Current clinical evidence on the effect of general anesthesia on neurodevelopment in children: an updated systematic review with meta-regression.
BACKGROUND
Several epidemiological studies have been conducted to address the later effect of anesthesia on neurodevelopment in children. However, the results are still inconclusive.


METHODS
We 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.


RESULTS
The 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.


CONCLUSIONS
The 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.
Department of Anesthesiology, Shanghai Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, P.R. China.
Xin
X
Wang
Department of Anesthesiology, Shanghai Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, P.R. China.
Zheng
Z
Xu
Department of Anesthesiology, Shanghai Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, P.R. China.
Chang-Hong
CH
Miao
D000768:Anesthesia, General / Q000009:adverse effects*; D018681:Anesthetics, General / Q000008:administration & dosage / Q000009:adverse effects*; D001921:Brain / Q000187:drug effects*; D002648:Child; D002657:Child Development / Q000187:drug effects*; D006801:Humans; D007802:Language; D007859:Learning Disabilities / Q000139:chemically induced*; D012307:Risk Factors
D018681:Anesthetics, General