title: Association between childhood exposure to single general anesthesia and neurodevelopment: a systematic review and meta-analysis of cohort study.
abstract: OBJECTIVE
  Many studies have been done to seek the relationship between general anesthesia and neurodevelopment in pediatrics. However, there is no unified conclusion, especially single anesthesia affecting a child before 3 and 4 years. The association between anesthesia and neurodevelopment is studied using a meta-analysis.
  
  
  METHODS
  We summarized the currently available evidence by searching PubMed, EMBASE, and the Cochrane library over the past 10 years. An evaluation of neurodevelopment including learning disability, behavioral disorders, and cognitive problems was conducted. We estimated the synthesized hazard ratios (HR) and 95 % confidence interval (CI) according to inter-study heterogeneity and analyzed the factors for this association using meta-regression method.
  
  
  RESULTS
  Thirteen eligible studies met the inclusion criteria. The neurodevelopment damage was associated with single general anesthesia before age of 4 (adjusted HR 1.28 95 % CI 1.10-1.45). The pooled adjusted HR was 1.17 (95 % CI 1.07-1.28, p = 0.001) before 4 years old after the influence analysis and the adjusted HR was 1.18 (95 % CI 1.07-1.30, p = 0.001) before 3 years old. There was no significant difference between 3 and 4 years exposed to single general anesthesia (HR3/HR4 = 1.008, p = 0.9). Due to limitations of retrospective studies, prospective investigations are needed to determine whether anesthesia is causative.
  
  
  CONCLUSIONS
  The current evidence suggests a modestly elevated risk of neurodevelopmental disorders exists in children near 3 years of age. A single general anesthesia is relatively safe after 3 years, as the outcome is very close before 3 and 4 years old.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhizaoju Road, Huangpu District, Shanghai, 200011, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhizaoju Road, Huangpu District, Shanghai, 200011, China.
authors.forename: Zijing
authors.initials: Z
authors.lastname: Du
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhizaoju Road, Huangpu District, Shanghai, 200011, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhizaoju Road, Huangpu District, Shanghai, 200011, China. handong12000@163.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhizaoju Road, Huangpu District, Shanghai, 200011, China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Li
mesh_terms: D000768:Anesthesia, General / Q000009:adverse effects*; D002675:Child, Preschool; D015331:Cohort Studies; D006801:Humans; D065886:Neurodevelopmental Disorders / Q000209:etiology*; D012306:Risk
keywords: Anesthesia, general anesthetics; Cohort studies; Infant; Neurodevelopmental; Newborn; Pediatrics