General Anesthesia Exposure in Childhood Tied to Neurodevelopmental Deficits

In a systematic review and meta-analysis, researchers assessed whether exposure to general anesthesia during childhood was associated with deficits in specific neurodevelopmental domains.

Associations were found between pediatric patients exposed to general anesthesia and future neurodevelopmental deficits that vary by neurodevelopmental domain in systematic review and meta-analysis published in the JAMA Network Open.

Previous studies examining the association between neurodevelopmental outcomes following exposure to anesthesia have left unclear results. With millions of children exposed to anesthesia annually, researchers sought to map neurodevelopmental outcomes following anesthesia exposure into neurodevelopmental domains and analyze if that exposure is associated with deficits in specific domains.

They conducted a systematic review and meta-analysis that included 31 studies from PubMed/MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane Library from their launch through August 31, 2021 of children less than 18 years of age requiring general anesthesia and subsequent assessment of long-term neurodevelopmental function. Exclusions included studies of children with significant comorbidities and those lacking unexposed-to-anesthesia control individuals. The primary outcomes were standardized mean differences (SMD) in multiple neurodevelopmental domains.

Among the neurodevelopmental domains examined, there were between 571 and 63,315 children exposed to anesthesia and between 802 and 311,610 children not exposed. Those exposed showed significantly worse behavioral problems scores (SMD, −0.10; 95% CI, −0.18 to −0.02; P =.02), and worse scores in academics (SMD, −0.07; 95% CI, −0.12 to −0.01; P =.02), cognition (SMD, −0.03; 95% CI, −0.05 to 0.00; P =.03), executive function (SMD, −0.20; 95% CI, −0.32 to −0.09; P <.001), general development (SMD, −0.08; 95% CI, −0.13 to −0.02; P =.01), language (SMD, −0.08; 95% CI, −0.14 to −0.02; P =.01), motor function (SMD, −0.11; 95% CI, −0.21 to −0.02; P =.02), and nonverbal reasoning (SMD, −0.15; 95% CI, −0.27 to −0.02; P =.02).

The researchers also noted a higher incidence of a neurodevelopmental disorder diagnosis among pediatric patients exposed to anesthesia with a hazard ratio of 1.19 (95% CI, 1.09-1.30; P <.001) and risk ratio of 1.81 (95% CI, 1.25-2.61; P =.002).

Study limitations included between-study heterogeneity, unmeasured confounding, scores in some domains inherently related to scores in other domains, and no P value adjustment for multiple comparisons.

Researchers stated that deficit patterns were found in specific domains, “with comparatively larger effect sizes seen in the executive function, nonverbal reasoning, motor function, and behavioral problems, particularly externalizing behavioral problems, domains, coupled with an increased incidence of neurodevelopmental disorder diagnoses, particularly ADHD diagnosis.”

They added that “potential phenotypes of neurodevelopmental deficit that are associated with general anesthesia exposure have been identified.”

Further research is warranted to determine causality exists.


Reighard C, Junaid S, Jackson WM, et al. Anesthetic exposure during childhood and neurodevelopmental outcomes: A systematic review and meta-analysis. JAMA Netw Open. June 1, 2022;5(6):e2217427. doi:10.1001/jamanetworkopen.2022.17427