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AIM: We examined key features of two outcome measures for social dysfunction and autism spectrum disorder traits, the Social Responsiveness Scale, Second Edition (SRS-2) and the Social Skills Improvement System - Rating Scales (SSIS-RS), in children with neurofibromatosis type 1 (NF1). The aim of the study was to provide objective evidence as to which behavioural endpoint should be used in clinical trials. METHOD: Cross-sectional behavioural and demographic data were pooled from four paediatric NF1 tertiary referral centres in Australia and the United States (N=122; 65 males, 57 females; mean age [SD] 9y 2mo [3y], range 3-15y). RESULTS: Distributions of SRS-2 and SSIS-RS scores were unimodal and both yielded deficits, with a higher proportion of severely impaired scores on the SRS-2 (16.4%) compared to the SSIS-RS (8.2%). Pearson's product-moment correlations revealed that both questionnaires were highly related to each other (r=-0.72, p

Objective Rapid developments in understanding the molecular mechanisms underlying cognitive deficits in neurodevelopmental disorders have increased expectations for targeted, mechanism‐based treatments. However, translation from preclinical models to human clinical trials has proven challenging. Poor reproducibility of cognitive endpoints may provide one explanation for this finding. We examined the suitability of cognitive outcomes for clinical trials in children with neurofibromatosis type 1 (NF1) by examining test‐retest reliability of the measures and the application of data reduction techniques to improve reproducibility. Methods Data were analyzed from the STARS clinical trial (n = 146), a multi‐center double‐blind placebo‐controlled phase II trial of lovastatin, conducted by the NF Clinical Trials Consortium. Intra‐class correlation coefficients were generated between pre‐ and post‐performances (16‐week interval) on neuropsychological endpoints in the placebo group to determine test‐retest reliabilities. Confirmatory factor analysis was used to reduce data into cognitive domains and account for measurement error. Results Test‐retest reliabilities were highly variable, with most endpoints demonstrating unacceptably low reproducibility. Data reduction confirmed four distinct neuropsychological domains: executive functioning/attention, visuospatial ability, memory, and behavior. Test‐retest reliabilities of latent factors improved to acceptable levels for clinical trials. Applicability and utility of our model was demonstrated by homogeneous effect sizes in the reanalyzed efficacy data. Interpretation These data demonstrate that single observed endpoints are not appropriate to determine efficacy, partly accounting for the poor test‐retest reliability of cognitive outcomes in clinical trials in neurodevelopmental disorders. Recommendations to improve reproducibility are outlined to guide future trial design.

ObjectiveTo investigate the changes in mental health and activities of children with chronic health conditions (CHC) during the pandemic. Additionally, to gather information from parents about their children’s healthcare experience, family stressors and mental health during the COVID-19 pandemic.DesignA prospective longitudinal single site cohort studySettingRoyal Children’s Hospital, Melbourne, AustraliaParticipants151 parents of children aged 1.5-17 years (M = 9.8 years, 58.3% male) with a CHC (colorectal disorder, cleft palate and neurofibromatosis type 1) completed the survey.Main outcome measuresAn adapted version of the COVID-19 Wellbeing and Mental Health Survey for Children and Adolescents (Parent/Caregiver version) (CRISIS) was utilised. The CRISIS tool provides data on child’s activities and mental health and parent mental health prior to, and during, the COVID-19 pandemic. Healthcare experiences families was also examined. Parents completed the Kessler 10.ResultsCompared to pre-COVID lockdown, parents reported their children were experiencing higher rates of loneliness, irritability, worry and anxiety. Parents reported that the restrictions in face-to-face contact with family and friends had been stressful for 80.0% of children. Children’s activities changed considerably during the COVID-19 pandemic with screen time increasing by 40%. Thirty percent of parents reported significant distress of their own. Parents felt telehealth were of poorer quality than face-to-face appointments.ConclusionsChildren with CHC experienced a significant increase in mental health symptoms during lockdown for the COVID-19 pandemic. Our findings highlight the increased need for clinical monitoring for children with CHC during periods of community stress and restrictions.

