Incidence of Celiac Disease in Down Syndrome: A Longitudinal, Population-Based Birth Cohort Study.

American Academy of Pediatrics (AAP) guidelines for children with Down syndrome (DS) include assessment for celiac disease (CD), although data to support this recommendation have been inconsistent. We determined the incidence of CD among children with DS in a population-based birth cohort of children born from 1976 to 2000 in Olmsted County, Minnesota. Individuals with karyotype-confirmed DS and CD (using diagnosis codes, positive serology, and duodenal biopsies) were identified. The incidence of CD in DS was compared with the published incidence of CD for Olmsted County residents (17.4 [95% confidence interval = 15.2-19.6] per 100 000 person-years). Among 45 individuals with DS from the birth cohort, 3 (6.7%) were identified with positive celiac serology and confirmatory biopsies at ages 9, 12, and 23 years, for an incidence of 325 per 100 000 person-years. Thus, individuals with DS have more than 18 times the incidence rate of CD compared with the general population, supporting the AAP guidelines.

Gestational Age, Perinatal Characteristics, and Autism Spectrum Disorder: A Birth Cohort Study.

OBJECTIVE: To determine how gestational age relates to research-identified autism spectrum disorder (ASD-R) in the context of perinatal risk factors. STUDY DESIGN: This is a population-based cohort study using the 1994-2000 Olmsted County Birth Cohort. Children included were born and remained in Olmsted County after age 3 years. ASD-R status was determined from signs and symptoms abstracted from medical and educational records. Cox proportional hazards models were fit to identify associations between perinatal characteristics and ASD-R. RESULTS: The incidence of preterm birth (<37 weeks' gestation) was 8.6% among 7876 children. The cumulative incidence of ASD-R was 3.8% (95% CI 3.3-4.2) at 21 years of age. Compared with children born at full term, the risk of ASD-R appeared to be increased for children born preterm with unadjusted hazard ratios (HRs) of 2.62 (95% CI 0.65-10.57), 1.68 (95% CI 0.54-5.29), and 1.60 (95% CI 1.06-2.40) for children born extremely preterm, very preterm, and moderate-to-late preterm, respectively. In a multivariable model adjusted for perinatal characteristics, the associations were attenuated with adjusted HRs of 1.75 (95% CI 0.41-7.40), 1.24 (95% CI 0.38-4.01), and 1.42 (95% CI 0.93-2.15), for children born extremely preterm, very preterm, and moderate-to-late preterm, respectively. Among children with maternal history available (N = 6851), maternal psychiatric disorder was associated with ASD-R (adjusted HR 1.73, 95% CI 1.24-2.42). CONCLUSIONS: The increased risk of ASD-R among children born preterm relative to children born full term was attenuated by infant and maternal characteristics.

Association of Comorbid Mood and Anxiety Disorders With Autism Spectrum Disorder.

Importance: It is critical to evaluate the risk of comorbid psychiatric diagnoses to meet the needs of individuals with autism spectrum disorder (ASD). Objective: To examine whether individuals with ASD are at greater risk for comorbid diagnoses of depression, anxiety, or bipolar disorder. Design, Setting, and Participants: This cohort study used data from a population-based birth cohort of 31 220 individuals born in Olmsted County, Minnesota, from January 1, 1976, to December 31, 2000. Patients with research-identified ASD were previously identified using a multistep process that evaluated signs and symptoms abstracted from medical and educational records. For each of the 1014 patients with ASD, 2 age- and sex-matched referents who did not meet criteria for ASD were randomly selected from the birth cohort (n = 2028). Diagnosis codes for anxiety, depression, and bipolar disorders were electronically obtained using the Rochester Epidemiological Project records-linkage system. Data analysis was performed from July 1, 2018, to April 1, 2019. Main Outcomes and Measures: Cumulative incidence of clinically diagnosed depression, anxiety, and bipolar disorder through early adulthood in individuals with ASD compared with referents. Results: A total of 1014 patients with ASD (median age at last follow-up, 22.8 years [interquartile range, 18.4-28.0 years]; 747 [73.7%] male; 902 [89.0%] white) and 2028 referents (median age at last follow-up, 22.4 years [interquartile range, 18.8-26.2 years]; 1494 [73.7%] male; 1780 [87.8%] white) participated in the study. Patients with ASD were significantly more likely to have clinically diagnosed bipolar disorder (hazard ratio [HR], 9.34; 95% CI, 4.57-19.06), depression (HR, 2.81; 95% CI, 2.45-3.22), and anxiety (HR, 3.45; 95% CI, 2.96-4.01) compared with referents. Among individuals with ASD, the estimates of cumulative incidence by 30 years of age were 7.3% (95% CI, 4.8%-9.7%) for bipolar disorder, 54.1% (95% CI, 49.8%-58.0%) for depression, and 50.0% (95% CI, 46.0%-53.7%) for anxiety. Among referents, cumulative incidence estimates by 30 years of age were 0.9% (95% CI, 0.1%-1.7%) for bipolar disorder, 28.9% (95% CI, 25.7%-32.0%) for depression, and 22.2% (95% CI, 19.3%-25.0%) for anxiety. Conclusions and Relevance: The findings suggest that individuals with ASD may be at increased risk for clinically diagnosed depression, anxiety, and bipolar disorder compared with age- and sex-matched referents. This study supports the importance of early, ongoing surveillance and targeted treatments to address the psychiatric needs of individuals with ASD.

