Katusic, Slavica K.

A large cohort consisting of all children born to mothers from community provides ‘natural’ selection into different exposures and is a powerful resource for epidemiological research. A large population-based birth cohort with detailed systematic information already recorded, as part of longitudinal medical care, historical and current school data, detailed birth certificate data and all three resources available for every member of the birth cohort, are extremely rare. Our population-based birth cohort consists of all children born between 1976 and 2000 to mothers residing in Olmsted County, Minnesota, at the time of child's birth (N=39 890). In this paper, we provide a comprehensive report of the method describing the identification, the characteristics and longitudinal follow-up of each child (and family members) from the birth cohort, wealth of complementary resources of data and study measures and designs (retrospective, combined retrospective/prospective). In the last decade or so, we obtained scientific and clinically needed answers for incidence rates, potential risk/protective factors, treatment, comorbidities, outcomes, cost/usage and potential biases (that are always assessed and clinically interpreted) of many developmental learning and behavioural disorders (DLBDs) including learning and attention-deficit/hyperactivity disorders, intellectual disability, speech-language impairment and autism spectrum disorder. Many current and future questions related to DLBDs are remaining to be answered. The Olmsted County Birth Cohort (OCBC) is an example of a comprehensive, contemporary epidemiological research model for the development of similar research infrastructures, and its current and future results are important for replication and comparison with other population-based retrospective and prospective birth cohort studies.

Objectives: Investigations of pediatric critical illness typically focus on inpatient cohorts drawn from wide referral areas and diverse healthcare systems. Cohorts amenable to investigating the full spectrum of critical illness as it develops within a community have yet to be studied in the United States. Our objective was to provide the first epidemiologic report of the incidence and presentation of pediatric critical illness within a U.S. population-based birth cohort. Design: Retrospective cohort study. Setting: A geographically defined community (Olmsted, MN) with medical record linkage across all health systems. All ICU services are provided within a single children’s hospital. Patients: A birth cohort of children (n =9,441) born 2003–2007 in Olmsted County, MN. Measurements and Main Results: During the study period, there were a total of 15,277 ICU admissions to Mayo Clinic Children’s Hospital. A total of 577 birth cohort children accounted for 824 of these admissions during the 61,770 person-years of follow-up accumulated. Incidence of first-time ICU admission was 9.3 admits per 1,000 person-years. Admission rates were highest in the first year of life and then declined steadily. Respiratory problems were among the most common reasons for admission at any age and diagnoses reflect changes in health risk factors as children grow and develop over time. After 1 year old, a majority of children admitted have preexisting chronic comorbidities and/or prior ICU stays. In-hospital mortality occurred exclusively in children admitted prior to 5 days of age (n = 4). Seven children died after hospital discharge. Conclusions: This is the first report characterizing critical illness within a population-based birth cohort of U.S. children. The results demonstrate the changing incidence, presentation, and healthcare requirements associated with critical illness across the developmental spectrum as a population of children ages.

ABSTRACT Objective: Previous research on the developmental course of attention-deficit/hyperactivity disorder (ADHD) is limited by biased clinic-referred samples and other methodological problems. Thus, questions about adult academic outcomes associated with childhood ADHD remain unanswered. Thus, the objective of this study was to describe academic outcomes in adulthood among incident cases of research-identified childhood ADHD versus non-ADHD referents from a population-based birth cohort. Method: Young adults with research-identified childhood ADHD (N = 232; mean age 27.0 yr; 72.0% men) and referents (N = 335; mean age 28.6 yr; 62.7% men) from a 1976 to 1982 birth cohort (N = 5699) were invited to participate in a followup study and were administered an academic achievement battery consisting of the basic reading component of the Woodcock-Johnson III Tests of Achievement (WJ-III) and the arithmetic subtest of the Wide Range Achievement Test—Third Edition (WRAT-3). Outcomes were compared between the 2 groups using linear regression models, adjusted for age, sex, and comorbid learning disability status. Results: Childhood ADHD cases scored from 3 to 5 grade equivalents lower on all academic tests compared with referents, with mean (SD) standard scores of 95.7 (8.4) versus 101.8 (8.1) in basic reading; 95.0 (9.3) versus 101.9 (8.5) in letterword identification; 98.2 (8.6) versus 103.2 (9.2) in passage comprehension; 95.7 (9.1) versus 100.9 (9.0) in word attack; and 87.8 (12.9) versus 98.0 (12.0) in arithmetic. Conclusion: This is the first prospective, population-based study of adult academic outcomes of childhood ADHD. Our data provide evidence that childhood onset ADHD is associated with long-term underachievement in reading and math that may negatively impact ultimate educational attainment and occupational functioning in adulthood.

Objective: The aim of the study was to evaluate associations between ADHD and comorbid psychiatric disorders among adults from a population-based birth cohort. Method: Participants were recruited from all children born between 1976 and 1982 remaining in Rochester, Minnesota, after age 5. Participants with childhood ADHD ( n = 232; M age = 27.0 years; 72% men) and non-ADHD controls ( n = 335; M age = 28.6 years; 63% men) completed a structured interview (M.I.N.I. International Neuropsychiatric Interview) assessing current ADHD status and comorbid psychiatric disorders. Results: Among 232 with childhood ADHD, 68 (49 men, 19 women) had persistent adult ADHD. Compared with non-ADHD controls and non-persistent ADHD participants, adults with persistent ADHD were significantly more likely to have any or each of 12 psychiatric comorbidities. The associations retained significant or marginally significant when stratified by gender. Externalizing psychiatric disorders were more common in men (74%) and internalizing disorders in women (58%). Conclusion: Persistent ADHD is associated with an increased risk of comorbid psychiatric disorders in adult men and women.

