Early childhood exposure to general anesthesia and subsequent risk of learning disabilities: a systematic review and meta-analysis of cohort studies.

Abstract

Background: Potential neurodevelopmental consequences of early childhood exposure to general anesthesia (GA) remain uncertain, with existing studies reporting inconsistent findings regarding later learning disabilities (LDs). This meta-analysis assessed whether early childhood exposure to general anesthesia is associated with subsequent LDs and whether risks differ by exposure frequency, duration, or LD subtype.

Methods: PubMed, Embase, Ovid, CINAHL, Web of Science, and the Cochrane Library were searched from inception to September 1, 2024. Cohort studies reporting LD outcomes after early childhood GA exposure were included. The primary meta-analysis was restricted to independent cohorts to avoid double-counting participants, whereas overlapping cohorts and studies reporting non-clinical educational outcomes were analyzed separately in sensitivity or secondary analyses. Random-effects models were used to pool risk ratios (RRs), study quality was assessed using the Newcastle-Ottawa Scale, and certainty of evidence was evaluated using GRADE.

Results: Seven cohort studies comprising 167,848 children were analyzed. The primary meta-analysis, restricted to three independent cohorts reporting clinically diagnosed learning disabilities (LDs), showed that early childhood exposure to general anesthesia (GA) was associated with an increased risk of subsequent LDs (RR = 1.23, 95% CI: 1.06-1.43). Exploratory subgroup analyses showed no significant association following a single GA exposure (RR = 1.02, 95% CI: 0.89-1.16), whereas multiple GA exposures were associated with a significantly increased risk of LDs (RR = 2.29, 95% CI: 1.72-3.05). Similarly, no increased risk was observed for GA durations shorter than 60 min, whereas exposures longer than 60 min were associated with progressively higher risk estimates. The certainty of evidence ranged from very low to moderate, with low-certainty evidence for the primary outcome.

Conclusion: Low-certainty evidence suggests that early childhood exposure to GA is associated with an increased risk of subsequent LDs, with larger pooled effect estimates observed following repeated or prolonged exposures. These findings should be interpreted cautiously because residual confounding related to underlying disease, surgical complexity, and hospitalization cannot be excluded. In addition, all included cohorts comprised children born in 2000 or earlier; therefore, the findings may not fully reflect contemporary pediatric anesthesia practice. Further well-designed prospective studies are required.

Trial registration: PROSPERO, CRD42024603831.