Neuropsychiatric risk in children with intellectual disability of genetic origin: IMAGINE, a UK national cohort study

Background Children with intellectual disability frequently have multiple co-morbid neuropsychiatric conditions and poor physical health. Genomic testing is increasingly recommended as a first-line investigation for these children. We aim to determine the effect of genomics, inheritance, and socioeconomic deprivation on neuropsychiatric risk in children with intellectual disability of genetic origin as compared with the general population. Methods IMAGINE is a prospective cohort study using online mental health and medical assessments in a cohort of 3407 UK participants with intellectual disability and pathogenic genomic variants as identified by the UK's National Health Service (NHS). Our study is on a subset of these participants, including all children aged 4–19 years. We collected diagnostic genomic reports from NHS records and asked primary caregivers to provide an assessment of their child using the Development and Well-Being Assessment (DAWBA), the Strengths and Difficulties Questionnaire (SDQ), the Adaptive Behaviour Assessment System 3 (ABAS-3), and a medical history questionnaire. Each child was assigned a rank based on their postcode using the index of multiple deprivation (IMD). We compared the IMAGINE cohort with the 2017 National Survey of Children's Mental Health in England. The main outcomes of interest were mental health and neurodevelopment according to the DAWBA and SDQ. Findings We recruited 2770 children from the IMAGINE study between Oct 1, 2014 and June 30, 2019, of whom 2397 (86·5%) had a basic assessment of their mental health completed by their families and 1277 (46·1%) completed a medical history questionnaire. The mean age of participants was 9·2 years (SD 3·9); 1339 (55·9%) were boys and 1058 (44·1%) were girls. 355 (27·8%) of 1277 reported a seizure disorder and 814 (63·7%) reported movement or co-ordination problems. 1771 (73·9%) of 2397 participants had a pathogenic copy number variant (CNV) and 626 (26·1%) had a pathogenic single nucleotide variant (SNV). Participants were representative of the socioeconomic spectrum of the UK general population. The relative risk (RR) of co-occurring neuropsychiatric diagnoses, compared with the English national population, was high: autism spectrum disorder RR 29·2 (95% CI 23·9–36·5), ADHD RR 13·5 (95% CI 11·1–16·3). In children with a CNV, those with a familial variant tended to live in more socioeconomically deprived areas than those with a de novo variant. Both inheritance and socioeconomic deprivation contributed to neuropsychiatric risk in those with a CNV. Interpretation Children with genomic variants and intellectual disability are at an increased risk of neuropsychiatric difficulties. CNV variant inheritance and socioeconomic deprivation also contribute to the risk. Early genomic investigations of children with intellectual disability could facilitate the identification of the most vulnerable children. Additionally, harnessing parental expertise using online DAWBA assessments could rapidly identify children with exceptional needs to child mental health services

Multicountry review : developmental surveillance, assessment and care by outpatient paediatricians

BACKGROUND: Care of young children with neurodevelopmental disorders (NDD) is a major component of paediatric outpatient practice. However, cross-country practice reviews to date have been limited, and available data demonstrate missed opportunities for early identification, particularly in vulnerable population subgroups. METHODS: Multicountry review of national paediatric body guidance related to developmental surveillance, early identification and early childhood intervention together with review of outpatient paediatrician practices for developmental assessment of children aged 0-5 years with/at risk of NDDs. Review included five countries with comparable nationalised universal child healthcare systems (ie, Australia, Canada, New Zealand, Sweden and the UK). Data were collected using a combination of published and grey literature review, supplemented by additional local sources with descriptive review of relevant data points. RESULTS: Countries had broadly similar systems for early identification of young children with NDDs alongside universal child health surveillance. However, variation existed in national paediatric guidance, paediatric developmental training and practice, including variable roles of paediatricians in developmental surveillance at primary care level. Data on coverage of developmental surveillance, content and quality of paediatric development assessment practices were notably lacking. CONCLUSION: Paediatricians play an important role in ensuring equitable access to early identification and intervention for young children with/at risk of NDDs. However, strengthening paediatric outpatient care of children with NDD requires clearer guidance across contexts; training that is responsive to shifting roles within interdisciplinary models of developmental assessment and improved data to enhance equity and quality of developmental assessment for children with/at risk of NDDs