Objective: To compare the rate of persistence of ADHD into adulthood as determined by a norm-referenced versus non-norm-referenced diagnostic interview, and by standardized questionnaires. Method: Adults from a birth cohort, including research-identified childhood ADHD cases ( N = 232; M age = 27.0 years; 167 males, 65 females) and controls ( N = 335; M age = 28.6 years; 210 males, 125 females), were administered the M.I.N.I. International Neuropsychiatric Interview, the Murphy–Barkley Symptoms Checklist (MB), and the Wender Utah Rating Scale (WURS) Results: Among the childhood ADHD cases, 29.3% fulfilled criteria for adult ADHD using a norm-referenced approach to M.I.N.I. scoring, versus 13.8% using published M.I.N.I. criteria. Among participants meeting norm-referenced diagnostic criteria, 41.8% and 69.1% were classified as adult ADHD using the MB and WURS, respectively. Conclusion: A non-norm-referenced approach resulted in a significant underestimate of the rate of adult ADHD. Reliance on either of two adult ADHD questionnaires would have further reduced this estimate.

BACKGROUND AND OBJECTIVE:There is ongoing concern that stimulant medications may adversely affect growth. In a sample of attention-deficit/hyperactivity disorder (ADHD) cases and controls from a population-based birth cohort, we assessed growth and the association between stimulant treatment and growth.METHODS:Subjects included childhood ADHD cases (N = 340) and controls (N = 680) from a 1976 to 1982 birth cohort (N = 5718). Height and stimulant treatment information were abstracted from medical records and obtained during a prospective, adult follow-up study. For each subject, a parametric penalized spline smoothing method modeled height over time, and the corresponding height velocity was calculated as the first derivative. Peak height velocity (PHV) age and magnitude were estimated from the velocity curves. Among stimulant-treated ADHD cases, we analyzed height Z scores at the beginning, at the end, and 24 months after the end of treatment.RESULTS:Neither ADHD itself nor treatment with stimulants was associated with differences in magnitude of PHV or final adult height. Among boys treated with stimulants, there was a positive correlation between duration of stimulant usage before PHV and age at PHV (r = 0.21, P = .01). There was no significant correlation between duration of treatment and change in height Z scores (r = −0.08 for beginning vs end change, r = 0.01 for end vs 24 months later change). Among the 59 ADHD cases treated for ≥3 years, there was a clinically insignificant decrease in mean Z score from beginning (0.48) to end (0.33) of treatment (P = .06).CONCLUSIONS:Our findings suggest that ADHD treatment with stimulant medication is not associated with differences in adult height or significant changes in growth.

ABSTRACTObjective:The aim of the study was to determine whether docosahexaenoic acid (DHA) supplementation improves the behavior of children with autism.Methods:A group of 3‐ to 10‐year‐old children with autism were randomized in a double‐blind fashion to receive a supplement containing 200 mg of DHA or a placebo for 6 months. The parents and the investigator completed the Clinical Global Impressions‐Improvement scale to rate changes in core symptoms of autism after 3 and 6 months. The parents completed the Child Development Inventory and the Aberrant Behavior Checklist, and both parents and teachers completed the Behavior Assessment Scale for Children (BASC) at enrollment and after 6 months.Results:A total of 48 children (40 [83%] boys, mean age [standard deviation] 6.1 [2.0] years) were enrolled; 24 received DHA and 24 placebo. Despite a median 431% increase in total plasma DHA levels after 6 months, the DHA group was not rated as improved in core symptoms of autism compared to the placebo group on the CGI‐I. Based on the analysis of covariance models adjusted for the baseline rating scores, parents (but not teachers) provided a higher average rating of social skills on the BASC for the children in the placebo group compared to the DHA group (P = 0.04), and teachers (but not parents) provided a higher average rating of functional communication on the BASC for the children in the DHA group compared to the placebo group (P = 0.02).Conclusions:Dietary DHA supplementation of 200 mg/day for 6 months does not improve the core symptoms of autism. Our results may have been limited by inadequate sample size.

BACKGROUND AND OBJECTIVE: Previous studies suggest that former late preterm infants are at increased risk for learning and behavioral problems compared with term infants. These studies have primarily used referred clinical samples of children followed only until early school age. Our objective was to determine the cumulative incidence of attention deficit/hyperactivity disorder (ADHD) and learning disabilities (LD) in former late preterm versus term infants in a population-based birth cohort. METHODS: Subjects included all children born 1976 to 1982 in Rochester, MN who remained in the community after 5 years. This study focused on the comparison of subjects in 2 subgroups, late preterm (34 to <37 weeks) and term (37 to <42 weeks). School and medical records were available to identify individuals who met research criteria for ADHD and LD in reading, written language, and math. The Kaplan-Meier method was used to estimate the cumulative incidence of each condition by 19 years of age. Cox models were fit to evaluate the association between gestational age group and condition, after adjusting for maternal education and perinatal complications. RESULTS: We found no statistically significant differences in the cumulative incidence of ADHD or LD between the late preterm (N = 256) versus term (N = 4419) groups: ADHD (cumulative incidence by age 19 years, 7.7% vs 7.2%; P = .84); reading LD (14.2% vs 13.1%; P = .57); written language LD (13.5% vs 15.7%; P = .36), and math LD (16.1% vs 15.5%; P = .89). CONCLUSIONS: These data from a population-based birth cohort indicate that former late preterm infants have similar rates of LD and ADHD as term infants.

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.

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.