Voigt, Robert G.

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.

To determine the range of neurodevelopmental diagnoses associated with intermediate (45-54 repeats) and premutation (55-200 repeats) range cytosine-guanine-guanine fragile X expansions, the medical records of children with intermediate or premutation range expansions were retrospectively reviewed, and all neurodevelopmental diagnoses were abstracted. Twenty-nine children (9 female, 20 male; age, 13 months to 17 years) with intermediate (n = 25) or premutation (n = 4) range expansions were identified with neurodevelopmental diagnoses, including global developmental delay/intellectual disability (n = 15), language and learning disorders (n = 9), attention-deficit hyperactivity disorder (n = 5), epilepsy (n = 5), and motor disorders (n = 12), including 2 boys younger than 4 years of age with tremor and ataxia. Thus, children with intermediate or premutation range fragile X cytosine-guanine-guanine expansions may be more susceptible than children without such expansions to other processes, both genetic and environmental, that contribute to neurodevelopmental disability.

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.

OBJECTIVE: We determined the incidence of written-language disorder (WLD) among children with and without attention-deficit/hyperactivity disorder (ADHD) in a population-based birth cohort. METHODS: Subjects included a birth cohort of all children born in 1976–1982 who remained in Rochester, Minnesota, after 5 years of age (N = 5718). Information from medical, school, and private tutorial records was abstracted. Cumulative incidences of WLD with or without reading disability (RD), identified with any of 3 formulas, among children with and without ADHD and hazard ratios (HRs) were calculated. RESULTS: For both genders, the cumulative incidence of WLD by 19 years of age was significantly higher for children with ADHD than for children without ADHD (boys: 64.5% vs 16.5%; girls: 57.0% vs 9.4%). The magnitude of association between ADHD and WLD with RD was significantly higher for girls than for boys (adjusted HR: girls: 9.8; boys: 4.2; P < .001). However, this was not true for WLD without RD (adjusted HR: girls: 7.4; boys: 6.6; P = .64). CONCLUSIONS: ADHD is strongly associated with an increased risk of WLD (with or without RD) for both boys and girls. Girls with ADHD are at higher risk of having WLD with RD compared with boys with ADHD, whereas boys and girls are at the same risk of having WLD without RD.

OBJECTIVE: To determine the incidence of reading disability (RD) among children with and without research-identified attention-deficit/hyperactivity disorder (ADHD), separately according to gender, in a population-based birth cohort. METHOD: Subjects included all children born in 1976–1982 remaining in Rochester, Minnesota, after 5 years of age (n = 5718). Information from medical, school, and private tutorial records was abstracted. Cumulative incidence of RD, by any of 3 RD formulas, in children with and without ADHD and corresponding hazard ratios (HRs) were calculated separately according to gender. RESULTS: Cumulative incidence of RD by the age of 19 years was significantly higher in children with ADHD (51% in boys, 46.7% in girls) compared with those without ADHD (14.5% in boys, 7.7% in girls). Among children with ADHD, the risk for RD was similar in boys versus girls (HR: 1.0). However, among children without ADHD, boys were 2.0 times more likely than girls to meet RD criteria. Among girls, the HR for the risk for RD associated with ADHD (versus those without ADHD) was 8.1 (95% confidence interval: 5.7–11.5), which was significantly higher than the corresponding HR among boys (3.9 [95% confidence interval: 3.2–4.9]). CONCLUSIONS: The risk for RD is significantly greater among children with ADHD compared with those without ADHD. Among children with ADHD, the risk for RD is the same for boys and girls. However, among children without ADHD, boys are more at risk for RD than girls. Among girls, the magnitude of increased risk for RD associated with ADHD is nearly twice that among boys, because girls without ADHD are less likely to have RD than boys without ADHD.

