title: Behavior and development in children and age at the time of first anesthetic exposure.
abstract: BACKGROUND
  Several experimental studies have suggested that early exposure to anesthetic agents, i.e., before completion of synaptogenesis, can result in widespread apoptotic neuronal degeneration and late cognitive impairment, but human data are lacking. The authors performed a retrospective pilot study to test the feasibility and calculate sample sizes for a larger epidemiologic study of disturbed neurobehavioral development as a function of age at the time of first anesthetic exposure. Pediatric urological procedures were selected because the timing of surgery depends mainly on the age at which a diagnosis is made.
  
  
  METHODS
  Neurobehavioral development was assessed using the validated 120-item parental Child Behavior CheckList/4-18 in 314 children who were operated for pediatric urological procedures between the ages of 0 and 6 yr.
  
  
  RESULTS
  Of 243 questionnaires returned, the total problem score was clinically deviant in 41 (23%) of children aged less than 24 months at the time of first surgery and 13 (20%) aged greater than 24 months. Crude and adjusted odds ratios for a clinically deviant Child Behavior CheckList/4-18 score increased with younger age at the time of surgery, but the confidence intervals were very wide. Adjusted odds ratio was 1.38 (0.59-3.22) when operated at age less than 6 months, 1.19 (0.45-3.18) when operated between 6 and 12 months of age, and 1.20 (0.45-3.20) when operated between 12 and 24 months (using operated at greater than 24 months of age as reference category). A properly powered cohort study would require at least 2,268 children.
  
  
  CONCLUSIONS
  Children undergoing urologic surgery at age less than 24 months showed more behavioral disturbances than children in whom surgery was performed after age 2 yr, although the results were not statistically significant. To confirm or refute an effect of anesthesia on cognitive development, at least 2,268 children need to be studied. With retrospective study designs, residual confounding remains an issue that can only be solved in prospective randomized studies.
authors.affiliation: Department of Anesthesiology, University Medical Center, Utrecht, The Netherlands. c.j.kalkman@umcutrecht.nl
authors.forename: Cor J
authors.initials: CJ
authors.lastname: Kalkman
authors.forename: Linda
authors.initials: L
authors.lastname: Peelen
authors.forename: Karel G
authors.initials: KG
authors.lastname: Moons
authors.forename: Morna
authors.initials: M
authors.lastname: Veenhuizen
authors.forename: Marcel
authors.initials: M
authors.lastname: Bruens
authors.forename: Gerben
authors.initials: G
authors.lastname: Sinnema
authors.forename: Tom P
authors.initials: TP
authors.lastname: de Jong
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000768:Anesthesia, General / Q000009:adverse effects*; D018681:Anesthetics, General / Q000009:adverse effects*; D002648:Child; D002653:Child Behavior Disorders / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D016017:Odds Ratio; D010865:Pilot Projects; D012189:Retrospective Studies; D018401:Sample Size; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D013520:Urologic Surgical Procedures
chemical_list: D018681:Anesthetics, General