title: Risk of autistic disorder after exposure to general anaesthesia and surgery: a nationwide, retrospective matched cohort study.
abstract: BACKGROUND
  Deficits of learning, memory and cognition have been observed in newborn animals exposed to general anaesthetics. However, conclusions from clinical studies conducted in humans to investigate the relationship between anaesthesia and neurodevelopmental disorders have been inconsistent. Autistic disorder is typically recognised earlier than other neurobehavioural disorders. Although certain genes apparently contribute to autistic disorder susceptibility, other factors such as perinatal insults and exposure to neurotoxic agents may play a crucial role in gene-environmental interaction.
  
  
  OBJECTIVE
  This study was designed to investigate the association of exposure to general anaesthesia/surgery with autistic disorder. We hypothesised that exposure to general anaesthesia and surgery before 2 years of age is associated with an increased risk of developing autistic disorder.
  
  
  METHODS
  A retrospective matched-cohort study.
  
  
  METHODS
  A medical university. Data from the National Health Insurance Research Database of Taiwan from 2001 to 2010 were analysed.
  
  
  METHODS
  The birth cohort included 114,435 children, among whom 5197 were exposed to general anaesthesia and surgery before the age of 2 years. The 1 : 4 matched controls comprised 20,788 children.
  
  
  METHODS
  The primary endpoint was the diagnosis of autistic disorder after the first exposure to general anaesthesia and surgery.
  
  
  RESULTS
  No differences were found in the incidence of autistic disorder between the exposed group (0.96%) and the unexposed controls (0.89%) (P = 0.62). Cox proportional regression showed that the hazard ratio of exposure to general anaesthesia and surgery was 0.93 [95% confidence interval (95% CI) 0.57 to 1.53] after adjusting for potential confounders. Age at first exposure did not influence the risk of autistic disorder. No relationship was found between the total number of exposures and the risk of autistic disorder.
  
  
  CONCLUSIONS
  Exposure to general anaesthesia and surgery before the age of 2 years age at first exposure and number of exposures were not associated with the development of autistic disorder.
authors.affiliation: From the Institute of Medicine, Chung Shan Medical University (W-RK, L-YL), Department of Anaesthesiology, Chung Shan Medical University and Hospital (W-RK), Department of Public Health and Institute of Public Health, Chung Shan Medical University (J-YH, Y-CC, ONN, P-CK, S-RJ, C-CL, Y-PL), Department of Family and Community Medicine, Chung Shan Medical University Hospital (Y-CC, C-CL, Y-PL), Department of Public Health (H-CC), EBM Centre & Library (H-CC), College of Medicine, Chung Shan Medical University (L-YL), Department of Obstetrics and Gynaecology, Chung Shan Medical University Hospital, Taichung, Taiwan (L-YL).
authors.forename: Wen-Ru
authors.initials: WR
authors.lastname: Ko
authors.forename: Jing-Yang
authors.initials: JY
authors.lastname: Huang
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Chiang
authors.forename: Oswald Ndi
authors.initials: ON
authors.lastname: Nfor
authors.forename: Pei-Chieh
authors.initials: PC
authors.lastname: Ko
authors.forename: Shiou-Rung
authors.initials: SR
authors.lastname: Jan
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Lung
authors.forename: Hui-Chin
authors.initials: HC
authors.lastname: Chang
authors.forename: Long-Yau
authors.initials: LY
authors.lastname: Lin
authors.forename: Yung-Po
authors.initials: YP
authors.lastname: Liaw
mesh_terms: D000768:Anesthesia, General / Q000009:adverse effects / Q000639:trends*; D018681:Anesthetics, General / Q000009:adverse effects; D001321:Autistic Disorder / Q000175:diagnosis / Q000453:epidemiology*; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D011183:Postoperative Complications / Q000175:diagnosis / Q000453:epidemiology*; D012189:Retrospective Studies; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
chemical_list: D018681:Anesthetics, General