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.

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.

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.

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.

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.

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.

Dietary docosahexaenoic acid supplementation in children with autism.

OBJECTIVE: 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.

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 mother's age and education at the subject's 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.

Direct medical costs of constipation from childhood to early adulthood: a population-based birth cohort study.

BACKGROUND: Although direct medical costs for constipation-related medical visits are thought to be high, to date there have been no studies examining whether longitudinal resource use is persistently elevated in children with constipation. Our aim was to estimate the incremental direct medical costs and types of health care use associated with constipation from childhood to early adulthood. METHODS: A nested case-control study was conducted to evaluate the incremental costs associated with constipation. The original sample consisted of 5718 children in a population-based birth cohort who were born during 1976 to 1982 in Rochester, MN. The cases included individuals who presented to medical facilities with constipation. The controls were matched and randomly selected among all noncases in the sample. Direct medical costs for cases and controls were collected from the time subjects were between 5 and 18 years of age or until the subject emigrated from the community. RESULTS: We identified 250 cases with a diagnosis of constipation in the birth cohort. Although the mean inpatient costs for cases were $9994 (95% Confidence interval [CI] 2538-37,201) compared with $2391 (95% CI 923-7452) for controls (P = 0.22) during the time period, the mean outpatient costs for cases were $13,927 (95% CI 11,325-16,525) compared with $3448 (95% CI 3771-4621) for controls (P < 0.001) during the same time period. The mean annual number of emergency department visits for cases was 0.66 (95% CI 0.62-0.70) compared with 0.34 (95% CI 0.32-0.35) for controls (P < 0.0001). CONCLUSIONS: Individuals with constipation have higher medical care use. Outpatient costs and emergency department use were significantly greater for individuals with constipation from childhood to early adulthood.

Neuraxial labor analgesia for vaginal delivery and its effects on childhood learning disabilities.

BACKGROUND: In prior work, children born to mothers who received neuraxial anesthesia for cesarean delivery had a lower incidence of subsequent learning disabilities compared with vaginal delivery. The authors speculated that neuraxial anesthesia may reduce stress responses to delivery, which could affect subsequent neurodevelopmental outcomes. To further explore this possibility, we examined the association between the use of neuraxial labor analgesia and development of childhood learning disabilities in a population-based birth cohort of children delivered vaginally. METHODS: The educational and medical records of all children born to mothers residing in the area of 5 townships of Olmsted County, Minnesota from 1976 to 1982 and remaining in the community at age 5 years were reviewed to identify those with learning disabilities. Cox proportional hazards regression was used to compare the incidence of learning disabilities between children delivered vaginally with and without neuraxial labor analgesia, including analyses adjusted for factors of either potential clinical relevance or that differed between the 2 groups in univariate analysis. RESULTS: Of the study cohort, 4684 mothers delivered children vaginally, with 1495 receiving neuraxial labor analgesia. The presence of childhood learning disabilities in the cohort was not associated with use of labor neuraxial analgesia (adjusted hazard ratio, 1.05; 95%confidence interval, 0.85-1.31; P = 0.63). CONCLUSION: The use of neuraxial analgesia during labor and vaginal delivery was not independently associated with learning disabilities diagnosed before age 19 years. Future studies are needed to evaluate potential mechanisms of the previous finding indicating that the incidence of learning disabilities is lower in children born to mothers via cesarean delivery under neuraxial anesthesia compared with vaginal delivery.

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.

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.

Early exposure to anesthesia and learning disabilities in a population-based birth cohort.

BACKGROUND: Anesthetic drugs administered to immature animals may cause neurohistopathologic changes and alterations in behavior. The authors studied association between anesthetic exposure before age 4 yr and the development of reading, written language, and math learning disabilities (LD). METHODS: This was a population-based, retrospective birth cohort study. The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota, from 1976 to 1982 and who remained in the community at 5 yr of age were reviewed to identify children with LD. Cox proportional hazards regression was used to calculate hazard ratios for anesthetic exposure as a predictor of LD, adjusting for gestational age at birth, sex, and birth weight. RESULTS: Of the 5,357 children in this cohort, 593 received general anesthesia before age 4 yr. Compared with those not receiving anesthesia (n = 4,764), a single exposure to anesthesia (n = 449) was not associated with an increased risk of LD (hazard ratio = 1.0; 95% confidence interval, 0.79-1.27). However, children receiving two anesthetics (n = 100) or three or more anesthetics (n = 44) were at increased risk for LD (hazard ratio = 1.59; 95% confidence interval, 1.06-2.37, and hazard ratio = 2.60; 95% confidence interval, 1.60-4.24, respectively). The risk for LD increased with longer cumulative duration of anesthesia exposure (expressed as a continuous variable) (P = 0.016). CONCLUSION: Exposure to anesthesia was a significant risk factor for the later development of LD in children receiving multiple, but not single anesthetics. These data cannot reveal whether anesthesia itself may contribute to LD or whether the need for anesthesia is a marker for other unidentified factors that contribute to LD.

Anesthesia for cesarean delivery and learning disabilities in a population-based birth cohort.

BACKGROUND: Anesthetics administered to immature brains may cause histopathological changes and long-term behavioral abnormalities. The association between perinatal exposure to anesthetics during Cesarean delivery (CD) and development of learning disabilities (LD) was determined in a population-based birth cohort. METHODS: The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota from 1976-1982 and remaining in the community at age 5 were reviewed to identify those with LDs. Cox proportional hazards regression was used to compare rates of LD between children delivered vaginally and via CD (with general or regional anesthesia). RESULTS: Of the 5,320 children in this cohort, 497 were delivered via CD (under general anesthesia n = 193, and regional anesthesia n = 304). The incidence of LD depended on mode of delivery (P = 0.050, adjusted for sex, birth weight, gestational age, exposure to anesthesia before age 4 yr, and maternal education). LD risk was similar in children delivered by vagina or CD with general anesthesia, but was reduced in children receiving CD with regional anesthesia (hazard ratio = 0.64, 95% confidence interval 0.44 to 0.92; P = 0.017 for comparison of CD under regional anesthesia compared to vaginal delivery). CONCLUSION: Children exposed to general or regional anesthesia during CD are not more likely to develop LD compared to children delivered vaginally, suggesting that brief perinatal exposure to anesthetic drugs does not adversely affect long-term neurodevelopmental outcomes. The risk of LD may be lower in children delivered by CD whose mothers received regional anesthesia.

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.

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.

Stimulant medication treatment of target behaviors in children with autism: a population-based study.

OBJECTIVE: This study provides detailed information about stimulant medication treatment for the target symptoms of hyperactivity, impulsivity, disinhibition, and inattention in children with autism. METHODS: In a previous study, 124 subjects fulfilling DSM-IV-based research criteria for autistic disorder were identified among all 0-21 year old residents of Olmsted County, MN from 1976-1997. For each of these 124 children with research-identified autism, information was abstracted on all prescribed psychopharmacological medications. RESULTS: Psychostimulants were used to treat 52.4% (N = 65) of the 124 subjects. The median total duration of psychostimulant treatment was 4.0 years. There were 398 episodes of psychostimulant treatment. Favorable responses were associated with 69.4% of treatment episodes. Of the 398 episodes of stimulant treatment, 16.8% were associated with a documented side effect. At least one side effect was experienced by 66% of the children. CONCLUSION: These results indicate that psychostimulants are commonly prescribed for children with autism, and suggest that these medications may improve the target symptoms of hyperactivity, impulsivity, disinhibition and inattention.

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.

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.