OBJECTIVE: To determine whether children with autism have an increased incidence of gastrointestinal symptoms compared with matched control subjects in a population-based sample. DESIGN/METHODS: In a previous study including all of the residents of Olmsted County, Minnesota, aged <21 years between 1976 and 1997, we identified 124 children who fulfilled criteria on the basis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, for a research diagnosis of autism. Two matched control subjects were identified for each case subject. Through the Rochester Epidemiology Project, all medical diagnoses, are indexed for computerized retrieval. Gastrointestinal diagnoses before 21 years of age were grouped into 5 categories: (1) constipation; (2) diarrhea; (3) abdominal bloating, discomfort, or irritability; (4) gastroesophageal reflux or vomiting; and (5) feeding issues or food selectivity. The cumulative incidence of each category was calculated by using the Kaplan-Meier method. Cox proportional hazards models were fit to estimate the risk ratios (case subjects versus control subjects) and corresponding 95% confidence intervals. RESULTS: Subjects were followed to median ages of 18.2 (case subjects) and 18.7 (control subjects) years. Significant differences between autism case and control subjects were identified in the cumulative incidence of constipation (33.9% vs 17.6%) and feeding issues/food selectivity (24.5% vs 16.1). No significant associations were found between autism case status and overall incidence of gastrointestinal symptoms or any other gastrointestinal symptom category. CONCLUSIONS: As constipation and feeding issues/food selectivity often have a behavioral etiology, data suggest that a neurobehavioral rather than a primary organic gastrointestinal etiology may account for the higher incidence of these gastrointestinal symptoms in children with autism.

This cross-sectional study examines the relationship between parenting stress and concerns identified by developmental screening and their effects on parents' decisions to seek medical care for their children. A total of 182 parents completed both the Parenting Stress Index (PSI) and the Parents' Evaluation of Developmental Status (PEDS) when their children were admitted to a sick child care program that provides parents the option of requesting medical evaluations for their children with mild acute illnesses. Although 31.6% of parents (N = 62) requested medical evaluations, neither PSI nor PEDS scores were associated with these requests. However, PEDS scores indicating significant parental concerns about their child's development or behavior predicted clinically significant levels of parenting stress on the PSI (odds ratio 4.9; 95% confidence interval, 1.5-15.9; P = .007). Primary pediatric health care providers who routinely perform developmental screening need to consider this relationship when interpreting developmental screening results and offer supportive and referral services to families as needed.

The reasons underlying parents' decisions to seek medical evaluations for their mildly ill children are not well understood. This cross-sectional study tracked parents' requests for on-site medical evaluations at a sick child care program. A logistic regression model identified factors associated with parents' decisions to seek medical evaluations for their children based on the data from parent-completed questionnaires. A convenience sample of 196 parents completed all questionnaires; 62 (31.6%) parents sought medical evaluations. Parents were more likely to seek medical evaluations if they were concerned about missing work (odds ratio = 8.6; 95% confidence interval, 3.3-22.0; P = .0001), if they smoked (odds ratio = 3.7; 95% confidence interval, 1.1-12.4; P = .037), or if their spouse's highest educational attainment was some high school (odds ratio = 0.4; 95% confidence interval, 0.1-1.0; P = .044). The data highlight the problems working parents have in accessing health care during usual working hours and the potential value of convenient health care programs.

The Cognitive Adaptive Test/ Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) was designed for use by primary pediatric health care providers to identify children with developmental delays. This study assesses the concurrent and predictive validity of CAT/CLAMS developmental quotient (DQ) scores and the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development in healthy children without risk factors for developmental delay. Overall CAT/CLAMS DQ scores correlated significantly with Bayley MDI scores at both 12 (r=0.393; p=0.008) and 30 months (r=0.742; p=0.0001) of age. Overall CAT/CLAMS DQ scores at 12 months of age also correlated modestly with Bayley MDI scores at 30 months of age (r=0.181; p=0.036). Despite its modest predictive validity at 12 months, its satisfactory concurrent validity plus its ease and speed of administration make the CAT/CLAMS a reasonable choice for assessment of early development by primary pediatric health care providers.