Patterns of neuropsychological changes after general anaesthesia in young children: secondary analysis of the Mayo Anesthesia Safety in Kids study.

BACKGROUND: We hypothesised that exposure to multiple, but not single, procedures requiring general anaesthesia before age 3 yr is associated with a specific pattern of deficits in processing speed and fine motor skills. METHODS: A secondary analysis (using factor and cluster analyses) of data from the Mayo Anesthesia Safety in Kids study was conducted, in which unexposed, singly exposed, and multiply exposed children born in Olmsted County, MN, USA from 1994 to 2007 were sampled using a propensity-guided approach and underwent neuropsychological testing at ages 8-12 or 15-20 yr. RESULTS: In the factor analysis, the data were well fit to a five factor model. For subjects multiply (but not singly) exposed to anaesthesia, a factor reflecting motor skills, visual-motor integration, and processing speed was significantly lower [standardised difference of -0.35 (95% confidence interval {CI} -0.57 to -0.13)] compared with unexposed subjects. No other factor was associated with exposure. Three groups were identified in the cluster analysis, with 106 subjects (10.6%) in Cluster A (lowest performance in most tests), 557 (55.9%) in Cluster B, and 334 (33.5%) in Cluster C (highest performance in most tests). The odds of multiply exposed children belonging to Cluster A was 2.83 (95% CI: 1.49-5.35; P=0.001) compared with belonging to Cluster B; there was no other significant association between exposure status and cluster membership. CONCLUSIONS: Multiple, but not single, exposures to procedures requiring general anaesthesia before age 3 yr are associated with a specific pattern of deficits in neuropsychological tests. Factors predicting which children develop the most pronounced deficits remain unknown.

Performance on the Operant Test Battery in young children exposed to procedures requiring general anaesthesia: the MASK study.

BACKGROUND: It is not known whether the neurotoxicity produced by anaesthetics administered to young animals can also occur in children. Exposure of infant macaques to ketamine impairs performance in selected domains of the Operant Test Battery (OTB), which can also be administered to children. This study determined whether a similar pattern of results on the OTB is found in children exposed to procedures requiring general anaesthesia before age 3 yr. METHODS: We analysed data from the Mayo Anesthesia Safety in Kids (MASK) study, in which unexposed, singly-exposed, and multiply-exposed children born in Olmsted County, MN, USA, from 1994 to 2007 were sampled using a propensity-guided approach and prospectively underwent OTB testing at ages 8-12 or 15-20 yr, using five tasks that generated 15 OTB test scores. RESULTS: In primary analysis, none of the OTB test scores depended upon anaesthesia exposure status when corrected for multiple comparisons. Cluster analysis identified four clusters of subjects, with cluster membership determined by relative performance on the OTB tasks. There was no evidence of association between exposure status and cluster membership. Exploratory factor analysis showed that the OTB scores loaded onto four factors. The score for one factor was significantly less in multiply-exposed children (mean standardised difference -0.28 [95% confidence interval, -0.55 to -0.01; P=0.04]), but significance did not survive a sensitivity analysis accounting for outlying values. CONCLUSIONS: These findings provide little evidence to support the hypothesis that children exposed to procedures requiring anaesthesia show deficits on OTB tasks that are similar to those observed in non-human primates.

Autism Spectrum Disorder: Incidence and Time Trends Over Two Decades in a Population-Based Birth Cohort.

