Abstract
BackgroundSeveral epidemiological studies have been conducted to address the later effect of anesthesia on neurodevelopment in children. However, the results are still inconclusive.MethodsWe here conducted a systematic review and meta-analysis to summarize the currently available clinical and epidemiologic evidence on the association of anesthesia/surgery with neurodevelopmental outcomes in children by searching PubMed, EMBASE, and Web of Science database (from January-1 2000 to February-1, 2013). The evaluation of neurodevelopment includes language and learning disabilities, cognition, behavioral development, and academic performance. Both retrospective and prospective studies were included. Data were abstracted from seven eligible studies. We estimated the synthesized hazard ratios (HR) and 95% confidence interval (CI) according to inter-study heterogeneity.ResultsThe pooled HR for the association of anesthesia/surgery with an adverse behavioral or developmental outcome was 1.25 (95% CI, 1.13–1.38, P<0.001; random-effects model) in children undergoing the first anesthesia before the age of 4-year. Then we analyzed the factors for this association using meta-regression method. It showed that it was the number of times of exposure (HR = 1.75, 95% CI 1.31–2.33; P<0.001) rather than the time at exposure before 4-year (HR = 1.08, 95% CI 0.87–1.34 for the effect of per 1-year early exposure; P = 0.47) is a risk factor for neurodevelopmental impairment.ConclusionThe current clinical evidence suggests modestly elevated risk of adverse neurodevelopmental outcomes in children who were exposed to anesthesia/surgery during early childhood, especially for those with multiple times of exposure. Due to limitation of retrospective studies, prospective investigations are needed to determine whether anesthesia/surgery is causative.
Highlights
Anesthesia in children is safe within short-term observation and has enabled children worldwide to undergo surgical procedure according to currently available clinical measurements, researchers are paying close attention to the question whether an administration of general anesthetic would lead to later neurodevelopmental deficits in children
DiMaggio et al have performed a Bayesian meta-analysis to investigate the association between pediatric anesthesia and neurodevelopmental impairment
The minimum age at exposure was at birth to six months and the maximum age was at the age of four years, with a mean age of three years
Summary
Anesthesia in children is safe within short-term observation and has enabled children worldwide to undergo surgical procedure according to currently available clinical measurements, researchers are paying close attention to the question whether an administration of general anesthetic would lead to later neurodevelopmental (cognitive and behavioral) deficits in children.An increasing volume of experimental and laboratory researches over the past decade have established a relationship between the administration of general anesthetics during periods of rapid brain growth and an increase in neuronal apoptosis and subsequent long-term neurodevelopmental impairment either in rodents or in nonhuman primates. [1,2,3] These results had raised the increasing concerns in clinicians and medical policy makers. Anesthesia in children is safe within short-term observation and has enabled children worldwide to undergo surgical procedure according to currently available clinical measurements, researchers are paying close attention to the question whether an administration of general anesthetic would lead to later neurodevelopmental (cognitive and behavioral) deficits in children. [4] The synthesized hazard ratios (HRs) based on seven unadjusted and six adjusted measures for the association of anesthesia/surgery with an adverse developmental outcome were 1.9 (95% confidence interval [CI], 1.2–3.0) and 1.4 (95% CI, 0.9–2.2), respectively. They failed to include all eligible studies available at the time of analysis, e.g., the study by Hansen et al [5].
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