Mental health problems in children with intellectual disability

Intellectual disability ranks in the top ten causes of disease burden globally and is the top cause in children younger than 5 years. 2-3% of children have an intellectual disability, and about 15% of children present with differences consistent with an intellectual disability (ie, global developmental delay and borderline intellectual functioning). In this Review, we discuss the prevalence of mental health problems, interventions to address these, and issues of access to treatment and services. Where possible, we take a global perspective, given most children with intellectual disability live in low-income and middle-income countries. Approximately 40% of children with intellectual disability present with a diagnosable mental disorder, a rate that is at least double that in children without intellectual disability. Most risk factors for poor mental health and barriers to accessing support are not unique to people with intellectual disability. With proportionate universalism as the guiding principle for reducing poor mental health at scale, we discuss four directions for addressing the mental health inequity in intellectual disability

Association of cognitive and adaptive skills with internalizing and externalizing problems in autistic children and adolescents

The presence of an intellectual disability (ID) alongside autism is considered to increase the risk for mental health and behavior problems in children and adolescents. Existing evidence is restricted by looking at ID as a categorical classification. The study aimed to examine the association of cognitive and adaptive behavior skills with internalizing and externalizing problems in a large sample of autistic children and adolescents, across a wide range of cognitive skills. Participants were 2759 children and adolescents aged between 4 and 18 years recruited as part of the Simons Simplex Collection (SSC), of whom 709 (approximately 25%) had ID. Multiple regression models examined associations of internalizing and externalizing problems with cognitive and adaptive skills (communication, daily living, and socialization skills). Cognitive skills were not associated with externalizing problems but were associated with more internalizing problems in autistic children without ID (Cog β: 0.126). All adaptive skill domains were inversely associated with externalizing (Communication β: −0.145; Daily-Living β: −0.132; Socialization β: −0.289) and internalizing problems (Communication β: −0.074; Daily-Living β: −0.064; Socialization β: −0.213) in those without ID. Daily living (β: −0.158) and socialization skills (β: −0.104) were inversely correlated with externalizing problems in autistic children with ID, while only socialization problems (β: −0.099) were associated with internalizing problems in this group. Socialization skills were systematically associated with internalizing and externalizing problems across all levels of cognitive functioning. Supporting social skills development may benefit all aspects of child mental health, while recognizing that children with higher cognitive skills are more vulnerable to internalizing problems might assist with earlier identification of these problems

Prevalence and Predictors of Vitamin D Insufficiency in Children: A Great Britain Population Based Study

Objectives To evaluate the prevalence and predictors of vitamin D insufficiency (VDI) in children In Great Britain. Design A nationally representative cross-sectional study survey of children (1102) aged 4–18 years (999 white, 570 male) living in private households (January 1997–1998). Interventions provided information about dietary habits, physical activity, socio-demographics, and blood sample. Outcome measures were vitamin D insufficiency (<50 nmol/L). Results Vitamin D levels (mean = 62.1 nmol/L, 95%CI 60.4–63.7) were insufficient in 35%, and decreased with age in both sexes (p<0.001). Young People living between 53–59 degrees latitude had lower levels (compared with 50–53 degrees, p = 0.045). Dietary intake and gender had no effect on vitamin D status. A logistic regression model showed increased risk of VDI in the following: adolescents (14–18 years old), odds ratio (OR) = 3.6 (95%CI 1.8–7.2) compared with younger children (4–8 years); non white children (OR = 37 [95%CI 15–90]); blood levels taken December-May (OR = 6.5 [95%CI 4.3–10.1]); on income support (OR = 2.2 [95%CI 1.3–3.9]); not taking vitamin D supplementation (OR = 3.7 [95%CI 1.4–9.8]); being overweight (OR 1.6 [95%CI 1.0–2.5]); <1/2 hour outdoor exercise/day/week (OR = 1.5 [95%CI 1.0–2.3]); watched >2.5 hours of TV/day/week (OR = 1.6[95%CI 1.0–2.4]). Conclusion We confirm a previously under-recognised risk of VDI in adolescents. The marked higher risk for VDI in non-white children suggests they should be targeted in any preventative strategies. The association of higher risk of VDI among children who exercised less outdoors, watched more TV and were overweight highlights potentially modifiable risk factors. Clearer guidelines and an increased awareness especially in adolescents are needed, as there are no recommendations for vitamin D supplementation in older children

