title: Cognitive and behavioral outcomes after early exposure to anesthesia and surgery.
abstract: BACKGROUND
  Annually, millions of children are exposed to anesthetic agents that cause apoptotic neurodegeneration in immature animals. To explore the possible significance of these findings in children, we investigated the association between exposure to anesthesia and subsequent (1) learning disabilities (LDs), (2) receipt of an individualized education program for an emotional/behavior disorder (IEP-EBD), and (3) scores of group-administered achievement tests.
  
  
  METHODS
  This was a matched cohort study in which children (N = 8548) born between January 1, 1976, and December 31, 1982, in Rochester, Minnesota, were the source of cases and controls. Those exposed to anesthesia (n = 350) before the age of 2 were matched to unexposed controls (n = 700) on the basis of known risk factors for LDs. Multivariable analysis adjusted for the burden of illness, and outcomes including LDs, receipt of an IEP-EBD, and the results of group-administered tests of cognition and achievement were outcomes.
  
  
  RESULTS
  Exposure to multiple, but not single, anesthetic/surgery significantly increased the risk of developing LDs (hazard ratio: 2.12 [95% confidence interval: 1.26-3.54]), even when accounting for health status. A similar pattern was observed for decrements in group-administered tests of achievement and cognition. However, exposure did not affect the rate of children receiving an individualized education program.
  
  
  CONCLUSIONS
  Repeated exposure to anesthesia and surgery before the age of 2 was a significant independent risk factor for the later development of LDs but not the need for educational interventions related to emotion/behavior. We cannot exclude the possibility that multiple exposures to anesthesia/surgery at an early age may adversely affect human neurodevelopment with lasting consequence.
authors.affiliation: Department of Anesthesiology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA. flick.randall@mayo.edu
authors.forename: Randall P
authors.initials: RP
authors.lastname: Flick
authors.forename: Slavica K
authors.initials: SK
authors.lastname: Katusic
authors.forename: Robert C
authors.initials: RC
authors.lastname: Colligan
authors.forename: Robert T
authors.initials: RT
authors.lastname: Wilder
authors.forename: Robert G
authors.initials: RG
authors.lastname: Voigt
authors.forename: Michael D
authors.initials: MD
authors.lastname: Olson
authors.forename: Juraj
authors.initials: J
authors.lastname: Sprung
authors.forename: Amy L
authors.initials: AL
authors.lastname: Weaver
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Schroeder
authors.forename: David O
authors.initials: DO
authors.lastname: Warner
mesh_terms: D017677:Age Distribution; D017668:Age of Onset; D000758:Anesthesia / Q000009:adverse effects* / Q000379:methods; D016022:Case-Control Studies; D002648:Child; D002653:Child Behavior Disorders / Q000453:epidemiology / Q000209:etiology*; D002675:Child, Preschool; D003072:Cognition Disorders / Q000453:epidemiology / Q000209:etiology*; D016001:Confidence Intervals; D002658:Developmental Disabilities / Q000453:epidemiology / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007859:Learning Disabilities / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D016016:Proportional Hazards Models; D012016:Reference Values; D012189:Retrospective Studies; D018570:Risk Assessment; D017678:Sex Distribution; D013514:Surgical Procedures, Operative / Q000009:adverse effects* / Q000379:methods