitivity analyses had consistent outcomes with the main analyses involving siblings (aHR 1.11; 95% CI 1.03–1.19), cesarean section and instrumental deliveries (aHR 1.07; 95% CI 1.03–1.10), non-overlapping populations (aHR 1.09; 95% CI 1.05–1.12), full-term birth populations (aHR 1.10; 95% CI 1.06–1.14), and studies assessed to have moderate risk of bias (aHR 1.09; 95% CI 1.02–1.16).

Conclusion

This meta-analysis revealed a modest positive association between ELA and ASD, acknowledging a slight potential risk. However, it is important to note that this risk cannot be completely dismissed due to the possibility of bias and this association is based on low-quality evidence. Future studies are required to assess and mitigate different confounding biases and investigate the time-dose-response relationship.

Keywords:

• Autism spectrum disorder
• epidural analgesia
• epidural labor analgesia
• ELA
• neuraxial labor analgesia
• pregnancy
• meta-analysis

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by National Natural Science Foundation of China (grant no. 81772131).