Long-term neurodevelopmental and psychiatric risks after general anesthesia in early childhood: a nationwide...

Pre-clinical evidence suggests that general anesthesia (GA) may have neurotoxic effects on the developing brain, but clinical findings remain inconsistent. Most studies have had limited follow-up or focused on selected neurodevelopmental outcomes, and residual confounding related to surgery remains difficult to address. We investigated the association between GA exposure before age 3 and a broad spectrum of neurodevelopmental disorders (NDDs) diagnosed through adolescence.

Using the South Korean National Health Insurance Service database, we identified 1,116,195 children born between 2005 and 2007. We compared children exposed to GA before age 3 with unexposed controls. The primary outcome was a new NDD diagnosis from the third birthday through 2023. Statistical analyses included 1:5 propensity-score matching with stratified Cox proportional hazards regression and multivariable Cox regression incorporating Total Relative Value Units (TRVUs) as an administrative proxy for surgical complexity.

In the matched cohort (n = 131,699), GA exposure was associated with a higher risk of NDDs (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.12-1.26). The largest HRs were observed for intellectual disability (HR, 1.56; 95% CI, 1.32-1.85) and autism spectrum disorder (HR, 1.46; 95% CI, 1.17-1.82).

Exposure to GA before age 3 was associated with a modestly higher risk of NDDs diagnosed through adolescence. Exploratory findings according to anesthetic and surgical burden should be interpreted cautiously because unmeasured confounding cannot be excluded.