We retrospectively identified autism spectrum disorder (ASD) incident cases among 31,220 individuals in a population-based birth cohort based on signs and symptoms uniformly abstracted from medical and educational records. Inclusive and narrow research definitions of ASD (ASD-RI and ASD-RN, respectively) were explored, along with clinical diagnoses of ASD (ASD-C) obtained from the records. The incidence of ASD-RI, ASD-RN, and ASD-C increased significantly from 1985 to 1998, then ASD-RI and ASD-RN plateaued while the rate of ASD-C continued to increase during 1998-2004. The rising incidence of research-defined ASD may reflect improved recognition and documentation of ASD signs and symptoms. Although the frequency of threshold ASD symptoms stabilized, the rate of ASD-C continued to increase, narrowing the gap between clinical ascertainment and symptom documentation.

Psychiatric Comorbidities Modify the Association Between Childhood ADHD and Risk for Suicidality: A Population-Based Longitudinal Study.

OBJECTIVE: The objective of this study was to evaluate the effect of psychiatric comorbidities on the association between childhood ADHD and suicidality among adults. METHOD: Subjects were recruited from a population-based birth cohort. Participating adult subjects with childhood ADHD and non-ADHD controls were administered a structured psychiatric interview to assess suicidality and psychiatric comorbidities. Associations were assessed using logistic regression. RESULTS: Compared with controls, ADHD cases were significantly more likely to meet criteria for suicidality. Subjects with childhood ADHD who met criteria for generalized anxiety disorder had a higher than expected risk of suicidality with an observed odds ratio of 10.94 (95% confidence interval [4.97, 24.08]) compared with an expected odds ratio of 4.86, consistent with a synergistic interaction effect. Significant synergistic interactions were also observed for hypomanic episode and substance-related disorders. CONCLUSION: Childhood ADHD is significantly associated with adult suicidal risk. Comorbidity between ADHD and some psychiatric disorders is associated with a higher suicidal risk than expected.

Neuropsychological and Behavioral Outcomes after Exposure of Young Children to Procedures Requiring General Anesthesia: The Mayo Anesthesia Safety in Kids (MASK) Study.

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.

Epidemiology of general anesthesia prior to age 3 in a population-based birth cohort.

BACKGROUND: Utilization of general anesthesia in children has important policy, economic, and healthcare delivery implications, yet there is little information regarding the epidemiology of these procedures in the United States. AIMS: The primary objective of this study was to describe in a geographically defined population the incidence of procedures requiring general anesthesia up to the child's third birthday, and the patient characteristics associated with receiving these procedures. A secondary objective was to determine the proportion of children in the population who meet the risk criteria promulgated by the Food and Drug Administration (FDA). METHODS: A retrospective cohort of children born from 1994 to 2007 in Olmsted County, MN was established. Birth certificate information and receipt of general anesthesia before age 3 were collected. Proportional hazard regressions were performed to evaluate the association between characteristics of children and incidence of general anesthesia. RESULTS: Among the 20 922 children in the cohort, 3120 (14.9%) underwent at least 1 general anesthesia before age 3. In multivariate regression, factors independently associated with receiving at least 1 procedure included prematurity, male sex, lower birth weight, cesarean delivery, a non-Hispanic mother, and a White mother, controlling for multiple gestation, number of children previously born, age, education, and marital status of the mother. Seven hundred and twenty-three children (3.5%) had at least 1 subsequent procedure. Estimated gestational age <32 weeks and low birth weight were independently associated with receiving repeated anesthesia. Eight hundred and twenty children (3.9%) had a single prolonged exposure above 3 hours, multiple exposures prior to age 3, or both. CONCLUSION: Approximately 1 in 7 children were exposed to at least 1 episode of general anesthesia before age 3, and approximately 1 in 4 children who received general anesthesia fall within the high-risk category as defined by the recent FDA warning. The apparent disparities in surgical utilization related to race and ethnicity in this study population deserve further exploration.

Adults With Persistent ADHD: Gender and Psychiatric Comorbidities-A Population-Based Longitudinal Study.

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.

Comparing Methods to Determine Persistence of Childhood ADHD Into Adulthood: A Prospective, Population-Based Study.

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; Mage = 27.0 years; 167 males, 65 females) and controls ( N = 335; Mage = 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.

Association between Exposure of Young Children to Procedures Requiring General Anesthesia and Learning and Behavioral Outcomes in a Population-based Birth Cohort.

