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

Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusions: 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.