Intravenous immunoglobulin treatment in childhood encephalitis (IgNiTE): a randomised controlled trial

Objective: To investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness. // Design: Phase 3b multicentre, double-blind, randomised placebo-controlled trial. // Setting: Twenty-one hospitals in the UK. // Participants: Children aged 6 months to 16 years with a diagnosis of acute or subacute encephalitis, with a planned sample size of 308. // Intervention: Two doses (1 g/kg/dose) of either IVIG or matching placebo given 24–36 hours apart, in addition to standard treatment. // Main outcome measure: The primary outcome was a ‘good recovery’ at 12 months after randomisation, defined as a score of≤2 on the Paediatric Glasgow Outcome Score Extended. // Secondary outcome measures: The secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and IVIG safety data. // Results: 18 participants were recruited from 12 hospitals and randomised to receive either IVIG (n=10) or placebo (n=8) between 23 December 2015 and 26 September 2017. The study was terminated early following withdrawal of funding due to slower than anticipated recruitment, and therefore did not reach the predetermined sample size required to achieve the primary study objective; thus, the results are descriptive. At 12 months after randomisation, 9 of the 18 participants (IVIG n=5/10 (50%), placebo n=4/8 (50%)) made a good recovery and 5 participants (IVIG n=3/10 (30%), placebo n=2/8 (25%)) made a poor recovery. Three participants (IVIG n=1/10 (10%), placebo n=2/8 (25%)) had a new diagnosis of epilepsy during the study period. Two participants were found to have specific autoantibodies associated with autoimmune encephalitis. No serious adverse events were reported in participants receiving IVIG. // Conclusions: The IgNiTE (ImmunoglobuliN in the Treatment of Encephalitis) study findings support existing evidence of poor neurological outcomes in children with encephalitis. However, the study was halted prematurely and was therefore underpowered to evaluate the effect of early IVIG treatment compared with placebo in childhood encephalitis. // Trial registration number: Clinical Trials.gov NCT02308982; ICRCTN registry ISRCTN15791925

Vitamin D and antimicrobial peptide levels in patients with atopic dermatitis and atopic dermatitis complicated by eczema herpeticum: A pilot study.

In this study, Vitamin D supplementation results in improved clinical severity of atopic dermatitis and increased skin surface LL-37 levels, analyzed by a novel, non-invasive method. Vitamin D supplementation could be a therapeutic option in AD

Clinical and cost-effectiveness of an adapted intervention for preschoolers with moderate to severe intellectual disabilities displaying behaviours that challenge: the EPICC-ID RCT

