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ObjectivesThere is limited information about the stability and predictability of Bayley Scales of Infant and Toddler Development (BSID) assessing child development in low- and middle-income settings. The objective of the present study was to analyse stability and predictive validity of BSID using an existing birth cohort.DesignProspective birth cohort follow-up study.Setting and participantsA community-based birth cohort of 251 newborns was recruited and followed-up in urban Vellore, South India, until 9 years of age. Using BSID-III, child development was measured at 6, 15, 24 and 36 months. Cognition was assessed using the Wechsler Preschool Primary Scales of Intelligence at 5 years, and the Malin’s Intelligence Scale for Indian Children scale at 7 and 9 years of age. The stability of BSID measurements across time points was expressed by intraclass correlation (ICC) and concordance correlation coefficients. Linear regression was used to describe the predictability of BSID-III of cognition at 5, 7 and 9 years.ResultsThe ICC for domain-wise BSID scores between time points of measurement suggested a weak correlation. The BSID scores at 36 months correlated best with Full-Scale Intelligence Quotient (FSIQ) at 5 years (r: 0.40–0.49), 7 years (r: 0.35–0.48) and 9 years (r: 0.36–0.38). BSID scores at 36 months predicted FSIQ better at 5, 7 and 9 years with R2 ranging from 23.3% to 28.6%, when compared with 24 months BSID scores (R2 - 16.0% to 25.9%).ConclusionPoor stability and predictability of BSID warrant caution in the predictive projection of early childhood assessments. Better predictability of future cognition of 36 months’ BSID scores highlights its advantage over the 24 months’ assessment.

Investigate predictors of adverse outcome in children with and without attention-deficit/hyperactivity disorder (ADHD) combined with developmental coordination disorder (DCD) at 6 years of age. Prospective population-based cohort study. Western Sweden. From a screening-based population cohort of 589 individuals, 62 (11 female) diagnosed with ADHD+DCD at mean age 6.6 years, and a comparison group of 51 population-matched (10 female) children were followed prospectively. Drawn from a clinical reassessment at age 9 years of 110 of the 113 individuals, neuropsychiatric symptoms, continuous performance test results and measures of motor function were used as predictors of outcome in linear regression models. Participants were followed in national registers up to 30-31 years of age for outcomes in adulthood. Predictors were regressed onto an adverse outcome score (range 0-7) comprising seven binary endpoints, and when applicable onto each continuous outcome separately (low educational attainment, low occupation level, psychiatric disorder, psychotropic medication prescription, sick pension, high dependence on social benefits and criminal conviction). Of the 110 individuals, 3 had died. In univariable regression onto the adverse outcome score, the strongest predictors at age 9 years were symptoms of conduct disorder, oppositional defiant disorder, ADHD and motor dysfunction, with an R around 25%, followed by autistic traits (R =15%) and depressive symptoms (R =8%). Combining these six strongest predictors in a multivariable model yielded an adjusted R =38%. Subgroup analyses were similar, except for a strong association of autistic traits with the adverse outcome score in females (n=20, R =50%). Several neurodevelopmental symptoms, including ADHD severity at age 9 years, accounted for a considerable amount of the variance in terms of adulthood adverse outcome. Broad neurodevelopmental profiling irrespective of diagnostic thresholds should inform research and clinical practice. The study highlights the importance of considering associated comorbidities and problems in ADHD.

ObjectivesThis study aimed to examine the association between infertility treatment and neurodevelopment in children at 2 and 3.5 years of age.DesignProspective cohort study.Setting and participantsThe study population consisted of mother–child pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Miyagi and Iwate Prefectures, Japan. Pregnant women were recruited in obstetric clinics or hospitals and their children were followed up by the questionnaire.Outcome measuresThe children’s neurodevelopmental outcomes were assessed at 2 and 3.5 years of age using the Ages and Stages Questionnaire, third edition (ASQ-3), which consists of questions on five developmental domains. We performed a multivariate logistic regression analysis of the association between infertility treatment (including ovulation induction (OI), artificial insemination with husband’s sperm (AIH) and assisted reproductive technology (ART)) and the clinical range of ASQ-3.ResultsOf 9655 mother–child pairs, 273 (2.8%) and 487 (5.0%) were conceived through OI/AIH and ART, respectively. The odds of having developmental delays at 2 years of age were higher in children conceived through OI/AIH (OR, 1.36; 95% CI 1.00 to 1.85) and ART (OR, 1.36; 95% CI 1.07 to 1.72) than in those conceived naturally. Additionally, OI/AIH and ART were significantly associated with communication (OR, 1.93; 95% CI 1.25 to 2.98) and gross motor (OR, 1.50; 95% CI 1.08 to 2.09) delays, respectively. There were no statistically significant differences in the odds of having developmental delays at 3.5 years of age in children conceived through OI/AIH (OR, 1.13; 95% CI 0.79 to 1.61) and ART (OR, 1.03; 95% CI 0.78 to 1.37).ConclusionIn this study, we found a significant association between infertility treatment and children’s neurodevelopment at 2 years of age, whereas no statistically significant differences were found at 3.5 years of age.