BACKGROUND: Exposure of young animals to general anesthesia causes neurodegeneration and lasting behavioral abnormalities; whether these findings translate to children remains unclear. This study used a population-based birth cohort to test the hypothesis that multiple, but not single, exposures to procedures requiring general anesthesia before age 3 yr are associated with adverse neurodevelopmental outcomes. METHODS: A retrospective study cohort was assembled from children born in Olmsted County, Minnesota, from 1996 to 2000 (inclusive). Propensity matching selected children exposed and not exposed to general anesthesia before age 3 yr. Outcomes ascertained via medical and school records included learning disabilities, attention-deficit/hyperactivity disorder, and group-administered ability and achievement tests. Analysis methods included proportional hazard regression models and mixed linear models. RESULTS: For the 116 multiply exposed, 457 singly exposed, and 463 unexposed children analyzed, multiple, but not single, exposures were associated with an increased frequency of both learning disabilities and attention-deficit/hyperactivity disorder (hazard ratio for learning disabilities = 2.17 [95% CI, 1.32 to 3.59], unexposed as reference). Multiple exposures were associated with decreases in both cognitive ability and academic achievement. Single exposures were associated with modest decreases in reading and language achievement but not cognitive ability. CONCLUSIONS: These findings in children anesthetized with modern techniques largely confirm those found in an older birth cohort and provide additional evidence that children with multiple exposures are more likely to develop adverse outcomes related to learning and attention. Although a robust association was observed, these data do not determine whether anesthesia per se is causal.

What can large population-based birth cohort study ask about past, present and future of children with disorders of development, learning and behaviour?

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.

Epidemiology of Pediatric Critical Illness in a Population-Based Birth Cohort in Olmsted County, MN.

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.

Academic Achievement in Adults with a History of Childhood Attention-Deficit/Hyperactivity Disorder: A Population-Based Prospective Study.

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.

Role of individual-housing-based socioeconomic status measure in relation to smoking status among late adolescents with asthma.

PURPOSE: We aimed to assess whether smoking status among individuals in late adolescence (19-22 years) with asthma was associated with socioeconomic status (SES) defined by HOUSES, an individual-housing-based SES measure. METHODS: A population-based cross-sectional study was conducted among the 1988-1989 Olmsted County, Minnesota Birth Cohort, with physician-diagnosed asthma and that lived in the community during the study period (November 1, 2008-October 31, 2012). Using a z score for housing value, actual square footage, and numbers of bedrooms and bathrooms, HOUSES was formulated and categorized into quartiles. Smoking status (both current and past smoker) was compared among subjects with different SES as measured by HOUSES using logistic regression, adjusting for age and sex. RESULTS: Among 289 eligible subjects, 287 (99%) were successfully geo-coded to real property data for HOUSES. Of the 257 subjects whose smoke exposure was recorded, 70 (27%) had a history of smoking (either past or current). An inverse association was observed between HOUSES and smoking status after accounting for age, gender, and General Medical Examination status (adjusted OR = 0.39, 95% CI = 0.18-0.87 for comparing highest vs. lowest HOUSES in quartile; overall P = .02). CONCLUSIONS: A significant proportion of individuals with asthma in late adolescence was smokers during the study period, disproportionally affecting those with lower SES.

Mediating and Moderating Role of Depression, Conduct Disorder or Attention-Deficit/Hyperactivity Disorder in Developing Adolescent Substance Use Disorders: A Population-Based Study.

OBJECTIVE: To evaluate the mediating/moderating effects of common internalizing /externalizing disorders on the association between ADHD and adolescent substance use disorders (SUD) in a population-based birth cohort. METHODS: Among 5718 children in the birth cohort, 343 ADHD incident cases and 712 matched controls were identified. Psychiatric diagnoses prior to age 19 were classified into DSM-IV categories. The association between ADHD and SUD was summarized (hazard ratios (HR), 95% CI). The effect of depression, CD/ODD, anxiety was evaluated separately. RESULTS: Assessment of the joint effects of ADHD and each psychiatric disorder did not support a moderating effect of these disorders on SUD on additive scale. However, the association between ADHD and SUD was partially explained by a mediating role of these psychiatric disorders. CONCLUSION: For clinicians our results emphasize that depression (or CD/ODD) confers greater risk for SUD than ADHD alone. Early detection/treatment of SUD among adolescents with depression (or CD/ODD) is crucial regardless of ADHD.

Construction and Characterization of a Population-Based Cohort to Study the Association of Anesthesia Exposure with Neurodevelopmental Outcomes.

