Diverse clinical presentation of SPTBN1 variants: Complex versus primary attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) belongs to a phenotypically broad class of mental health disorders impacting social and cognitive functioning. Despite heritability estimates of 77%-88% and a global prevalence of up to 1 in 20 children, most of the underlying genetic etiology of the disorder remains undiscovered, making it challenging to obtain a clinical molecular genetic diagnosis and to develop new treatments (Biological Psychiatry, 2005, 57, 1313; Psychological Bulletin, 2009, 135, 608; Psychological Medicine, 2014, 44, 2223). Here we report the identification of a novel ultra-rare heterozygous loss-of-function (p.Q1625*) variant in a child with complex ADHD (i.e., comorbid mild intellectual disability [ID]) and a missense (p.G1748R) variant (allele frequency of 4.7 × 10-5) in a child with primary ADHD (i.e., absence of comorbid autism spectrum disorder [ASD], ID, or syndromic features) both in the SPTBN1 gene. Missense variants in SPTBN1 have been reported in individuals with developmental disorders, language and communication disorders, and motor delays in recent publications (Nature Genetics, 2021, 53, 1006; American Journal of Medical Genetics Part A, 2021, 185, 2037) and ClinVar, though most variants in ClinVar have uncertain disease associations. The functional impact of these 135 variants, including from the current study, were further assessed using prediction scores from the recently developed AlphaMissense tool and benchmarked against published functional studies on a subset of the variants. While heterozygous SPTBN1 variants have recently been associated with neurodevelopmental disorders characterized by global developmental delay, intellectual disability, and behavioral abnormalities, the two patients in the current study expand the phenotypic spectrum to include ADHD in the absence of more severe neurodevelopmental disorders, such as ASD and moderate to severe ID. Furthermore, the culmination of these data with existing reported cases suggests that variation including loss of function and missense events underlie a broader clinical spectrum than previously understood.

Co-occurring conditions in Down syndrome: Findings from a clinical database.

Individuals with Down syndrome (DS) experience a range of medical and neurodevelopmental conditions, necessitating systematic study of their occurrence and impact on neurodevelopmental outcomes. We describe the prevalence and relationships of medical, neurodevelopmental (ND), and mental health (MH) conditions in children with DS. We created a prospective clinical database of individuals with DS, integrated into the workflow of a specialty Down Syndrome Program at a specialty pediatric referral hospital. Conditions were collected through caregiver- and clinician report at clinical visits (N = 599). We calculated frequencies of medical, ND, and MH conditions and then assessed the relationship between medical, ND, and MH conditions using frequencies and comparative statistics. The most frequent co-occurring conditions were vision (72.5%), ear/hearing (71.0%), gastrointestinal (61.3%), respiratory (45.6%), and feeding (33.6%) problems, with variation in frequency by age. ND and MH conditions were reported in one quarter, most commonly autism spectrum disorder and attention-deficit/hyperactivity disorder. Those with ND and MH conditions had greater frequency of medical conditions, with highest rates of vision, ear/hearing, and gastrointestinal issues, and CHD. Systematically collected clinical data in a large cohort of children with DS reveals high prevalence of several co-occurring medical, ND, and MH conditions. Clinical care requires an understanding of the complex relationship between medical conditions and neurodevelopment.

Adverse Effects of α-2 Adrenergic Agonists and Stimulants in Preschool-age Attention-deficit/Hyperactivity Disorder: A Developmental-Behavioral Pediatrics Research Network Study.

OBJECTIVES: To characterize and compare the type and frequency of a range of common and uncommon adverse effects (AEs) associated with α-2 adrenergic agonist (A2A) and stimulant treatment of attention-deficit/hyperactivity disorder at preschool-age as well as to evaluate the impact of age on common AEs. STUDY DESIGN: This was a retrospective electronic medical record review of children <72 months of age (n = 497) evaluated at outpatient developmental-behavioral pediatric practices at 7 US academic medical centers within the Developmental-Behavioral Pediatrics Research Network. Data on AEs were abstracted for children who had treatment initiated by a developmental-behavioral pediatrician with an A2A or stimulant medication between January 2013 and July 2017; follow-up was complete by February 2019. RESULTS: A2A and stimulants had distinctive AE profiles. A2A compared with stimulants had a greater proportion with daytime sleepiness and headaches; stimulants had significantly greater proportions for most other AE, including moodiness/irritability, difficulty with sleep, appetite suppression, stomachaches, skin picking/repetitive behaviors, withdrawn behavior, and weight loss. Younger age was associated with disruptive behavior and difficulty with sleep. CONCLUSIONS: Stimulants had a greater rate of most AEs compared with A2A. AE profiles, together with efficacy, should inform clinical decision-making. Prospective randomized clinical trials are needed to fully compare efficacy and AE profiles of A2A and stimulants.

Development and implementation of a longitudinal clinical database for down syndrome in a large pediatric specialty clinic: Methodology and feasibility.

Down syndrome (DS) is a complex condition associated with multiple medical, developmental, and behavioral concerns. A prospective, longitudinal clinical database was integrated into a specialty Down Syndrome Program, with the goals of better understanding the incidence, course, and impact of co-occurring medical, neurodevelopmental, and mental health conditions in DS. We describe the process of developing the database, including a systematic approach to data collection and database infrastructure, and report on feasibility, challenges, and solutions of initial implementation. Between March 2018 and November 2021, data from 842 patients (ages 4.8 months to 26 years) was collected. Challenges included caregiver form completion as well as time and personnel required for successful implementation. With full integration into clinical visit flow, the database proved to be feasible. The database enables identification of patterns of development and health throughout the lifespan and it facilitates future data sharing and collaborative research to advance care.

Is it feasible to assess self-reported quality of life in individuals who are deaf and have intellectual disabilities?

PURPOSE: There is consensus that Quality of Life (QOL) should be obtained through self-reports from people with intellectual Disability (ID). Thus far, there have been no attempts to collect self-reported QOL from people who are deaf and have ID. METHODS: Based on an established short measure for QOL (EUROHIS-QOL), an adapted easy-to-understand sign language interview was developed and applied in a population (n = 61) with severe-to-profound hearing loss and mild-to-profound ID. Self-reports were conducted at two time points (t1 and t2), 6 months apart. The Stark QOL, an established picture-based questionnaire, was also obtained at t2 and three Proxy ratings of QOL (from caregivers) were conducted for each participant at t1. RESULTS: Self-reported QOL was successfully administered at both time points for 44 individuals with mild and moderate ID (IQ reference age between 3.3 and 11.8 years). The self-reports showed sufficient test-retest reliability and significant correlations with the Stark QOL. As anticipated, self-reported QOL was higher than proxy-reported QOL. Test-retest reliability and internal consistency were good for self-reported QOL. CONCLUSION: Reliable and valid self-reports of QOL can be obtained from deaf adults with mild-moderate ID using standard inventories adapted to the linguistic and cognitive level of these individuals.

α2-Adrenergic Agonists or Stimulants for Preschool-Age Children With Attention-Deficit/Hyperactivity Disorder.

Importance: Attention-deficit/hyperactivity disorder (ADHD) is diagnosed in approximately 2.4% of preschool-age children. Stimulants are recommended as first-line medication treatment. However, up to 25% of preschool-age children with ADHD are treated with α2-adrenergic agonist medications, despite minimal evidence about their efficacy or adverse effects in this age range. Objective: To determine the frequency of reported improvement in ADHD symptoms and adverse effects associated with α2-adrenergic agonists and stimulant medication for initial ADHD medication treatment in preschool-age children. Design, Setting, and Participants: Retrospective electronic health record review. Data were obtained from health records of children seen at 7 outpatient developmental-behavioral pediatric practices in the Developmental Behavioral Pediatrics Research Network in the US. Data were abstracted for 497 consecutive children who were younger than 72 months when treatment with an α2-adrenergic agonist or stimulant medication was initiated by a developmental-behavioral pediatrician for ADHD and were treated between January 1, 2013, and July 1, 2017. Follow-up was complete on February 27, 2019. Exposures: α2-Adrenergic agonist vs stimulant medication as initial ADHD medication treatment. Main Outcomes and Measures: Reported improvement in ADHD symptoms and adverse effects. Results: Data were abstracted from electronic health records of 497 preschool-age children with ADHD receiving α2-adrenergic agonists or stimulants. Median child age was 62 months at ADHD medication initiation, and 409 children (82%) were males. For initial ADHD medication treatment, α2-adrenergic agonists were prescribed to 175 children (35%; median length of α2-adrenergic agonist use, 136 days) and stimulants were prescribed to 322 children (65%; median length of stimulant use, 133 days). Improvement was reported in 66% (95% CI, 57.5%-73.9%) of children who initiated α2-adrenergic agonists and 78% (95% CI, 72.4%-83.4%) of children who initiated stimulants. Only daytime sleepiness was more common for those receiving α2-adrenergic agonists vs stimulants (38% vs 3%); several adverse effects were reported more commonly for those receiving stimulants vs α2-adrenergic agonists, including moodiness/irritability (50% vs 29%), appetite suppression (38% vs 7%), and difficulty sleeping (21% vs 11%). Conclusions and Relevance: In this retrospective review of health records of preschool-age children with ADHD treated in developmental-behavioral pediatric practices, improvement was noted in the majority of children who received α2-adrenergic agonists or stimulants, with differing adverse effect profiles between medication classes. Further research, including from randomized clinical trials, is needed to assess comparative effectiveness of α2-adrenergic agonists vs stimulants.

Topical Review: Transitional Services for Teens and Young Adults With Attention-Deficit Hyperactivity Disorder: A Process Map and Proposed Model to Overcoming Barriers to Care.

Objective: To provide a topical review of the personal vulnerabilities and systemic barriers facing transitional age young adults with attention-deficit hyperactivity disorder (ADHD), followed by a proposed model for overcoming those barriers. Methods: Drawing from a growing, but limited, literature on the topic, we outline a process map for identifying and troubleshooting barriers to care in this at-risk population. Results: Young adults with ADHD frequently lack the organizational skills, time management, prioritization, and persistence to manage their health care at an expected level of adult independence. These difficulties are compounded by a health-care system that has less time or fewer resources for supporting young adult patients. Conclusions: Recommendations for easing the transition from pediatric to adult care for late adolescents with ADHD include heavily leveraging the doctor-patient relationship, and capturing the young adult's attention through technologies that already absorb them.

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.

Persistence of Autism Spectrum Disorder From Early Childhood Through School Age.

Importance: While the prevalence of autism spectrum disorder (ASD) continues to increase and early diagnosis is emphasized, there is limited information on outcomes for children diagnosed with ASD in early childhood using contemporary diagnostic criteria. Objectives: To determine the frequency with which children who are clinically diagnosed with ASD at 12 to 36 months of age continue to meet diagnostic criteria for ASD at 5 to 7 years of age and to evaluate whether baseline child-specific and demographic characteristics and receipt of interventions are associated with ASD persistence. Design, Setting, and Participants: In this natural history cohort study, children who received a clinical ASD diagnosis at 12 to 36 months of age underwent a research diagnostic assessment at 5 to 7 years of age. Research assessments occurred from August 14, 2018, to January 8, 2022. Intervention: Children received community-based interventions, and parents provided details about interventions received. Main Outcomes and Measures: The main outcome was persistence of ASD diagnosis based on current functioning. An experienced research psychologist assigned an ASD diagnosis (present or absent) according to criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) after the research assessment. The research assessment included administration of the Autism Diagnostic Observation Schedule-2, Autism Diagnostic Interview-Research, and a cognitive measure. Results: Of the 213 participants diagnosed with ASD at initial clinical assessment (mean [SD] age, 24.6 [3.9] months; 177 boys [83.1%]), 79 (37.1%) did not continue to meet diagnostic criteria for ASD (nonpersistent ASD) at research assessment (mean [SD] age, 74.3 [7.1] months). All children with nonpersistent ASD had IQ of at least 70, while there was a bimodal distribution of IQ for those with persistent ASD (46 with IQ <70 and 88 with IQ ≥70). All children received some interventions, and 201 (94.4%) received ASD-specific intervention, mostly applied behavioral analysis. In a multilevel logistic regression model, the only variables associated with increased odds of being in the nonpersistent ASD group at 6 years of age were higher baseline adaptive skills (b coefficient = -0.287 [SE, 0.108]) and female sex (b = 0.239 [SE, 0.064]). Conclusions and Relevance: The findings of this cohort study suggest that among toddlers diagnosed with ASD, baseline adaptive function and sex may be associated with persistence of ASD.

Do Externalizing and Internalizing Symptoms Moderate Medication Response in Preschool Attention-Deficit/Hyperactivity Disorder? A DBPNet Study.

OBJECTIVES: This study aimed to determine whether parent ratings of attention-deficit/hyperactivity disorder (ADHD) symptom severity or externalizing symptoms (EXT) or internalizing symptoms (INT) moderate response to stimulants (STIM) and alpha-2 adrenergic agonists (A2As) in preschool ADHD. METHODS: Health records for children treated with medication for ADHD and with parent rating scale data available (N = 309; age <72 months) were reviewed at 7 Developmental-Behavioral Pediatric Research Network sites. Severity of ADHD was defined as the number of ADHD symptoms occurring often or very often on DSM-IV-based parent rating scales. EXT or INT from standardized rating scales were categorized as T score <60, 60 to <70, or ≥70. Ordinal logistic regression models predicting response to medication were calculated. RESULTS: The median (interquartile range) age at ADHD diagnosis was 59 (54-65) months. One hundred eighty-three participants had ADHD symptom severity, and 195 had EXT or INT data. ADHD severity was not associated with medication response. Both EXT and INT were associated with medication response but with significant medication class by EXT/INT interactions. Children with higher EXT were less likely to respond to STIM, with percentage of nonresponders for T-score categories <60, 60 to <70, and ≥70 being 3.6%, 25.7%, and 33.3% (p = 0.016) and, for A2As, being 60%, 50%, and 33.3% (p = 0.55), respectively. A similar pattern was observed for INT categories: STIM 19.4%, 22.5%, and 50.0% (p = 0.002) and A2As 42.3%, 30%, and 42.3% (p = 0.48), respectively. CONCLUSION: For preschool ADHD, low ratings of EXT or INT are associated with a high likelihood of response to STIM. By contrast, response rates to STIM and A2As are more similar for children with high levels of EXT or INT.

Receipt of Behavioral Therapy in Preschool-Age Children with ADHD and Coexisting Conditions: A DBPNet Study.

OBJECTIVE: Practice guidelines from the American Academy of Pediatrics and Society for Developmental and Behavioral Pediatrics recommend evidence-based behavioral therapy (BT) as first-line treatment for preschool-age children with ADHD, prior to medication initiation. Thus, this study's objective is to present the frequency of physician-documented receipt of BT in preschool-age children with ADHD prior to medication initiation and to determine factors associated with receipt BT receipt. METHODS: This retrospective medical record review was conducted across 7 Developmental Behavioral Pediatrics Research Network (DBPNet) sites. Data were abstracted for children <72 months old seen by a DBP clinician and initiated on ADHD medication between 1/1/2013-7/1/2017. From narrative text of the medical records, BT receipt was coded as: parent training in behavior management (PTBM), Applied Behavior Analysis (ABA), other, or did not receive. RESULTS: Of the 497 children in this study; 225 children (45%) had reported receipt of any BT prior to ADHD medication initiation, with 15.9% (n = 79) receiving PTBM. Children with co-existing diagnoses of ASD or disruptive behavior disorder were more likely to receive BT than children without co-existing conditions (59.3% vs 69.0% vs 30.6%). There was significant site variability in reported receipt of BT, ranging from 22.4% to 74.1%, and sex and insurance were not associated with BT rates. CONCLUSION: The percentage of children with documented receipt of any BT, and particularly PTBM, was low across all sites and co-existing conditions. These findings highlight the universal need to increase receipt of evidence-based BT for all young children with ADHD.

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.

Description of Clinician-Diagnosed Regression at Time of Autism Spectrum Disorder Diagnosis in Toddlers.

OBJECTIVE: Previous studies have reported varying rates of regression in children with autism spectrum disorder (ASD). We sought to (1) determine the rate of clinician-diagnosed regression for young children with ASD and (2) compare developmental functioning and ASD symptoms of children with versus without regression. METHODS: We conducted a retrospective chart review of toddlers (age 18-36 months) with Diagnostic and Statistical Manual-5 ASD. We abstracted cognitive, language, adaptive, and motor functioning standard scores and ASD core symptoms. Regression was defined as "clinician-diagnosed regression accompanied by recommendation for a medical workup." We used propensity scores to match each participant with regression (n = 20) one-to-one with a participant without regression (n = 20). We compared the groups on developmental scores using independent sample t tests and on core ASD symptoms using Pearson's χ 2 test. RESULTS: Of the 500 children with ASD, n = 20 (4%) had regression (defined above). Children with regression had lower Bayley cognitive and language scores and lower Vineland adaptive scores compared with those without regression (cognitive: 78.0 vs 85.5, p < 0.05; language: 56.9 vs 68.2, p < 0.01; adaptive: 70.0 vs 80.3; p < 0.01). There was no difference in motor scores across groups. There were no significant differences in the frequency of exhibiting core ASD symptoms for those with versus without regression. CONCLUSION: In this clinical sample of children with ASD, regression was diagnosed in a small percentage (4%). Those with regression had lower cognitive, language, and adaptive skills compared with those without regression. Rates of clinician-diagnosed regression referred for medical workup are significantly lower than prior estimates based on parent report.

Male and Female Toddlers with DSM-5 Autism Spectrum Disorder have Similar Developmental Profiles and Core Autism Symptoms.

Compare developmental profiles and core ASD symptom manifestation between male and female toddlers with DSM-5 ASD. Retrospective record review of 500 toddlers (79% male) at time of ASD diagnosis. There were no differences in developmental functioning between males and females. When adjusting for multiple comparisons, sex differences were only noted for sensory seeking behavior occurring at a higher frequency in females. Overall, there were no significant differences in demographic characteristics, developmental functioning, or manifestation of core ASD symptoms between males versus female toddlers at the time of DSM-5 ASD diagnosis.

Recalled Experiences of Bullying and Victimization in a Longitudinal, Population-Based Birth Cohort: The Influence of ADHD and Co-Occurring Psychiatric Disorder.

OBJECTIVE: To describe bullying experiences throughout childhood of people with and without childhood ADHD and co-occurring learning and psychiatric disorders from a population-based birth cohort. METHODS: In a secondary data analysis of 199 childhood ADHD cases and 287 non-ADHD referents (N = 486), reported experiences of peer interactions during elementary, middle, or high school were classified as "bully," "victim," "neither," or "both." Associations were assessed with multinomial logistic regression. RESULTS: Adjusted for male sex, the odds of classification as victim-only, victim/bully, or bully- only (vs. neither) were 3.70 (2.36-5.81), 17.71, and 8.17 times higher for childhood ADHD cases compared to non-ADHD referents. Victim-bullies (62.5%) and bullies (64.3%) had both childhood ADHD and other psychiatric disorders versus 38.4% of victims-only and 17.3% of those classified as "neither." CONCLUSION: The list of serious lifetime consequences of having ADHD also includes bullying. We offer future research directions for determining potential causal pathways.

Children With ADHD Are at Risk for a Broad Array of Adverse Adult Outcomes That Cross Functional Domains: Results From a Population-Based Birth Cohort Study.

OBJECTIVE: To identify patterns ("classes") of outcomes for adults with and without childhood ADHD. METHOD: Subjects were 232 childhood ADHD cases and 335 non-ADHD referents from a 1976 to 1982 birth cohort. We used latent class analyses to identify classes based on a broad array of adult psychosocial outcomes and determined the proportion of subjects with childhood ADHD within each class. RESULTS: A three class solution provided optimal model fit; classes were termed "good," "intermediate," and "poor" functioning. Subjects with childhood ADHD comprised 62.8% of the "poor," 53.5% of the "intermediate," and 24.9% of the "good" functioning class. The "poor" functioning class was distinguished by increased likelihood of legal trouble and substance use disorders and included more individuals with childhood ADHD and psychiatric disorder than the "intermediate" class (45.5% vs. 30.6%). CONCLUSION: Children with ADHD are at risk for adverse adult outcomes in multiple domains and co-morbid childhood psychiatric disorders increase risk.

Clinician Diagnostic Certainty and the Role of the Autism Diagnostic Observation Schedule in Autism Spectrum Disorder Diagnosis in Young Children.

Importance: Autism spectrum disorder (ASD) affects 1 in 44 children. The Autism Diagnostic Observation Schedule (ADOS) is a semi-structured observation developed for use in research but is considered a component of gold standard clinical diagnosis. The ADOS adds time and cost to diagnostic assessments. Objective: To evaluate consistency between clinical diagnosis (index ASD diagnosis) and diagnosis incorporating the ADOS (reference standard ASD diagnosis) and to examine clinician and child factors that predict consistency between index diagnoses and reference standard diagnoses. Design, Setting, and Participants: This prospective diagnostic study was conducted between May 2019 and February 2020. Developmental-behavioral pediatricians (DBPs) made a diagnosis based on clinical assessment (index ASD diagnosis). The ADOS was then administered, after which the DBP made a second diagnosis (reference standard ASD diagnosis). DBPs self-reported diagnostic certainty at the time of the index diagnoses and reference standard diagnoses. The study took place at 8 sites (7 US and 1 European) that provided subspecialty assessments for children with concerns for ASD. Participants included children aged 18 months to 5 years, 11 months, without a prior ASD diagnosis, consecutively referred for possible ASD. Among 648 eligible children, 23 refused, 376 enrolled, and 349 completed the study. All 40 eligible DBPs participated. Exposures: ADOS administered to all child participants. Main Outcomes and Measures: Index diagnoses and reference standard diagnoses of ASD (yes/no). Results: Among the 349 children (279 [79.7%] male; mean [SD] age, 39.9 [13.4] months), index diagnoses and reference standard diagnoses were consistent for 314 (90%) (ASD = 250; not ASD = 64) and changed for 35. Clinician diagnostic certainty was the most sensitive and specific predictor of diagnostic consistency (area under curve = 0.860; P < .001). In a multilevel logistic regression, no child or clinician factors improved prediction of diagnostic consistency based solely on clinician diagnostic certainty at time of index diagnosis. Conclusions and Relevance: In this prospective diagnostic study, clinical diagnoses of ASD by DBPs with vs without the ADOS were consistent in 90.0% of cases. Clinician diagnostic certainty predicted consistency of index diagnoses and reference standard diagnoses. This study suggests that the ADOS is generally not required for diagnosis of ASD in young children by DBPs and that DBPs can identify children for whom the ADOS may be needed.

Association of Coexisting Conditions, Attention-Deficit/Hyperactivity Disorder Medication Choice, and Likelihood of Improvement in Preschool-Age Children: A Developmental Behavioral Pediatrics Research Network Study.

Objectives: To determine whether conditions coexisting with attention-deficit/hyperactivity disorder (ADHD) in preschool-age children are associated with choice of stimulants or alpha-2 adrenergic agonists (A2As) and/or likelihood of improvement in ADHD symptoms. Methods: A retrospective electronic health record review of 497 children from 7 Developmental Behavioral Pediatrics Research Network (DBPNet) sites. Children were <72 months when treated with medication for ADHD from January 1, 2013 to July 1, 2017. We abstracted coexisting conditions, initial medication prescribed, and whether the medication was associated with improvement in symptoms. Analysis of improvement was adjusted for clustering by clinician and site. Results: The median (interquartile range) child age at the time of initiation of ADHD medication was 62 (54-67) months. The most common coexisting conditions included language disorders (40%), sleep disorders (28%), disruptive behavior disorders (22.7%), autism spectrum disorder (ASD; 21.8%), and motor disorders (19.9%). No coexisting conditions were present in 17.1%; 1 in 36.8%, 2 in 26.8%, and ≥3 in 19.3%. Stimulants were initially prescribed for 322 (64.8%) and A2A for 175 (35.2%) children. Children prescribed stimulants were more likely to have no coexisting conditions than those prescribed A2A (22.3% vs. 7.4%; p < 0.001). Coexisting ASD and sleep disorder were associated with increased likelihood of starting A2As versus stimulants (p < 0.0005; p = 0.002). The association between medication treatment and improvement varied by number of coexisting conditions for 0, 1, 2, or ≥3, respectively (84.7%, 73.8%, 72.9%, 64.6%; p = 0.031). Children with ≥3 coexisting conditions were less likely to respond to stimulants than children with no coexisting conditions (67.4% vs. 79.9%; p = 0.037). Conclusions: Among preschool-age children with ADHD, those with ≥3 coexisting conditions were less likely to respond to stimulants than those with no coexisting conditions. This was not found for A2A, but further research is needed as very few children with no coexisting conditions were treated with A2A.

Language Screening in 3-Year-Olds: Development and Validation of a Feasible and Effective Instrument for Pediatric Primary Care.

Objective: The study was aimed at evaluating the validity and feasibility of SPES-3 (Sprachentwicklungsscreening), a language screening in 3-year-old children within the constraints of regular preventive medical check-ups. Methods: A four-component screening measure including parental reports on the child's expressive vocabulary and grammar based on the MacArthur Communicative Development Inventory and pediatrician-administered standardized assessments of noun plurals and sentence comprehension was used in a sample of 2,044 consecutively seen children in 30 pediatric offices. One-hundred forty-four children (70 who failed and 74 who passed the screener) comprised the validation sample and also underwent follow-up gold standard assessment. To avoid verification and spectrum bias multiple imputation of missing diagnosis for children who did not undergo gold standard assessment was used. Independent diagnoses by two experts blinded to the screening results were considered gold standard for diagnosing language disorder. Screening accuracy of each of the four subscales was analyzed using receiver operator characteristic (ROC) curves. Feasibility was assessed by use of a questionnaire completed by the pediatricians. Results: The two parental screening subscales demonstrated excellent accuracy with area under the curve (AUC) scores of 0.910 and 0.908 whereas AUC scores were significantly lower for the subscales directly administered by the pediatricians (0.816 and 0.705). A composite score based on both parental screening scales (AUC = 0.946) outperformed single subscales. A cut off of 41.69 on a T-scale resulted in about 20% positive screens and showed good sensitivity (0.878) and specificity (0.876). Practicability, acceptability and sustainability of the screening measure were mostly rated as high. Conclusion: The parent-reported subscales of the SPES-3 language screener are a promising screening tool for use in primary pediatric care settings.

Identifying Subgroups of Toddlers with DSM-5 Autism Spectrum Disorder Based on Core Symptoms.

The objective of this study was to identify subgroups of toddlers with DSM-5 ASD based on core ASD symptoms using a person-based analytical framework. This is a retrospective study of 500 toddlers (mean age 26 months, 79% male) with DSM-5 ASD. Data were analyzed using latent class analyses in which profiles were formed based on ASD symptomatology. Social communication (SC) symptoms favored a three-class solution, while restricted/repetitive behaviors (RRBs) favored a two-class solution. Classes with higher consistency of SC deficits were younger, with lower developmental functioning. The class with more RRBs was older, with higher functioning. If confirmed in other populations, these classes may more precisely characterize subgroups within the heterogeneous group of toddlers at time of ASD diagnosis.