Anesthetic Exposure During Childhood and Neurodevelopmental Outcomes: A Systematic Review and Meta-analysis

IMPORTANCE: Clinical studies of neurodevelopmental outcomes after anesthetic exposure have evaluated a range of outcomes with mixed results. OBJECTIVE: To examine via meta-analyses the associations between exposure to general anesthesia and domain-specific neurodevelopmental outcomes in children. DATA SOURCES: PubMed/MEDLINE, Embase, CINAHL, Web of Science and the Cochrane Library were searched from inception to August 31, 2021. STUDY SELECTION: Inclusion criteria were exposures to procedures requiring general anesthesia at younger than 18 years and evaluation of long-term neurodevelopmental function after exposure. Studies lacking unexposed controls or focused on children with major underlying comorbidities were excluded. DATA EXTRACTION AND SYNTHESIS: Extracted variables included effect size; hazard, risk, or odds ratio; number of exposures; procedure type; major comorbidities; age of exposure and assessment; presence of unexposed controls; and study design. Studies were independently reviewed by 2 coders, and review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES: The main outcomes were standardized mean differences (SMD) for scores in the neurodevelopmental domains of academics, behavioral problems, cognition, executive function, general development, language, motor function, nonverbal reasoning, social cognition, and hazard and risk of neurodevelopmental disorder diagnoses. RESULTS: A total of 31 studies contributed data for meta-analysis. For each of the assessed neurodevelopmental domains, the numbers of children evaluated ranged from 571 to 63 315 exposed and 802 to 311 610 unexposed. Children with any exposure (single or multiple) had significantly worse behavioral problems scores, indicating more behavioral problems (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). Higher incidences of neurodevelopmental disorder diagnoses were also reported (hazard ratio, 1.19; 95% CI, 1.09 to 1.30; P < .001; risk ratio, 1.81; 95% CI, 1.25 to 2.61; P = .002). CONCLUSIONS AND RELEVANCE: These findings support the hypothesis that associations between anesthetic exposure during childhood and subsequent neurodevelopmental deficits differ based on neurodevelopmental domain.