Exposure to general anesthesia at an early age has been associated with adverse neurodevelopmental outcomes in both animal and human studies, but some of these studies employed anesthetic agents that are no longer in clinical use. In this manuscript, we describe the methods used to construct a new population-based study cohort to study the association between early anesthetic exposure and subsequent neurodevelopmental outcomes. A birth cohort of all children born in Olmsted County, MN from January 1, 1996 to December 31, 2000 was identified. For each, school enrollment status in the Independent School District (ISD) 535 at age 5 or 6 and all episodes of anesthetic exposure before age 3 were identified. A study cohort was created by matching children enrolled in ISD 535 based on the propensity of receiving general anesthesia. Three analyses were performed to characterize the study cohort by comparing the birth and parental information, comorbidities, and socioeconomic status. The first analysis compared the characteristics of birth cohort children who were and were not enrolled in ISD 535. The second analysis evaluated the success of the propensity matching schemes in creating groups of children that were similar in measured characteristics except for anesthesia exposure. The third analysis compared the characteristics of children with anesthesia exposures who were and were not included in the final cohort based on propensity matching. Results of these analyses demonstrate only slight differences among the comparison groups, and therefore these are unlikely to compromise our future analysis of anesthetic exposure and neurodevelopmental outcomes.

Childhood Attention-Deficit/Hyperactivity Disorder, Sex, and Obesity: A Longitudinal Population-Based Study.

OBJECTIVE: To assess obesity rates during childhood and young adulthood in patients with attention-deficit/hyperactivity disorder (ADHD) and age- and sex-matched controls derived from a population-based birth cohort because cross-sectional studies suggest an association between ADHD and obesity. PATIENTS AND METHODS: Study subjects included patients with childhood ADHD (n=336) and age- and sex-matched non-ADHD controls (n=665) from a 1976 to 1982 birth cohort (N=5718). Height, weight, and stimulant treatment measurements were abstracted retrospectively from medical records documenting care provided from January 1, 1976, through August 31, 2010. The association between ADHD and obesity in patients with ADHD relative to controls was estimated using Cox models. RESULTS: Patients with attention-deficit/hyperactivity disorder were 1.23 (95% CI, 1.00-1.50; P<.05) times more likely to be obese during the follow-up period than were non-ADHD controls. This association was not statistically significant in either sex (female participants: hazard ratio [HR], 1.49; 95% CI, 0.98-2.27; P=.06; male participants HR, 1.17, 95% CI, 0.92-1.48; P=.20). Patients with ADHD who were not obese as of the date ADHD research diagnostic criteria were met were 1.56 (95% CI, 1.14-2.13; P<.01) times more likely to be obese during the subsequent follow-up than were controls. This association was statistically significant in female study subjects (HR, 2.02; 95% CI, 1.13-3.60; P=.02), but not in male participants (HR, 1.41; 95% CI, 0.97-2.05; P=.07). A higher proportion of patients with ADHD were obese after the age of 20 years compared with non-ADHD controls (34.4% vs 25.1%; P=.01); this difference was observed only in female patients (41.6% vs 19.2%). There were no differences in obesity rates between stimulant-treated and nontreated patients with ADHD. CONCLUSION: Childhood ADHD is associated with obesity during childhood and young adulthood in females. Treatment with stimulant medications is not associated with the development of obesity up to young adulthood.

Risk of Asthma in Late Preterm Infants: A Propensity Score Approach.

BACKGROUND: The risk of asthma, specifically in former late preterm infants, has not been well defined. Covariate imbalance and lack of controlling for this has led to inconsistent results in prior studies. OBJECTIVE: The objective of this study was to determine the risk of asthma in former late preterm infants using a propensity score approach. METHODS: The study was a population-based birth cohort study. Study subjects were all children born in Rochester, Minn, between 1976 and 1982. Asthma status during the first 7 years of life was assessed by applying predetermined criteria. The propensity score was formulated using 15 covariates by fitting a logistic regression model for late preterm birth versus term birth. We applied the propensity score method to match late preterm infants (34 0/7 to 36 6/7 weeks of gestation) to term infants (37 0/7 to 40 6/7 weeks of gestation) within a caliper of 0.2 standard deviation of logit of propensity score. RESULTS: Of the eligible 7040 infants, 5915 children had complete data. Before propensity score matching, late preterm infants had a higher risk of asthma (20 of 262, 7.6%) compared with full-term infants (272 of 5653, 4.8%) (P = .039). There was significant covariate imbalance between comparison groups. After matching with propensity scores, we found that former late preterm infants had a similar risk of asthma to the matched full-term infants (6.6% vs 7.7%, respectively, P = .61), and the result was consistent with covariate-adjustment Cox regression models controlling for significant covariates (P = .57). CONCLUSION: A late preterm birth history is not independently associated with childhood asthma, as the reported risk of asthma among former late preterm infants appears to be due to covariate imbalance.