Robert C. Colligan

Cognitive and Behavioral Outcomes After Early Exposure to Anesthesia and Surgery

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.

Attention-Deficit/Hyperactivity Disorder After Early Exposure to Procedures Requiring General Anesthesia

OBJECTIVE To study the association between exposure to procedures performed under general anesthesia before age 2 years and development of attention-deficit/hyperactivity disorder (ADHD). PATIENTS AND METHODS Study patients included all children born between January 1, 1976, and December 31, 1982, in Rochester, MN, who remained in Rochester after age 5. Cases of ADHD diagnosed before age 19 years were identified by applying stringent research criteria. Cox proportional hazards regression assessed exposure to procedures requiring general anesthesia (none, 1, 2 or more) as a predictor of ADHD using a stratified analysis with strata based on a propensity score including comorbid health conditions. RESULTS Among the 5357 children analyzed, 341 ADHD cases were identified (estimated cumulative incidence, 7.6%; 95% confidence interval [CI], 6.8%-8.4%). For children with no postnatal exposure to procedures requiring anesthesia before the age of 2 years, the cumulative incidence of ADHD at age 19 years was 7.3% (95% CI, 6.5%-8.1%). For single and 2 or more exposures, the estimates were 10.7% ( 95% CI, 6.8%-14.4%) and 17.9% ( 95% CI, 7.2%-27.4%), respectively. After adjusting for gestational age, sex, birth weight, and comorbid health conditions, exposure to multiple (hazard ratio, 1.95; 95% CI, 1.03-3.71), but not single (hazard ratio,1.18; 95% CI, 0.79-1.77), procedures requiring general anesthesia was associated with an increased risk for ADHD. CONCLUSION Children repeatedly exposed to procedures requiring general anesthesia before age 2 years are at increased risk for the later development of ADHD even after adjusting for comorbidities.

Long-term school outcomes for children with attention-deficit/hyperactivity disorder: a population-based perspective.

Objective: The purpose of this study was to compare long-term school outcomes (academic achievement in reading, absenteeism, grade retention, and school dropout) for children with attention-deficit/hyperactivity disorder (AD/HD) versus those without AD/HD. Methods: Subjects included 370 children with research-identified AD/HD from a 1976–1982 population-based birth cohort (N = 5718) and 740 non-AD/HD control subjects from the same birth cohort, matched by gender and age. All subjects were retrospectively followed from birth until a median age of 18.4 years (AD/HD cases) or 18.3 years (non-AD/HD controls). The complete school record for each subject was reviewed to obtain information on reading achievement (last available California Achievement Test reading score), absenteeism (number/percentage of school days absent at each grade level), grade retention (having to repeat an entire grade in the subsequent school year), and school dropout (failure to graduate from high school). Results: Median reading achievement scores at age 12.8 years (expressed as a national percentile) were significantly different for AD/HD cases and non-AD/HD controls (45 vs 73). Results were similar for both boys and girls with AD/HD. Median percentage of days absent was statistically significantly higher for children with AD/HD versus those without AD/HD, although the difference was relatively small in absolute number of days absent. Subjects with AD/HD were three times more likely to be retained a grade. Similarly, subjects with AD/HD were 2.7 times more likely to drop out before high school graduation (22.9%) than non-AD/HD controls (10.0%). Conclusions: The results of this population-based study clearly demonstrate the association between AD/HD and poor long-term school outcomes.

Incidence of Reading Disability in a Population-Based Birth Cohort, 1976–1982, Rochester, Minn

OBJECTIVE To report the incidence of reading disability among school-aged children. SUBJECTS AND METHODS In this population-based, retrospective birth cohort study, subjects included all 5718 children born between 1976 and 1982 who remained in Rochester, Minn, after the age of 5 years. Based on records from all public and nonpublic schools, medical facilities, and private tutorial services and on results of all individually administered IQ and achievement tests, extensive medical, educational, and socioeconomic information were abstracted. Reading disability was established with use of research criteria based on 4 formulas (2 regression-based discrepancy, 1 non-regression-based discrepancy, and 1 low achievement). RESULTS Cumulative incidence rates of reading disability varied from 5.3% to 11.8% depending on the formula used. Boys were 2 to 3 times more likely to be affected than girls, regardless of the identification methods applied. CONCLUSIONS In this population-based birth cohort, reading disability was common among school-aged children and significantly more frequent among boys than girls, regardless of definition.

