Sleep in Down Syndrome

Sleep disorders are common, often overlooked problem in Down syndrome, particularly during childhood. Comorbidities such as congenital heart disease often present early and management of these needs to take priority. However, this can result in the lack of early development of good sleep habits and may also lead to the perception that sleep issues are an expected problem in children with Down syndrome, which do not require intervention. Studies have shown that sleep problems continue to be under-reported by parents of children with Down syndrome, even though conditions such as obstructive sleep apnoea are up to six times more common in this population. Therefore an understanding of the nature of sleep problems in Down syndrome is important for anyone working with this group. In this chapter we provide an overview of this topic, highlighting the key sleep issues encountered by children with Down syndrome, as well as providing a general approach to evaluation and management

Exploring the association between perceived excessive daytime sleepiness in children and academic outcomes

Excessive daytime sleepiness (EDS) in children has been associated with a number of problems. In contrast to adults who experience EDS and who may fall asleep or doze when in a monotonous or boring situation, children with EDS may present as hyperactive or poorly behaved. This community-based study aims to identify the prevalence of EDS in children from three perspectives: parent report, self-report, and teacher report. The study also explores the association between EDS and academic outcomes in children. The participants were 365 students (161 males) aged 4-12 years, their parents, and their teachers at a regional school. Academic outcomes were based on each student's school grades at the conclusion of the semester in which the community-based survey was administered. Using a cutoff score of 15 or greater on the PDSS, 113 (31%) students were identified by at least one respondent as displaying or experiencing EDS. EDS as observed by teachers using the PDSS was found to be associated with the student's academic outcomes, higher sleepiness scores being associated with poorer academic outcomes. Our findings suggest that the prevalence of EDS in a community setting may be higher than previously identified

Brief Report: An evaluation of an Australian autism-specific, early intervention programme

There is a relative paucity of evidence examining the effectiveness of early intervention for young children with Autism Spectrum Disorder, in particular those delivered through educationally-based programmes. This study aimed to evaluate the real world effectiveness of a community-based autism-specific early learning and intervention programme in Australia. Children enrolled between February 2010 and May 2013 who had a diagnosis of an Autism Spectrum Disorder was eligible to participate in the study. Fifty-nine children with a mean age of 3.98 years participated. Cognitive ability, language, autistic symptoms, and motor skills were assessed at baseline and follow up (12 months or at programme exit) using standardised measures. Pre- and post-measures were compared using paired sample t-tests. Significant improvements were found in receptive and expressive language, autism symptoms, and overall adaptive behaviour. No significant change was found in motor skills. Children with Autism Spectrum Disorder attending the community-based programme had significant gains particularly in domains of cognition and language. Study limitations are discussed

Melatonin in Youth: N-of-1 trials in a stimulant-treated ADHD Population (MYNAP): study protocol for a randomized controlled trial

Attention-deficit/hyperactivity disorder (ADHD) is a common neurological disorder affecting 5\ua0% of children worldwide. A prevalent problem for children with ADHD is initial insomnia. The gold standard treatment to manage ADHD symptoms is stimulant medications, which may exacerbate the severity of existing initial insomnia. Currently, no gold standard treatment option exists for initial insomnia for these children. Melatonin, a hormone and a popular natural health product, is commonly provided to children by parents and recommended by healthcare providers, but high quality pediatric evidence is lacking.This trial is a multicenter randomized triple-blind, placebo-controlled, parallel-group, randomized, controlled trial (RCT), in which each participant is offered an N-of-1 trial. An N-of-1 trial is a multiple-crossover, randomized, controlled trial conducted in a single individual. For the N-of-1 trial, each participant will undergo three pairs of treatment/placebo periods; each period is 1\ua0week in length. Half the participants will have melatonin in the first period, the other half will start with placebo, and this will make up the parallel-group RCT. The primary outcome will be mean difference in sleep onset latency as measured by sleep diaries. A comparison of treatment effects yielded by the RCT data versus the aggregated N-of-1 trial data will also be assessed.This trial will provide rigorous evidence for the effectiveness of melatonin in children with ADHD on stimulants who experience initial insomnia. Further, this study will provide the first prospectively planned head-to-head comparison of RCT data with pooled data from a series of N-of-1 trials. Aggregated N-of-1 trials may be a powerful tool to produce high quality clinical trial evidence.ClinicalTrials.gov, NCT02333149 . Registered on 16 December 2014. Australian New Zealand Clinical Trials Registry, ACTRN12614000542695 . Registered on 21 May 2014