BACKGROUND: Stepping Stones Triple P is an adapted intervention for parents of young children with developmental disabilities who display behaviours that challenge, aiming at teaching positive parenting techniques and promoting a positive parent-child relationship. OBJECTIVE: To evaluate the clinical and cost-effectiveness of level 4 Stepping Stones Triple P in reducing behaviours that challenge in children with moderate to severe intellectual disabilities. DESIGN, SETTING, PARTICIPANTS: A parallel two-arm pragmatic multisite single-blind randomised controlled trial recruited a total of 261 dyads (parent and child). The children were aged 30-59 months and had moderate to severe intellectual disabilities. Participants were randomised, using a 3 : 2 allocation ratio, into the intervention arm (Stepping Stones Triple P; n = 155) or treatment as usual arm (n = 106). Participants were recruited from four study sites in Blackpool, North and South London and Newcastle. INTERVENTION: Level 4 Stepping Stones Triple P consists of six group sessions and three individual phone or face-to-face contacts over 9 weeks. These were changed to remote sessions after 16 March 2020 due to the coronavirus disease 2019 pandemic. MAIN OUTCOME MEASURE: The primary outcome measure was the parent-reported Child Behaviour Checklist, which assesses the severity of behaviours that challenge. RESULTS: We found a small non-significant difference in the mean Child Behaviour Checklist scores (-4.23, 95% CI -9.98 to 1.52, p = 0.146) in the intervention arm compared to treatment as usual at 12 months. Per protocol and complier average causal effect sensitivity analyses, which took into consideration the number of sessions attended, showed the Child Behaviour Checklist mean score difference at 12 months was lower in the intervention arm by -10.77 (95% CI -19.12 to -2.42, p = 0.014) and -11.53 (95% CI -26.97 to 3.91, p = 0.143), respectively. The Child Behaviour Checklist mean score difference between participants who were recruited before and after the coronavirus disease 2019 pandemic was estimated as -7.12 (95% CI -13.44 to -0.81) and 7.61 (95% CI -5.43 to 20.64), respectively (p = 0.046), suggesting that any effect pre-pandemic may have reversed during the pandemic. There were no differences in all secondary measures. Stepping Stones Triple P is probably value for money to deliver (-£1057.88; 95% CI -£3218.6 to -£46.67), but decisions to roll this out as an alternative to existing parenting interventions or treatment as usual may be dependent on policymaker willingness to invest in early interventions to reduce behaviours that challenge. Parents reported the intervention boosted their confidence and skills, and the group format enabled them to learn from others and benefit from peer support. There were 20 serious adverse events reported during the study, but none were associated with the intervention. LIMITATIONS: There were low attendance rates in the Stepping Stones Triple P arm, as well as the coronavirus disease 2019-related challenges with recruitment and delivery of the intervention. CONCLUSIONS: Level 4 Stepping Stones Triple P did not reduce early onset behaviours that challenge in very young children with moderate to severe intellectual disabilities. However, there was an effect on child behaviours for those who received a sufficient dose of the intervention. There is a high probability of Stepping Stones Triple P being at least cost neutral and therefore worth considering as an early therapeutic option given the long-term consequences of behaviours that challenge on people and their social networks. FUTURE WORK: Further research should investigate the implementation of parenting groups for behaviours that challenge in this population, as well as the optimal mode of delivery to maximise engagement and subsequent outcomes. STUDY REGISTRATION: This study is registered as NCT03086876 (https://www.clinicaltrials.gov/ct2/show/NCT03086876?term=Hassiotis±Angela&draw=1&rank=1). FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: HTA 15/162/02) and is published in full in Health Technology Assessment; Vol. 28, No. 6. See the NIHR Funding and Awards website for further award information

Intravenous immunoglobulin treatment for encephalitis in children aged 6 months to 16 years: the IgNiTE RCT