IMPORTANCE: Social deficits are a common and disabling feature of many pediatric disorders; however, whether behavioral interventions are associated with benefits for children and adolescents with social deficits is poorly understood. OBJECTIVE: To assess whether behavioral interventions in children and adolescents with neurodevelopmental or mental health disorders are associated with improvements in social function and social cognition, and whether patient, intervention, and methodological characteristics moderate the association. DATA SOURCES: For this systematic review and meta-analysis, the PsycINFO, MEDLINE, and PubMed electronic databases were searched in December 2020 for randomized clinical trials published from database inception to December 1, 2020, including terms related to neurodevelopmental or mental health disorders, social behavior, randomized clinical trials, and children and adolescents. Data were analyzed in January 2021. STUDY SELECTION: Randomized clinical trials that enrolled participants aged 4 to 17 years with social deficits and examined the efficacy of a clinician-administered behavioral intervention targeting social functioning or social cognition were included. A total of 9314 records were identified, 78 full texts were assessed for eligibility, and 33 articles were included in the study; 31 of these reported social function outcomes and 12 reported social cognition outcomes. DATA EXTRACTION AND SYNTHESIS: Articles were reviewed using the Cochrane Risk of Bias Assessment for randomized clinical trials. Data were independently extracted and pooled using a weighted random-effects model. MAIN OUTCOMES AND MEASURES: The main outcome was the association of behavioral intervention with social function and social cognition. Hedges g was used to measure the standardized mean difference between intervention and control groups. Standardized effect sizes were calculated for the intervention group vs the comparison group for each trial. RESULTS: A total of 31 trials including 2131 participants (1711 [80%] male; 420 [20%] female; mean [SD] age, 10.8 [2.2] years) with neurodevelopmental or mental health disorders (autism spectrum disorder [ASD] [n = 23], attention-deficit/hyperactivity disorder [n = 4], other conditions associated with social deficits [n = 4]) were analyzed to examine differences in social function between the intervention and control groups. Significantly greater gains in social function were found among participants who received an intervention than among the control groups (Hedges g, 0.61; 95% CI, 0.40-0.83; P

IntroductionChildren with the single-gene disorder neurofibromatosis type 1 (NF1) appear to be at an increased risk for autism spectrum disorder (ASD) and exhibit a unique social-cognitive phenotype compared with children with idiopathic ASD. A complete framework is required to better understand autism in NF1, from neurobiological levels through to behavioural and functional outcomes. The primary aims of this study are to establish the frequency of ASD in children with NF1, examine the social cognitive phenotype, investigate the neuropsychological processes contributing to ASD symptoms and poor social functioning in children with NF1, and to investigate novel structural and functional neurobiological markers of ASD and social dysfunction in NF1. The secondary aim of this study is to compare the neuropsychological and neurobiological features of ASD in children with NF1 to a matched group of patients with idiopathic ASD.Methods and analysisThis is an international, multisite, prospective, cross-sectional cohort study of children with NF1, idiopathic ASD and typically developing (TD) controls. Participants will be 200 children with NF1 (3–15 years of age), 70 TD participants (3–15 years) and 35 children with idiopathic ASD (7–15 years). Idiopathic ASD and NF1 cases will be matched on age, sex and intelligence. All participants will complete cognitive testing and parents will rate their child’s behaviour on standardised questionnaires. Neuroimaging will be completed by a subset of participants aged 7 years and older. Children with NF1 that screen at risk for ASD on the parent-rated Social Responsiveness Scale 2nd Edition will be invited back to complete the Autism Diagnostic Observation Scale 2nd Edition and Autism Diagnostic Interview-Revised to determine whether they fulfil ASD diagnostic criteria.Ethics and disseminationThis study has hospital ethics approval and the results will be disseminated through peer-reviewed publications and international conferences.

Executive dysfunction including impaired goal setting (i.e., planning, organization skills, strategic reasoning) is documented in children born very preterm (VP

Objective To identify distinct language trajectories of children born very preterm and full term from 2 to 13 years of age and examine predictors for the identified trajectories. Study design A cohort of 224 children born very preterm and 77 full term controls recruited at birth were followed up at ages 2, 5, 7, and 13 years. The number of distinct language trajectories was examined using latent growth mixture modeling allowing for linear and quadratic time trends. Potential predictors in the neonatal period (eg, birth group, sex, and medical risk) and at 2 years (ie, social risk and use of allied health services) for the language trajectories were tested using multinomial logistic regression. Results Five distinct language trajectories were identified across childhood: stable normal (32% of study cohort), resilient development showing catch-up (36%), precocious language skills (7%), stable low (17%), and high-risk (5%) development. The very preterm group was 8 times more likely to have a language trajectory that represented poorer language development compared with full term controls (very preterm, 40%; full term, 6%). Greater social risk and use of allied health services were associated with poorer language development. Conclusions Variable language trajectories were observed, with a substantial proportion of children born very preterm exhibiting adverse language development. These findings highlight the need for monitoring language skills in children born very preterm before school entry and across middle childhood.

Objectives:Preterm children demonstrate deficits in executive functions including inhibition, working memory, and cognitive flexibility; however, their goal setting abilities (planning, organization, strategic reasoning) remain unclear. This study compared goal setting abilities between very preterm (VP: Methods:Participants included 177 VP and 61 full-term born control children aged 13 years. Goal setting was assessed using several measures of planning, organization, and strategic reasoning. Parents also completed the Behavior Rating Inventory of Executive Function. Regression models were performed to compare groups, with secondary analyses adjusting for potential confounders (sex and social risk), and excluding children with major neurosensory impairment and/or IQResults:The VP group demonstrated a clear pattern of impairment and inefficiency across goal setting measures, consistent with parental report, compared with their full-term born peers. Within the VP group, moderate/severe brain abnormalities on neonatal MRI predicted adverse goal setting outcomes at 13.Conclusions:Goal setting difficulties are a significant area of concern in VP children during late childhood. These difficulties are associated with neonatal brain abnormalities, and are likely to have functional consequences academically, socially and vocationally. (JINS, 2018,24, 372–381)