Rationale for and design of the "POSTA" study: Evaluation of neurocognitive outcomes after immediate adenotonsillectomy compared to watchful waiting in preschool children

Background: IQ deficits are linked to even mild obstructive sleep apnoea (OSA) in children. Although OSA is commonly first diagnosed in the pre-school age group, a randomised trial is still needed to assess IQ outcomes after adenotonsillectomy in the pre-school age-group. This randomised control trial (RCT) will primarily determine whether adenotonsillectomy improves IQ compared to no adenotonsillectomy after 12 months, in preschool (3–5 year-old) children with mild to moderate OSA. Methods: This protocol is for an ongoing multi-centred RCT with a recruitment target of 210 subjects (105 in each arm). Children age 3–5 years with symptoms of OSA, are recruited through doctor referral, at the point of referral to the Ear Nose and Throat (ENT) services. Screening is initially with a questionnaire (Paediatric Sleep Questionnaire, PSQ) for symptoms of obstructive sleep apnoea (OSA). Where questionnaires are positive (suggestive of OSA) and ENT surgeons recommend them for adenotonsillectomy, they are invited to participate in POSTA. Baseline testing includes neurocognitive testing (IQ and psychometric evaluation with the neuropsychologist blinded to randomisation) and overnight polysomnography (PSG). Where the Obstructive Apnoea-Hypopnea Index (OAHI) from the PSG is <10/h per hour, consent for randomisation is sought; children with severe OSA (OAHI ≥ 10/h) are sent for immediate treatment and excluded from the study. After consent is obtained, participants are randomised to early surgery (within 2 months) or to surgery after a usual wait time of 12 months. Follow-up studies include repeat neurocognitive testing and PSG at 12 (with the waiting list group studied before their surgery) and 24 months after randomisation. Analysis will be by intention to treat. The primary outcome is IQ at 12 months’ follow-up. Discussion: If IQ deficits associated with OSA are reversible 12 months after adenotonsillectomy compared to controls, future clinical practice advise would be to undertake early surgery in young children with OSA. The study could provide data on whether a window of opportunity exists for reversing IQ deficits linked to OSA in the pre-school age-group. Trial registration: Australian and New Zealand Clinical Trials Registration Number ACTRN12611000021976.Karen A. Waters, Jasneek Chawla, Margaret-Anne Harris, Carolyn Dakin, Helen Heussler, Robert Black, Alan Cheng, Hannah Burns, John D. Kennedy and Kurt Lushingto

Study protocol for the Australian autism biobank: an international resource to advance autism discovery research

BACKGROUND: The phenotypic and genetic heterogeneity of autism spectrum disorder (ASD) presents considerable challenges in understanding etiological pathways, selecting effective therapies, providing genetic counselling, and predicting clinical outcomes. With advances in genetic and biological research alongside rapid-pace technological innovations, there is an increasing imperative to access large, representative, and diverse cohorts to advance knowledge of ASD. To date, there has not been any single collective effort towards a similar resource in Australia, which has its own unique ethnic and cultural diversity. The Australian Autism Biobank was initiated by the Cooperative Research Centre for Living with Autism (Autism CRC) to establish a large-scale repository of biological samples and detailed clinical information about children diagnosed with ASD to facilitate future discovery research. METHODS: The primary group of participants were children with a confirmed diagnosis of ASD, aged between 2 and 17 years, recruited through four sites in Australia. No exclusion criteria regarding language level, cognitive ability, or comorbid conditions were applied to ensure a representative cohort was recruited. Both biological parents and siblings were invited to participate, along with children without a diagnosis of ASD, and children who had been queried for an ASD diagnosis but did not meet diagnostic criteria. All children completed cognitive assessments, with probands and parents completing additional assessments measuring ASD symptomatology. Parents completed questionnaires about their child's medical history and early development. Physical measurements and biological samples (blood, stool, urine, and hair) were collected from children, and physical measurements and blood samples were collected from parents. Samples were sent to a central processing site and placed into long-term storage. DISCUSSION: The establishment of this biobank is a valuable international resource incorporating detailed clinical and biological information that will help accelerate the pace of ASD discovery research. Recruitment into this study has also supported the feasibility of large-scale biological sample collection in children diagnosed with ASD with comprehensive phenotyping across a wide range of ages, intellectual abilities, and levels of adaptive functioning. This biological and clinical resource will be open to data access requests from national and international researchers to support future discovery research that will benefit the autistic community