Background: There are data suggesting that intravenous immunoglobulin treatment has some benefit for certain forms of encephalitis but robust evidence from large randomised controlled trials in children with all-cause encephalitis is lacking. Objective: To evaluate whether intravenous immunoglobulin treatment improves neurological outcomes in childhood encephalitis when given early in the illness. Design: Phase 3b, investigator-initiated, randomised, double-blind, placebo-controlled trial of intravenous immunoglobulin for the treatment of encephalitis in children. Setting: Twenty-one NHS Hospitals in the UK. Participants: Children aged 6 months to 16 years with a diagnosis of acute or sub-acute encephalitis. Intervention: Two doses (1 g/kg/dose) of either intravenous immunoglobulin or matching placebo, given 24–36 hours apart, in addition to standard treatment. Main outcome measure: Participants were followed up for 12 months (+/– 4 weeks) after randomisation. The primary outcome measure was a ‘good recovery’ defined as a score of ≤ 2 on the Paediatric Glasgow Outcome Score Extended at 12 months after randomisation. Secondary outcomes: The secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and intravenous immunoglobulin safety data. Results: We planned to recruit 308 children over a 42-month period. After enrolment of 18 participants (8 male; 44%) over 21 months (from December 2015 to September 2017), funding was withdrawn due to slow recruitment and the study was terminated. Ten participants were randomised to the intravenous immunoglobulin group, and eight to the placebo group, and all 18 participants were included in the analysis. At 12 months after randomisation, 9 participants [50%; intravenous immunoglobulin n = 5 (50%), placebo n = 4 (50%)] made good recovery and 5 participants [28%; intravenous immunoglobulin n = 3 (30%), placebo n = 2 (25%)] made a poor recovery. Three participants in the placebo group (43%) experienced a total of 10 serious adverse events compared with none in the intravenous immunoglobulin group but none of the adverse events were judged to be related to the study treatment. No deaths occurred during the study period. Conclusion: ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE) was halted prematurely due to slow recruitment. Given the small sample size, the study was underpowered to evaluate the effect of intravenous immunoglobulin when compared with placebo in childhood encephalitis. The study findings, albeit from a small sample size, support existing evidence that encephalitis results in poor neurological outcomes for many children. Lessons learned from the ImmunoglobuliN in the Treatment of Encephalitis trial would be valuable for the success of future trials set up to address the efficacy of early treatment with intravenous immunoglobulin in all-cause encephalitis in children. Study limitations and future work: The study was underpowered to evaluate the efficacy of intravenous immunoglobulin in the treatment of childhood encephalitis due to the small sample size achieved. Future trials should seek to address this important question. Trial registration: This trial is registered as Clinical Trials.gov (NCT02308982) and ISRCTN15791925. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/212/15) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 6. See the NIHR Funding and Awards website for further award information

Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures

Objective: We aimed to describe the extent of neurodevelopmental impairments andidentify the genetic etiologies in a large cohort of patients with epilepsy with myoclonicatonic seizures (MAE).Methods: We deeply phenotyped MAE patients for epilepsy features, intellectualdisability, autism spectrum disorder, and attention-deficit/hyperactivity disorderusing standardized neuropsychological instruments. We performed exome analysis(whole exome sequencing) filtered on epilepsy and neuropsychiatric gene sets toidentify genetic etiologies.Results: We analyzed 101 patients with MAE (70% male). The median age of seizureonset was 34 months (range = 6-72 months). The main seizure types were myoclonicatonic or atonic in 100%, generalized tonic-clonic in 72%, myoclonic in 69%, absencein 60%, and tonic seizures in 19% of patients. We observed intellectual disability in62% of patients, with extremely low adaptive behavioral scores in 69%. In addition,24% exhibited symptoms of autism and 37% exhibited attention-deficit/hyperactivitysymptoms. We discovered pathogenic variants in 12 (14%) of 85 patients, includingfive previously published patients. These were pathogenic genetic variants inSYNGAP1 (n = 3), KIAA2022 (n = 2), and SLC6A1 (n = 2), as well as KCNA2,SCN2A, STX1B, KCNB1, and MECP2 (n = 1 each). We also identified three newcandidate genes, ASH1L, CHD4, and SMARCA2 in one patient each.Significance: MAE is associated with significant neurodevelopmental impairment.MAE is genetically heterogeneous, and we identified a pathogenic genetic etiologyin 14% of this cohort by exome analysis. These findings suggest that MAE is a manifestationof several etiologies rather than a discrete syndromic entity

Mapping the pathway and support offered to children with an intellectual disability referred to specialist mental health services in the UK.

This survey of 66 specialist mental health services aimed to provide an up-to-date description of pathways of care and interventions available to children with an intellectual disability referred for behaviours that challenge or with suspected mental health problems. Overall, 24% of services made contact with a family at referral stage, whereas 29% contacted families at least once during the waiting list phase. Only two in ten services offered any therapeutic input during the referral or waiting list stages. During the active caseload phase, services offered mostly psychoeducation (52-59%), followed by applied behaviour analytic approaches for behaviours that challenge (52%) and cognitive-behavioural therapy (41%). Thirty-six per cent of services had not offered any packaged or named intervention in the past 12 months. With increasing waiting times for specialist mental health support, services need to consider increasing the amount of contact and therapeutic input on offer throughout all stages of a child's journey with the service