WHAT'S KNOWN ON THIS SUBJECT:Exposure to virtually all anesthetic drugs has been shown to cause neurodegeneration in young animals. Studies of learning and cognition in children exposed to anesthesia and surgery have been few, have relied on single outcome measures, and have not controlled for comorbidity. WHAT THIS STUDY ADDS:In this study of children exposed to anesthesia/surgery before the age of 2, multiple group and individual measures of learning and behavior are examined by using a matched design with adjustment for comorbidity using 2 separate methods. 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 ϭ 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 ϭ 350) before the age of 2 were matched to unexposed controls (n ϭ 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 groupadministered 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 groupadministered 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.

Background Few studies of how exposure of children to anesthesia may affect neurodevelopment employ comprehensive neuropsychological assessments. This study tested the hypothesis that exposure to multiple, but not single, procedures requiring anesthesia before age 3 yr is associated with adverse neurodevelopmental outcomes. Methods Unexposed, singly exposed, and multiply exposed children born in Olmsted County, Minnesota, from 1994 to 2007 were sampled using a propensity-guided approach and underwent neuropsychological testing at ages 8 to 12 or 15 to 20 yr. The primary outcome was the Full-Scale intelligence quotient standard score of the Wechsler Abbreviated Scale of Intelligence. Secondary outcomes included individual domains from a comprehensive neuropsychological assessment and parent reports. Results In total, 997 children completed testing (411, 380, and 206 unexposed, singly exposed, and multiply exposed, respectively). The primary outcome of intelligence quotient did not differ significantly according to exposure status; multiply exposed and singly exposed children scoring 1.3 points (95% CI, −3.8 to 1.2; P = 0.32) and 0.5 points (95% CI, −2.8 to 1.9; P = 0.70) lower than unexposed children, respectively. For secondary outcomes, processing speed and fine motor abilities were decreased in multiply but not singly exposed children; other domains did not differ. The parents of multiply exposed children reported increased problems related to executive function, behavior, and reading. Conclusions Anesthesia exposure before age 3 yr was not associated with deficits in the primary outcome of general intelligence. Although secondary outcomes must be interpreted cautiously, they suggest the hypothesis that multiple, but not single, exposures are associated with a pattern of changes in specific neuropsychological domains that is associated with behavioral and learning difficulties.

WHAT'S KNOWN ON THIS SUBJECT: Attention-deficit/hyperactivity disorder (ADHD) has been viewed as a neurodevelopmental disorder, adversely affecting behavior and school performance, with studies suggesting increased risk for poor adult outcomes. However, no prospective studies have examined long-term outcomes of childhood ADHD in an epidemiologic sample.WHAT THIS STUDY ADDS: Our epidemiologic study indicates that adults with childhood ADHD are at increased risk for death from suicide. ADHD persists into adulthood in 29.3% of childhood ADHD cases, and 56.9% have $1 psychiatric disorder other than ADHD. abstract OBJECTIVE: We examined long-term outcomes of attention-deficit/ hyperactivity disorder (ADHD) in a population-based sample of childhood ADHD cases and controls, prospectively assessed as adults. METHODS:Adults with childhood ADHD and non-ADHD controls from the same birth cohort (N = 5718) were invited to participate in a prospective outcome study. Vital status was determined for birth cohort members. Standardized mortality ratios (SMRs) were constructed to compare overall and cause-specific mortality between childhood ADHD cases and controls. Incarceration status was determined for childhood ADHD cases. A standardized neuropsychiatric interview was administered.RESULTS: Vital status for 367 childhood ADHD cases was determined: 7 (1.9%) were deceased, and 10 (2.7%) were currently incarcerated. The SMR for overall survival of childhood ADHD cases versus controls was 1.88 (95% confidence interval [CI], 0.83-4.26; P = .13) and for accidents only was 1.70 (95% CI, 0.49-5.97; P = .41). However, the cause-specific mortality for suicide only was significantly higher among ADHD cases (SMR, 4.83; 95% CI, 1.14-20.46; P = .032). Among the childhood ADHD cases participating in the prospective assessment (N = 232; mean age, 27.0 years), ADHD persisted into adulthood for 29.3% (95% CI, 23.5-35.2). Participating childhood ADHD cases were more likely than controls (N = 335; mean age, 28.6 years) to have $1 other psychiatric disorder (56.9% vs 34.9%; odds ratio, 2.6; 95% CI, 1.8-3.8; P , .01). CONCLUSIONS:Childhood ADHD is a chronic health problem, with significant risk for mortality, persistence of ADHD, and long-term morbidity in adulthood. Dr Barbaresi conceptualized and designed the study, drafted the initial manuscript, and approved the final manuscript as submitted; Dr Colligan participated in the conceptualization, design, and conduct of the study, reviewed and revised the manuscript, and approved the final manuscript as submitted; Ms Weaver participated in the design of the study, carried out the initial analyses, revised and reviewed the manuscript, and approved the final manuscript as submitted; Dr Voigt participated in the design of the study, revised and reviewed the manuscript, and approved of the final manuscript as submitted; Ms Killian participated in the initial analyses, revised and reviewed the manuscript, and approved of the final manuscript as submitted; and Dr Katusic conceptualized and designed the stu...