A national harmonised data collection network for neurodevelopmental disorders: A transdiagnostic assessment protocol for neurodevelopment, mental health, functioning and well-being

BACKGROUND: Children with neurodevelopmental disorders share common phenotypes, support needs and comorbidities. Such overlap suggests the value of transdiagnostic assessment pathways that contribute to knowledge about research and clinical needs of these children and their families. Despite this, large transdiagnostic data collection networks for neurodevelopmental disorders are not well developed. This paper describes the development of a nationally supported transdiagnostic clinical and research assessment protocol across Australia. The vision is to establish a harmonised network for data collection and collaboration that promotes transdiagnostic clinical practice and research. METHODS: Clinicians, researchers and community groups across Australia were consulted using surveys and national summits to identify assessment instruments and unmet needs. A national research committee was formed and, using a consensus approach, selected assessment instruments according to pre-determined criteria to form a harmonised transdiagnostic assessment protocol. RESULTS: Identified assessment instruments were clustered into domains of transdiagnostic assessment needs, which included child functioning/quality of life, child mental health, caregiver mental health, and family background information. From this, the research committee identified a core set of nine measures and an extended set of 14 measures that capture these domains with potential for further modifications as recommended by clinicians, researchers and community members. CONCLUSION: The protocol proposed here was established through a strong partnership between clinicians, researchers and the community. It will enable (i) consensus driven transdiagnostic clinical assessments for children with neurodevelopmental disorders, and (ii) research studies that will inform large transdiagnostic datasets across neurodevelopmental disorders and that can be used to inform research and policy beyond narrow diagnostic groups. The long-term vision is to use this framework to facilitate collaboration across clinics to enable large-scale data collection and research. Ultimately, the transdiagnostic assessment data can be used to inform practice and improve the lives of children with neurodevelopmental disorders and their families

A case-control genome-wide association study of ADHD discovers a novel association with the tenascin R (TNR) gene

This work has been supported by Project Grant funding from the National Health and Medical Research Council (NHMRC) of Australia to Z.H. (1006573, 1002458 and 1065677) and M.A.B. (569636, 1065677, 1045354, 1002458 and 1006573).It is well-established that there is a strong genetic contribution to the aetiology of attention deficit hyperactivity disorder (ADHD). Here, we employed a hypothesis-free genome-wide association study (GWAS) design in a sample of 480 clinical childhood ADHD cases and 1208 controls to search for novel genetic risk loci for ADHD. DNA was genotyped using Illumina’s Human Infinium PsychArray-24v1.2., and the data were subsequently imputed to the 1000 Genomes reference panel. Rigorous quality control and pruning of genotypes at both individual subject and single nucleotide polymorphism (SNP) levels was performed. Polygenic risk score (PGRS) analysis revealed that ADHD case–control status was explained by genetic risk for ADHD, but no other major psychiatric disorders. Logistic regression analysis was performed genome-wide to test the association between SNPs and ADHD case–control status. We observed a genome-wide significant association (p = 3.15E−08) between ADHD and rs6686722, mapped to the Tenascin R (TNR) gene. Members of this gene family are extracellular matrix glycoproteins that play a role in neural cell adhesion and neurite outgrowth. Suggestive evidence of associations with ADHD was observed for an additional 111 SNPs (⩽9.91E−05). Although intriguing, the association between DNA variation in the TNR gene and ADHD should be viewed as preliminary given the small sample size of this discovery dataset.Publisher PDFPeer reviewe