Math learning disorder: incidence in a population-based birth cohort, 1976-82, Rochester, Minn.

OBJECTIVE To report the incidence of math learning disorder (Math LD) among school-aged children, overall and by gender. To compare incidence estimates obtained by using three different methods to identify Math LD cases. To assess the extent to which children manifest Math LD alone, versus Math LD with comorbid reading disorder. METHODS This is a population-based, retrospective, birth cohort study. Subjects included all children born 1976-82 who remained in Rochester, Minn after age 5 (N = 5718). Using records from all public and private schools, medical facilities, and private tutorial services, all individually administered intelligence quotient and achievement tests and extensive medical, educational, and socioeconomic information were abstracted. Math LD was established using research criteria based on 3 formulas (regression-based discrepancy, nonregression-based discrepancy, low achievement). RESULTS Cumulative incidence rates of Math LD by age 19 years varied from 5.9% to 13.8% according to the formula used. Boys were more likely to be affected than girls, with relative risk ratios from 1.6 to 2.2 depending on the formula applied. Many children with Math LD (35% to 56.7%, depending on the formula used to define Math LD) did not have a comorbid reading disorder. CONCLUSIONS These results, from a community-based birth cohort, suggest that Math LD is common among schoolchildren, and is significantly more frequent among boys than girls, regardless of definition. Many children with Math LD do not have an associated reading disorder.

Mortality, ADHD, and Psychosocial Adversity in Adults With Childhood ADHD: A Prospective Study

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.

Optimists vs Pessimists: Survival Rate Among Medical Patients Over a 30-Year Period

OBJECTIVE To examine explanatory style (how people explain life events) as a risk factor for early death, using scores from the Optimism-Pessimism scale of the Minnesota Multiphasic Personality Inventory (MMPI). SUBJECTS AND METHODS A total of 839 patients completed the MMPI between 1962 and 1965 as self-referred general medical patients. Thirty years later, the vital status of each of these patients was ascertained. RESULTS Of the 839 patients, 124 were classified as optimistic, 518 as mixed, and 197 as pessimistic. Follow-up was available for 723 patients. Among these, a 10-point T-score increase on the Optimism-Pessimism scale (e.g., more pessimistic) was associated with a 19% increase in the risk of mortality. CONCLUSION A pessimistic explanatory style, as measured by the Optimism-Pessimism scale of the MMPI, is significantly associated with mortality.

Childhood ADHD is Strongly Associated with a Broad Range of Psychiatric Disorders during Adolescence: a Population-Based Birth Cohort Study

BACKGROUND To evaluate associations between attention-deficit/hyperactivity disorder (ADHD) and comorbid psychiatric disorders using research-identified incident cases of ADHD and population-based controls. METHODS Subjects included a birth cohort of all children born 1976-1982 remaining in Rochester, MN after age five (n = 5,718). Among them we identified 379 ADHD incident cases and 758 age-gender matched non-ADHD controls, passively followed to age 19 years. All psychiatric diagnoses were identified and abstracted, but only those confirmed by qualified medical professionals were included in the analysis. For each psychiatric disorder, cumulative incidence rates for subjects with and without ADHD were estimated using the Kaplan-Meier method. Corresponding hazard ratios (HR) were estimated using Cox models adjusted for gender and mothers age and education at the subjects birth. The association between ADHD and the likelihood of having an internalizing or externalizing disorder was summarized by estimating odds ratios (OR). RESULTS Attention-deficit/hyperactivity disorder was associated with a significantly increased risk of adjustment disorders (HR = 3.88), conduct/oppositional defiant disorder (HR = 9.54), mood disorders (HR = 3.67), anxiety disorders (HR = 2.94), tic disorders (HR = 6.53), eating disorders (HR = 5.68), personality disorders (HR = 5.80), and substance-related disorders (HR = 4.03). When psychiatric comorbidities were classified on the internalization-externalization dimension, ADHD was strongly associated with coexisting internalizing/externalizing (OR = 10.6), or externalizing-only (OR = 10.0) disorders. CONCLUSION This population-based study confirms that children with ADHD are at significantly increased risk for a wide range of psychiatric disorders. Besides treating the ADHD, clinicians should identify and provide appropriate treatment for psychiatric comorbidities.

