title: Early exposure to anesthesia and learning disabilities in a population-based birth cohort.
abstract: BACKGROUND
  Anesthetic drugs administered to immature animals may cause neurohistopathologic changes and alterations in behavior. The authors studied association between anesthetic exposure before age 4 yr and the development of reading, written language, and math learning disabilities (LD).
  
  
  METHODS
  This was a population-based, retrospective birth cohort study. The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota, from 1976 to 1982 and who remained in the community at 5 yr of age were reviewed to identify children with LD. Cox proportional hazards regression was used to calculate hazard ratios for anesthetic exposure as a predictor of LD, adjusting for gestational age at birth, sex, and birth weight.
  
  
  RESULTS
  Of the 5,357 children in this cohort, 593 received general anesthesia before age 4 yr. Compared with those not receiving anesthesia (n = 4,764), a single exposure to anesthesia (n = 449) was not associated with an increased risk of LD (hazard ratio = 1.0; 95% confidence interval, 0.79-1.27). However, children receiving two anesthetics (n = 100) or three or more anesthetics (n = 44) were at increased risk for LD (hazard ratio = 1.59; 95% confidence interval, 1.06-2.37, and hazard ratio = 2.60; 95% confidence interval, 1.60-4.24, respectively). The risk for LD increased with longer cumulative duration of anesthesia exposure (expressed as a continuous variable) (P = 0.016).
  
  
  CONCLUSIONS
  Exposure to anesthesia was a significant risk factor for the later development of LD in children receiving multiple, but not single anesthetics. These data cannot reveal whether anesthesia itself may contribute to LD or whether the need for anesthesia is a marker for other unidentified factors that contribute to LD.
authors.affiliation: Department of Anesthesiology, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Wilder
authors.forename: Randall P
authors.initials: RP
authors.lastname: Flick
authors.forename: Juraj
authors.initials: J
authors.lastname: Sprung
authors.forename: Slavica K
authors.initials: SK
authors.lastname: Katusic
authors.forename: William J
authors.initials: WJ
authors.lastname: Barbaresi
authors.forename: Christopher
authors.initials: C
authors.lastname: Mickelson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gleich
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Schroeder
authors.forename: Amy L
authors.initials: AL
authors.lastname: Weaver
authors.forename: David O
authors.initials: DO
authors.lastname: Warner
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000768:Anesthesia, General / Q000009:adverse effects*; D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D018686:Anesthetics, Intravenous / Q000009:adverse effects*; D002675:Child, Preschool; D015331:Cohort Studies; D005220:Fathers; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007859:Learning Disabilities / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D008297:Male; D008910:Minnesota / Q000453:epidemiology; D009035:Mothers; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011247:Pregnancy; D011248:Pregnancy Complications; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous