The aim of this study was to compare differences in cognitive, adaptive, and language function in young children referred for concerns for autism spectrum disorder (ASD) who are diagnosed with ASD vs those not diagnosed with ASD (no ASD). This prospective diagnostic study of 349 children < 6 years of age, with 250 diagnosed with ASD and 99 with no ASD, was conducted at 8 diagnostic centers. There were no differences in cognition between those diagnosed with ASD and those with no ASD. As compared to those with no ASD, children with ASD had significantly lower language and adaptive functioning. Children with no ASD had language and adaptive functioning similar to their cognitive function. Differences between developmental domains were also compared within the ASD and no ASD groups. There were no differences between any 2 areas of function in the no ASD group. However, there were significant differences within the ASD group, with cognitive function significantly higher than both language function and adaptive function. This study suggests that a discrepancy between adaptive and language skills beyond that expected based on cognitive function should heighten concern for ASD. Beyond the categorical diagnosis of ASD, it is important to assess all these developmental domains to develop comprehensive plans for interventions.

OBJECTIVE:The aim of this study is to identify characteristics of children for whom a developmental-behavioral pediatrician's (DBP) diagnostic impressions of autism spectrum disorder (ASD) or non-ASD were changed by Autism Diagnostic Observation Schedule (ADOS) results. METHOD:A prospective study of children 1½ to <6 years consecutively referred to 8 sites for possible ASD. Cognitive/developmental, language, and adaptive testing varied, as each site followed its usual clinical approach. DBPs documented diagnosis as ASD or non-ASD and their degree of diagnostic certainty (1-10) pre- and post-ADOS. Cases where DBP diagnostic impression did not change after ADOS administration ("Stable Group," n = 314) were compared with those for whom it did change ("Changed Group," n = 35), followed by matched random sample comparisons. RESULTS:There were no significant differences in child characteristics (age, gender, race, ethnicity, insurance, caregiver education) between the Stable and Changed groups. DBPs' diagnostic certainty was significantly lower, both pre- and post-ADOS, in the Changed versus Stable group. Change was associated with milder symptoms of ASD and less impaired language. In an age- and gender-matched comparison, significant differences remained for diagnostic certainty and severity of social communication impairments. Cognitive scores were significantly higher in the Changed Group. Because of significantly higher caregiver education and a trend toward more privately insured children among the Changed Group, samples (n = 35 each) were then matched on those characteristics, revealing the same differences for diagnostic certainty, severity of ASD symptoms, and language skills. CONCLUSION:Young children with milder ASD symptoms and less impaired language may benefit most from the administration of the ADOS.

Developmental–behavioral pediatrics (DBP) subspecialists care for children with complex neurodevelopmental and behavioral health conditions; additional roles include education and training, advocacy, and research. In 2023, there were 1.0 DBP subspecialists per 100 000 US children aged 0 to 17 years (range 0.0–3.8), with wide variability in DBP subspecialist distribution. Given the prevalence of DB conditions, the current workforce is markedly inadequate to meet the needs of patients and families. The American Board of Pediatrics Foundation led a modeling project to forecast the US pediatric subspecialty workforce from 2020 to 2040 using current trends in each subspecialty. The model predicts workforce supply at baseline and across alternative scenarios and reports results in headcount (HC) and HC adjusted for percent time spent in clinical care, termed “clinical workforce equivalent.” For DBP, the baseline model predicts HC growth nationally (+45%, from 669 to 958), but these extremely low numbers translate to minimal patient care impact. Adjusting for population growth over time, projected HC increases from 0.8 to 1.0 and clinical workforce equivalent from 0.5 to 0.6 DBP subspecialists per 100 000 children aged 0 to 18 years by 2040. Even in the best-case scenario (+12.5% in fellows by 2030 and +7% in time in clinical care), the overall numbers would be minimally affected. These current and forecasted trends should be used to shape much-needed solutions in education, training, practice, policy, and workforce research to increase the DBP workforce and improve overall child health.

OBJECTIVE: To determine the proportion of children referred to academic medical centers with concerns about autism spectrum disorders (ASDs) who received a probable ASD diagnosis, identify factors predicting ASD diagnosis, and describe the children with ASD concerns who were not found to have autism. METHODS: A total of 55 developmental-behavioral pediatricians (DBP) at 12 academic sites in the DBPNet research network recorded data on <= 15 consecutive new patients. They coded presumed diagnoses after their first visit with the child. RESULTS: Of 784 new visits, 324 (41%) had concern for ASD; of these, 221 (68%) were presumptively ASD+; 103 (32%) were ASD-. In a mixed model accounting for clustering within site and covariates significant in bivariate analysis, significant predictors of receiving a presumptive ASD diagnoses were socialization concerns, languages other than English spoken in the home, and coming for second opinion. Also concern for "other behavior problems" (not mood, oppositionality, anxiety, attention, or repetitive behaviors) predicted not receiving ASD diagnoses. This model was not clinically useful because it misclassified 26.9% of children. ASD- children <4 years old had more language delay and less cognitive impairment and socialization concern than their ASD+ age peers. ASD- children >= 4 years old were more likely to have attention-deficit /hyperactivity disorder (ADHD) and learning disability with normal cognition than their ASD+ age peers. CONCLUSIONS: Two thirds of children referred to academic centers with concern for ASD received a presumptive diagnosis of ASD. While those with ASD were not easily distinguished from those without ASD at referral, virtually all children with ASD concerns had multiple DBP diagnoses made and required DBP follow-up care.

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.

Review international efforts to build a global public health initiative focused on toxoplasmosis with spillover benefits to save lives, sight, cognition and motor function benefiting maternal and child health. Multiple countries’ efforts to eliminate toxoplasmosis demonstrate progress and context for this review and new work. Problems with potential solutions proposed include accessibility of accurate, inexpensive diagnostic testing, pre-natal screening and facilitating tools, missed and delayed neonatal diagnosis, restricted access, high costs, delays in obtaining medicines emergently, delayed insurance pre-approvals and high medicare copays taking considerable physician time and effort, harmful shortcuts being taken in methods to prepare medicines in settings where access is restricted, reluctance to perform ventriculoperitoneal shunts promptly when needed without recognition of potential benefit, access to resources for care, especially for marginalized populations, and limited use of recent advances in management of neurologic and retinal disease which can lead to good outcomes.

Purpose of Review Review work to create and evaluate educational materials that could serve as a primary prevention strategy to help both providers and patients in Panama, Colombia, and the USA reduce disease burden of Toxoplasma infections. Recent Findings Educational programs had not been evaluated for efficacy in Panama, USA, or Colombia. Summary Educational programs for high school students, pregnant women, medical students and professionals, scientists, and lay personnel were created. In most settings, short-term effects were evaluated. In Panama, Colombia, and USA, all materials showed short-term utility in transmitting information to learners. These educational materials can serve as a component of larger public health programs to lower disease burden from congenital toxoplasmosis. Future priorities include conducting robust longitudinal studies of whether education correlates with reduced adverse disease outcomes, modifying educational materials as new information regarding region-specific risk factors is discovered, and ensuring materials are widely accessible.

Review building of programs to eliminate Toxoplasma infections. Morbidity and mortality from toxoplasmosis led to programs in USA, Panama, and Colombia to facilitate understanding, treatment, prevention, and regional resources, incorporating student work. Studies foundational for building recent, regional approaches/programs are reviewed. Introduction provides an overview/review of programs in Panamá, the United States, and other countries. High prevalence/risk of exposure led to laws mandating testing in gestation, reporting, and development of broad-based teaching materials about Toxoplasma. These were tested for efficacy as learning tools for high-school students, pregnant women, medical students, physicians, scientists, public health officials and general public. Digitized, free, smart phone application effectively taught pregnant women about toxoplasmosis prevention. Perinatal infection care programs, identifying true regional risk factors, and point-of-care gestational screening facilitate prevention and care. When implemented fully across all demographics, such programs present opportunities to save lives, sight, and cognition with considerable spillover benefits for individuals and societies.

Background Down syndrome is a chromosomal disorder with considerable neurodevelopmental impact and neurodegenerative morbidity. In a pilot trial in young adults with Down syndrome, memantine (a drug approved for Alzheimer's disease) showed a significant effect on a secondary measure of episodic memory. We aimed to test whether memantine would improve episodic memory in adolescents and young adults with Down syndrome. Methods We did a randomised, double-blind, placebo-controlled phase 2 trial with a parallel design, stratified by age and sex. Participants (aged 15-32 years) with either trisomy 21 or complete unbalanced translocation of chromosome 21 and in general good health were recruited from the community at one site in Brazil and another in the USA. Participants were randomly assigned (1:1) to receive either memantine (20 mg/day orally) or placebo for 16 weeks. Computer-generated randomisation tables for both sites (allocating a placebo or drug label to each member of a unique pair of participants) were centrally produced by an independent statistician and were shared only with investigational pharmacists at participating sites until unblinding of the study. Participants and investigators were masked to treatment assignments. Neuropsychological assessments were done at baseline (T1) and week 16 (T2). The primary outcome measure was change from baseline to week 16 in the California Verbal Learning Test-second edition short-form (CVLT-II-sf) total free recall score, assessed in the per-protocol population (ie, participants who completed 16 weeks of treatment and had neuropsychological assessments at T1 and T2). Linear mixed effect models were fit to data from the per-protocol population. Safety and tolerability were monitored and analysed in all participants who started treatment. Steady-state concentrations in plasma of memantine were measured at the end of the trial. This study is registered at ClinicalTrials.gov, number NCT02304302. Findings From May 13, 2015, to July 22, 2020, 185 participants with Down syndrome were assessed for eligibility and 160 (86%) were randomly assigned either memantine (n=81) or placebo (n=79). All participants received their allocated treatment. Linear mixed effect models were fit to data from 149 (81%) participants, 73 in the memantine group and 76 in the placebo group, after 11 people (eight in the memantine group and three in the placebo group) discontinued due to COVID-19 restrictions, illness of their caregiver, adverse events, or low compliance. The primary outcome measure did not differ between groups (CVLT-II-sf total free recall score, change from baseline 0.34 points [95% CI -0.98 to 1.67], p=0.61). Memantine was well tolerated, with infrequent mild-to-moderate adverse events, the most common being viral upper respiratory infection (nine [11%] participants in the memantine group and 12 [15%] in the placebo group) and transient dizziness (eight [10%] in the memantine group and six [8%] in the placebo group). No serious adverse events were observed. Amounts of memantine in plasma were substantially lower than those considered therapeutic for Alzheimer's disease. Interpretation Memantine was well tolerated, but cognition-enhancing effects were not recorded with a 20 mg/day dose in adolescents and young adults with Down syndrome. Exploratory analyses point to a need for future work. Funding Alana Foundation. Copyright (C) 2021 Elsevier Ltd. All rights reserved.

Review comprehensive data on rates of toxoplasmosis in Panama and Colombia. Samples and data sets from Panama and Colombia, that facilitated estimates regarding seroprevalence of antibodies to Toxoplasma and risk factors, were reviewed. Screening maps, seroprevalence maps, and risk factor mathematical models were devised based on these data. Studies in Ciudad de Panamá estimated seroprevalence at between 22 and 44%. Consistent relationships were found between higher prevalence rates and factors such as poverty and proximity to water sources. Prenatal screening rates for anti-Toxoplasma antibodies were variable, despite existence of a screening law. Heat maps showed a correlation between proximity to bodies of water and overall Toxoplasma seroprevalence. Spatial epidemiological maps and mathematical models identify specific regions that could most benefit from comprehensive, preventive healthcare campaigns related to congenital toxoplasmosis and Toxoplasma infection.

OBJECTIVE:To examine and define the evolving subspecialty of developmental-behavioral pediatrics (DBP) by analyzing workforce surveys presubspecialty and postsubspecialty certification. METHODS:In 2015, an electronic workforce survey was sent to the members of the American Academy of Pediatrics Section on DBP and Council on Children with Disabilities and the Society for DBP. Answers from the 1998 survey for respondents with subspecialty fellowship training were compared. RESULTS:Compared with the 1998 group of 265 DBPs, the 368 DBPs in the 2015 group were older, more female, and more diverse. In both groups, ≥80% evaluated and treated autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and developmental delays, but significantly (p < 0.001) fewer cared for children with physical disabilities (e.g., cerebral palsy [58% to 41%], multihandicapped [53% to 39%], neonatal follow-up [47% to 31%], and spina bifida [26% to 13%]) and other disorders (e.g., failure to thrive and obesity/eating disorders [27% to 15%]). Time for new patient and return visits remained the same (1.5 hours and 0.7 hours). Pediatric generalists and family practice physicians initiated most referrals; fewer 2015 DBPs (p < 0.001) reported school districts (83% to 70%) and more reported pediatric subspecialty (57% to 77%; p < 0.001) referrals. Acknowledgment of the need for more community DBP specialists increased from 66% to 80% (p < 0.001). CONCLUSION:Survey data indicated that the workforce is aging and changing. ADHD, ASD, and developmental delays are solidifying as the defining clinical focus of DBP. Current trends can identify training needs, facilitate recruitment, and advocate for system change to support the DBP workforce to respond to the great need.

BACKGROUND: Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community. OBJECTIVE: The National Down Syndrome Society (NDSS) and the LuMind IDSC Foundation worked together with scientific and medical experts to develop recommendations for the NIH research plan. METHODS: NDSS and LuMind IDSC assembled over 50 experts across multiple disciplines and organized them in eleven working groups focused on specific issues for people with DS. RESULTS: This review article summarizes the research gaps and recommendations that have the potential to improve the health and quality of life for people with DS within the next decade. CONCLUSIONS: This review highlights many of the scientific gaps that exist in DS research. Based on these gaps, a multidisciplinary group of DS experts has made recommendations to advance DS research. This paper may also aid policymakers and the DS community to build a comprehensive national DS research strategy.