Early exposure to general anesthesia may contribute to later attention-deficit/hyperactivity disorder (ADHD): A systematic review and meta-analysis of cohort studies

Study objective

The association between early childhood exposure to general anesthesia and subsequent risk of developing attention-deficit/hyperactivity disorder remains unknown.

Design

A systematic review and meta-analysis of cohort studies.

Patients

Children undergoing general anesthesia.

Interventions

A comparison of any type of general anesthesia exposure, including total intravenous anesthesia, inhalation general anesthesia, and combined intravenous and inhaled anesthesia, with non-anesthetic exposures, which did not receive any exposure to anesthetic drugs, including general anesthetics as well as local anesthetics.

Measurements

The primary outcome measure was the risk of developing attention-deficit/hyperactivity disorder after general anesthesia exposure.

Main results

The results of the overall meta-analysis showed an increased risk of subsequent attention-deficit/hyperactivity disorder in children exposed to general anesthesia (RR = 1.26, 95% CI, 1.16–1.38; P < 0.001; I² = 44.6%). Subgroup analysis found that a single exposure to general anesthesia in childhood was associated with an increased risk of developing attention-deficit/hyperactivity disorder (RR = 1.29, 95% CI, 1.19–1.40, P < 0.001; I² = 2.6%), and the risk of attention-deficit/hyperactivity disorder was further increased after multiple general anesthesia exposures (RR = 1.61, 95% CI, 1.32–1.97, P < 0.001; I² = 57.6%). Exposure to general anesthesia lasting 1–60 min during childhood is associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) (RR: 1.38, 95% CI: 1.26–1.51, P < 0.001; I² = 0.0%). Moreover, with longer durations of exposure (61–120 min), the risk further rises (RR: 1.55, 95% CI: 1.21–1.99, P = 0.001; I² = 37.8%). However, no additional increase in ADHD risk was observed with exposures exceeding 120 min (RR: 1.55, 95% CI: 1.35–1.79, P < 0.001; I² = 0.0%).

Conclusions

Exposure to general anesthesia during early childhood increases the risk of developing attention-deficit/hyperactivity disorder. In particular, multiple general anesthesia exposures and exposures longer than 60 min significantly increase the risk of developing ADHD.