Longitudinal cohort study investigating neurodevelopmental and socioemotional outcomes in school-entry aged children after open heart surgery in Australia and New Zealand: the NITRIC follow-up study protocol.

INTRODUCTION: Despite growing awareness of neurodevelopmental impairments in children with congenital heart disease (CHD), there is a lack of large, longitudinal, population-based cohorts. Little is known about the contemporary neurodevelopmental profile and the emergence of specific impairments in children with CHD entering school. The performance of standardised screening tools to predict neurodevelopmental outcomes at school age in this high-risk population remains poorly understood. The NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial randomised 1371 children <2 years of age, investigating the effect of gaseous nitric oxide applied into the cardiopulmonary bypass oxygenator during heart surgery. The NITRIC follow-up study will follow this cohort annually until 5 years of age to assess outcomes related to cognition and socioemotional behaviour at school entry, identify risk factors for adverse outcomes and evaluate the performance of screening tools. METHODS AND ANALYSIS: Approximately 1150 children from the NITRIC trial across five sites in Australia and New Zealand will be eligible. Follow-up assessments will occur in two stages: (1) annual online screening of global neurodevelopment, socioemotional and executive functioning, health-related quality of life and parenting stress at ages 2-5 years; and (2) face-to-face assessment at age 5 years assessing intellectual ability, attention, memory and processing speed; fine motor skills; language and communication; and socioemotional outcomes. Cognitive and socioemotional outcomes and trajectories of neurodevelopment will be described and demographic, clinical, genetic and environmental predictors of these outcomes will be explored. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Children's Health Queensland (HREC/20/QCHQ/70626) and New Zealand Health and Disability (21/NTA/83) Research Ethics Committees. The findings will inform the development of clinical decision tools and improve preventative and intervention strategies in children with CHD. Dissemination of the outcomes of the study is expected via publications in peer-reviewed journals, presentation at conferences, via social media, podcast presentations and medical education resources, and through CHD family partners. TRIAL REGISTRATION NUMBER: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry as 'Gene Expression to Predict Long-Term Neurodevelopmental Outcome in Infants from the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) Study - A Multicentre Prospective Trial'. TRIAL REGISTRATION: ACTRN12621000904875.

Outcomes in mild hyperphenylalaninemia: a comparison with PKU and healthy controls across cognition, behaviour, and quality of life.

AIMS: Considering the cognitive, behavioural and quality of life (QoL) consequences of high phenylalanine levels in early treated phenylketonuria (PKU), this study examined whether monitoring and active management of individuals with the mild form of the condition hyperphenylalaninemia (HPA) would be advisable. METHOD: Six individuals (aged 6 to 15) with untreated HPA were compared with six age and gender matches with PKU, and six healthy controls on the Wechsler Intelligence Scale for Children, 5th edition; Wechsler Individual Achievement Test, 2nd edition; Trail-Making test; Contingency Naming Test; and Oral Fluency test. Self- and parent-report rating scales administered included the Conners Comprehensive Behavior Rating Scales; Behavior Rating Inventory of Executive Function, 2nd edition; the Pediatric Quality of Life Inventory, and the Phenylketonuria Quality of Life (PKU group only) questionnaires. RESULTS: Early treated PKU participants demonstrated normal intelligence, pointing to the efficacy of dietary management. Quality of life and behavioural difficulties were observed including more severe externalising problems. HPA participants showed normal ability, including executive ability. Power was limited by the small sample. CONCLUSION: This was the first study of the New Zealand population with HPA. While there was insufficient evidence to warrant treatment, there was also insufficient evidence to safely exclude the presence of cognitive impairment.

Systematic Review of Screening Instruments for Psychosocial Problems in Children and Adolescents With Long-Term Physical Conditions.

Children and adolescents with long-term physical conditions (LTPCs) are at greater risk of developing psychosocial problems. Screening for such problems may be undertaken using validated psychometric instruments to facilitate early intervention. A systematic review was undertaken to identify clinically utilized and psychometrically validated instruments for identifying depression, anxiety, behavior problems, substance use problems, family problems, and multiple problems in children and adolescents with LTPCs. Comprehensive searches of articles published in English between 1994 and 2014 were completed via Medline, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL databases, and by examining reference lists of identified articles and previous related reviews. Forty-four potential screening instruments were identified, described, and evaluated against predetermined clinical and psychometric criteria. Despite limitations in the evidence regarding their clinical and psychometric validity in this population, a handful of instruments, available at varying cost, in multiple languages and formats, were identified to support targeted, but not universal, screening for psychosocial problems in children and adolescents with LTPCs.