IntroductionCerebral visual impairment (CVI) refers to a spectrum of brain-related vision problems. CVI is associated with poor educational and mental health outcomes. An intervention has been developed to help children with CVI, involving input from clinicians, teachers and parents. The effectiveness of this intervention needs to be evaluated. This study aims to guide any refinements to the intervention or the design of a future cluster-randomised trial that may be needed.Methods and analysisThis study will include all methods anticipated for a future cluster-randomised controlled trial. Eight primary schools will be recruited and randomised to receive the intervention or carry on with usual practice. The intervention will comprise an information pack for schools and access to a local paediatric ophthalmology clinic (who are prepared to assess them for CVI), for up to 5% of participating children. Outcome assessments will be carried out at baseline (before randomisation) and after 4–5 months of intervention period. Assessments will include children’s self-reported quality of life, their learning ability and behaviour as reported by teachers, and family functioning reported by parents. Cost data will include service use, family expenditure on additional support (eg, private appointments and administration) and school spending and resource used in helping children with special educational needs or disability. A process evaluation (PE) will collect additional data relating to the implementation of the intervention and the trial processes, in the school and clinic settings. The protocol for the PE will be reported separately.Ethics and disseminationEthical permission was obtained from the University of Bristol Faculty of Health Sciences Ethical Committee. The results will inform the design of a future trial to assess the effectiveness and cost-effectiveness of the intervention and will be shared with participants, CVI-support groups and peer-viewed journals.Trial registration numberISRCTN13762177; Pre-results.

IntroductionBrain-related visual impairments, also known as cerebral visual impairment (CVI), are related to damage or poor function in the vision-related areas of the brain. There is broad agreement that CVI is an appropriate term to describe visual impairments that are not accounted by disorders of the eye or optic nerve, but differences remain as to which impairments can be included in this term. The CVI project is a programme of work that includes the development of a complex intervention to share knowledge with teachers, so that they can make both targeted and universal changes to support children with CVI. A feasibility study for a cluster-randomised controlled trial to evaluate this intervention is underway. This paper describes the protocol for an accompanying process evaluation to explore how the intervention is implemented and provide context for the interpretation of the feasibility trial outcomes.Methods and analysisA logic model has been developed to guide data collection. Both qualitative and quantitative data will be collected to assess the feasibility and acceptability of the intervention, the study design and explore how any changes that occur are brought about. Interviews with key primary school staff and parents will investigate responses to the intervention and trial processes. Surveys will collect data on intervention implementation and knowledge of CVI. Photographs of classroom walls will document any changes to visual clutter and document analysis will look for changes to school special educational needs and disability (SEND) policies.Ethics and disseminationEthical approval was granted by the University of Bristol Faculty of Health Sciences Ethics Committee. Findings will contribute to the development of a full-scale cluster-randomised controlled trial to assess the effectiveness of the intervention with adequate statistical power. The results will also support the refinement of the intervention and its underlying theory.

IntroductionDuring the last trimester of pregnancy, the fetal brain undergoes a rapid growth spurt and accumulates essential nutrients including docosahexaenoic acid (DHA). This takes place ex-utero for infants born <29 weeks’ gestation, without the in-utero provisions of DHA. Infants born <29 weeks’ are more likely to experience behavioural and emotional difficulties than their term-born counterparts. It has been hypothesised that supplementing preterm infants with dietary DHA may alleviate insufficiency and subsequently prevent or minimise behavioural problems. This protocol describes a follow-up of infants born <29 weeks gestation who were enrolled in a randomised controlled trial (RCT) of DHA supplementation. We aim to determine whether DHA supplementation improves the behaviour, and general health of these infants.Methods and analysisInfants born <29 weeks’ gestation were enrolled in a multicentre blinded RCT of enteral DHA supplementation. Infants were randomised to receive an enteral emulsion that provided 60 mg/kg/day of DHA or a control emulsion commenced within the first 3 days of enteral feeding, until 36 weeks’ postmenstrual age or discharge home, whichever occurred first. Families of surviving children (excluding those who withdrew from the study) from the Australian sites (up to 955) will be invited to complete a survey. The survey will include questions regarding child behavioural and emotional functioning, executive functioning, respiratory health and general health. We hypothesise that the DHA intervention will have a benefit on the primary outcome, parent-rated behaviour and emotional status as measured using the Total Difficulties score of the Strengths and Difficulties Questionnaire. Detecting a 2-point difference between groups (small effect size of 0.25 SD) with 90% power will require follow-up of 676 participants.Ethics and disseminationThe Women’s and Children Health Network Human Research Ethics Committee reviewed and approved the study (HREC/16/WCHN/184). Results will be disseminated in peer-reviewed publications and conference presentations.Trial registration numberACTRN12612000503820.

