Association of labor epidural analgesia exposure with long-term risk of autism spectrum disorder in offspring: A meta-analysis of observational studies.

A previous meta-analysis has demonstrated a superior analgesic efficacy of epidural analgesia (e.g. labor epidural analgesia) in comparison with non-epidural approaches. The widely accepted safety of labor epidural analgesia also endorses its current popularity in obstetric practice. However, the results of a recent large-scale longitudinal study that demonstrated a significant increase in risk of autism spectrum disorder in offspring from mothers with labor epidural analgesia exposure have raised some concerns over the safety of its use. The current meta-analysis aimed at examining the strength of evidence regarding this issue based on updated clinical data. Through systematically reviewing seven eligible observational studies involving 4,021,406 children from electronic databases, our results showed a slight but statistically significant increase in risk of autism spectrum disorder in children with exposure to labor epidural analgesia compared with those without. The finding was consistent in subgroup analysis focusing on siblings and children delivered vaginally. Nevertheless, despite the tendency of an increased risk of autism spectrum disorder in children exposed to labor epidural analgesia <4 h, this effect was not observed in those exposed to labor epidural analgesia >8 h (data from two studies). In conclusion, the level of evidence linking labor epidural analgesia to autism spectrum disorder development in offspring was very low based on the latest data because of the small effect size and the finding of a lack of cumulative dose-response effect in the current analysis. Further studies are warranted to provide an insight into this issue.