Long-term stimulant medication treatment of attention-deficit/hyperactivity disorder: results from a population-based study.

ABSTRACT: The purpose of this study was to offer detailed information about stimulant medication treatment provided throughout childhood to 379 children with research-identified attention-deficit hyperactivity disorder (ADHD) in the 1976–1982 Rochester, MN, birth cohort. Subjects were retrospectively followed from birth until a mean of 17.2 years of age. The complete medical record of each subject was reviewed. The history and results of each episode of stimulant treatment were compared by gender, DSMIV subtype of ADHD, and type of stimulant medication. Overall, 77.8% of subjects were treated with stimulants. Boys were 1.8 times more likely than girls to be treated. The median age at initiation (9.8 years), median duration of treatment (33.8 months), and likelihood of developing at least one side effect (22.3%) were not significantly different by gender. Overall, 73.1% of episodes of stimulant treatment were associated with a favorable response. The likelihood of a favorable response was comparable for boys and girls. Treatment was initiated earlier for children with either ADHD combined type or ADHD hyperactive-impulsive type than for children with ADHD predominantly inattentive type and duration of treatment was longer for ADHD combined type. There was no association between DSM-IV subtype and likelihood of a favorable response or of side effects. Dextroamphetamine and methylphenidate were equally likely to be associated with a favorable response, but dextroamphetamine was more likely to be associated with side effects. These results demonstrate that the effectiveness of stimulant medication treatment of ADHD provided throughout childhood is comparable to the efficacy of stimulant treatment demonstrated in clinical trials.

Modifiers of Long-term School Outcomes for Children with Attention-deficit/hyperactivity Disorder: Does Treatment with Stimulant Medication Make a Difference? Results from a Population-based Study

Objective: The purpose of this study was to describe the significance of potential modifiers of long-term school outcomes among children with attention-deficit/hyperactivity disorder (AD/HD), including treatment with stimulant medication. Methods: Subjects included 370 children with research-identified AD/HD from a 1976–1982 population-based birth cohort (N = 5718). In a companion study, the complete school record for each subject was reviewed to obtain information on reading achievement, absenteeism, grade retention, and school dropout. Data on type of stimulant, dose, age at initiation of treatment, and start/stop dates were collected from medical and school records, available for all subjects. Results: Treatment with stimulants was associated with decreased rates of absenteeism; longer duration of treatment was also associated with decreased absenteeism rates. There was a modest positive correlation (r = .15, p = .012) between average daily stimulant dose and last reading score. Cases treated with stimulants were 1.8 times less likely to subsequently be retained a grade (95% confidence interval: 1.01–3.2; p = .047). The proportion of school dropout was similar between treated and not treated cases (22.2% vs 25.8%, p = .54). Other potential modifiers of school outcomes (sociodemographic risk factors, presence of comorbid learning or psychiatric disorders, and receipt of special educational services) were also examined and found to be associated with poorer outcomes. Conclusions: In this birth cohort, stimulant treatment of children with AD/HD was associated with improved reading achievement, decreased school absenteeism, and decreased grade retention. This study provides support for efforts to ensure that children with AD/HD receive appropriate long-term medical treatment.