| Objectives:This study aimed to investigate the link between general anesthesia(GA)exposure and neurodevelopmental consequences and investigate the effects of the initial anesthesia exposure time and the number of exposures on subsequent neurodevelopment by meta-analysis.Method:The PubMed,Web of Science,and Cochrane Library databases were searched for investigating neurocognitive outcomes after GA exposure in infants in the past 15 years.All references were processed in Mendeley Desktop 1.19.8(Elsevier,Amsterdam,Holland),after deduplication,with an independent and systematic screening of the titles and abstracts of the articles,followed by a further review of the full text of the filtered articles.To discover observational studies that satisfied the inclusion and exclusion criteria,the same approach was utilized for two rounds of screening.The papers’ outcome data,including relative risk(RR),hazard ratio(HR),or odds ratio(OR),and 95%confidence interval(CIs),were retrieved.To calculate and compare the following neurodevelopmental outcomes of children with GA to children who were not exposed,HR and OR were translated into RR using a formula.The quality of each observational study was assessed using the Newcastle-Ottawa Scale(NOS).The retrieved data were analyzed with Stata/MP 14.0.By using meta regression,the GA exposure frequency and GA exposure age were examined.The quality of each observational study was assessed using the Newcastle-Ottawa Scale(NOS).This systematic review was registered in PROSPERO(registration number CRD42022333086).Results:After a rigorous search for the keywords of the articles,nine articles on single and multiple anesthesia exposures and neurodevelopmental outcomes were screened by title,abstract,and full text.A total of 146006 children born between 1976 and 2014 were enrolled,of whom 23186 children aged<4 years underwent GA due to surgery.After exposure,the children were followed-up,and neurodevelopmental assessments were done before the age of 19 years.An association of the GA exposure with neurodevelopmental impairment was analyzed as a pooled RR of 1.39(95%CI 1.22-1.58,P<0.001).The pooled RR was 1.16(95%CI 1.05-1.28,P=0.004)and 1.79(95%CI 1.53-2.10,P<0.001)for single and multiple anesthesia exposures,respectively.Meta-regression analysis revealed that the number of exposures was a risk factor for adverse neurodevelopmental outcomes(RR=1.55,95%1.261.91,P<0.001),not the time of exposure before 4 years of age(RR=0.91,95%CI 0.77-2.17,P=0.273).Conclusions:The included studies showed a modestly elevated risk of adverse neurodevelopmental outcomes in children exposed to anesthesia during early childhood.However,there seems to be no causative relationship between the time of exposure to the initial GA and neurodevelopmental impairment. |
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