This systematic review and meta-analysis examined nineteen observational studies to assess the relationship between neuraxial labour analgesia and neurodevelopmental disorders in offspring. The exposure included epidural, caudal, or combined spinal-epidural anaesthesia during labour. The primary outcomes focused on autism spectrum disorder, attention-deficit/hyperactivity disorder, and other neurodevelopmental conditions.
The analysis revealed mixed results depending on the study design. In sibling-matched cohorts, the data indicated no association between the exposure and autism spectrum disorder or attention-deficit/hyperactivity disorder. However, population-based analyses reported a small increase in risk for autism spectrum disorder after adjustment. Other neurodevelopmental outcomes showed no clinically meaningful associations.
The authors highlight significant limitations inherent to the reliance on observational evidence, which is susceptible to residual confounding. They note that effect estimates attenuated with increasing control for familial confounding. Consequently, no convincing evidence of a causal association was found. The certainty of the evidence remains limited by the study designs included in the review.
Clinicians should interpret these findings with caution, recognizing that association does not imply causation. The review suggests that current observational data do not support a causal link between neuraxial labour analgesia and adverse neurodevelopmental outcomes in children.
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BACKGROUND: Whether neuraxial analgesia during labour influences offspring neurodevelopment remains controversial, largely because of reliance on observational evidence susceptible to residual confounding. We aimed to re-evaluate this association through an updated and methodologically rigorous systematic review and meta-analysis, with particular emphasis on family-based designs that better account for shared familial factors.
METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched to September 16, 2025. Eligible studies assessed epidural, caudal, or combined spinal-epidural anaesthesia during labour and reported clinically defined neurodevelopmental outcomes. Random-effects meta-analyses with restricted maximum likelihood estimation were performed, with prespecified sibling-matched analyses.
RESULTS: Nineteen studies were included. In sibling-matched cohorts, which provide stronger control for shared genetic and familial confounding, neuraxial labour analgesia was not associated with autism spectrum disorder (ASD) (adjusted hazard ratio 1.06; 95% confidence interval 0.98-1.14) or attention-deficit/hyperactivity disorder. Population-based analyses showed a small increase in ASD risk after adjustment (adjusted hazard ratio 1.10; 95% confidence interval 1.08-1.13), but effect estimates attenuated with increasing control for familial confounding. No clinically meaningful associations were observed for other neurodevelopmental outcomes.
CONCLUSIONS: Across population-based and family-based observational evidence, this updated systematic review and meta-analysis showed that there is no convincing evidence that neuraxial labour analgesia is associated with an increased risk of ASD, attention-deficit/hyperactivity disorder or other neurodevelopmental disorders in offspring.
SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD420251148665).