ObjectivesTo retrospectively evaluate ophthalmological and neurological outcomes in a Swedish cohort of infants born before 24 weeks gestational age (GA) and explore risk factors for visual impairment.SettingEye and paediatric clinics in Sweden.ParticipantsInfants screened for retinopathy of prematurity (ROP) (n=399), born before 24 weeks GA, 2007–2018. Cases were excluded if ophthalmological follow-up records could not be traced.Primary and secondary outcome measuresPrimary outcomes were ophthalmological, including visual acuity (VA), refractive error, strabismus, nystagmus and cerebral visual impairment (CVI). Secondary outcomes comprised neonatal and neurological morbidities. Data were retrospectively retrieved from medical records.ResultsThe 355 assessed children had a median GA of 23 weeks and 2 days and a median birth weight of 565 g. At the last available ophthalmological examination, the median age was 4.8 years (range 0.5–13.2 years). Nystagmus was recorded in 21.1%, strabismus in 34.8%, and 51.0% wore spectacles. Seventy-three of 333 (21.9%) were visually impaired, defined as being referred to a low vision clinic and/or having a VA less than 20/60 at 3.5 years of age or older. ROP treatment was a significant risk factor for visual impairment (OR 2.244, p=0.003). Visually impaired children, compared with children without visual impairment, more often had neurological deficits such as intellectual disability 63.8% versus 33.3% (p<0.001), epilepsy 21.1% versus 7.5% (p=0.001) and autism spectrum disorders 32.8% versus 20.9% (p=0.043). Nine of the 355 children had been diagnosed with CVI.ConclusionsChildren born before 24 weeks GA frequently had visual impairment in association with neurological deficits. CVI was rarely diagnosed. A multidisciplinary approach for the evaluation and habilitation of these vulnerable infants is warranted. National follow-up guidelines need to be developed and implemented.

IntroductionThe National Health Service (NHS) Long-Term Plan (2019) acknowledges that children and young people with suspected autism wait too long for diagnostic assessment and sets out to reduce waiting times. However, diagnostic pathways vary with limited evidence on what model works best, for whom and in what circumstances. The National Autism Plan for Children (2003) recommended that assessment should be completed within 13 weeks but referral to diagnosis can take as long as 799 days.This Rapid Realist Review (RRR) is the first work package in a national programme of research: a Realist Evaluation of Autism ServiCe Delivery (RE-ASCeD). We explore how particular approaches may deliver high-quality and timely autism diagnostic services for children with possible autism; high quality is defined as compliant with National Institute for Heath and Care Excellence (2011) guidelines, and timely as a pathway lasting no more than one calendar year, based on previous work.Methods and analysisRRR is a well-established approach to synthesising evidence within a compressed timeframe to identify models of service delivery leading to desired outcomes. RRR works backwards from intended outcomes, identified by NICE guidelines and the NHS England Long-Term Plan. The focus is a clearly defined intervention (the diagnostic pathway), associated with specific outcomes (high quality and timely), within a particular set of parameters (Autism and Child & Adolescent Mental Health services in the UK). Our Expert Stakeholder Group consists of policymakers, content experts and knowledge users with a wide range of experience to supplement, tailor and expedite the process. The RRR is consistent with Realist And Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) and includes identifying the research question, searching for information, quality appraisal, data extraction, synthesising the evidence, validation of findings with experts and dissemination.Ethics and disseminationEthical approval not required. Findings will inform the wider RE-ASCeD evaluation and be reported to NHS England.Trial registration numberNCT04422483. This protocol relates to Pre-results.

Childhood socio-economic status (SES), a measure of the availability of material and social resources, is one of the strongest predictors of lifelong well-being. Here we review evidence that experiences associated with childhood SES affect not only the outcome but also the pace of brain development. We argue that higher childhood SES is associated with protracted structural brain development and a prolonged trajectory of functional network segregation, ultimately leading to more efficient cortical networks in adulthood. We hypothesize that greater exposure to chronic stress accelerates brain maturation, whereas greater access to novel positive experiences decelerates maturation. We discuss the impact of variation in the pace of brain development on plasticity and learning. We provide a generative theoretical framework to catalyse future basic science and translational research on environmental influences on brain development.Evidence suggests that socio-economic status can affect not only the outcome of structural and functional development of the brain but also its rate. Tooley, Bassett and Mackey review this evidence and suggest that the valence and frequency of early experiences interact to influence brain development.

Almost 60 years have passed since the initial discovery by Hubel and Wiesel that changes in neuronal activity can elicit developmental rewiring of the central nervous system (CNS). Over this period, we have gained a more comprehensive picture of how both spontaneous neural activity and sensory experience-induced changes in neuronal activity guide CNS circuit development. Here we review activity-dependent synaptic pruning in the mammalian CNS, which we define as the removal of a subset of synapses, while others are maintained, in response to changes in neural activity in the developing nervous system. We discuss the mounting evidence that immune and cell-death molecules are important mechanistic links by which changes in neural activity guide the pruning of specific synapses, emphasizing the role of glial cells in this process. Finally, we discuss how these developmental pruning programmes may go awry in neurodevelopmental disorders of the human CNS, focusing on autism spectrum disorder and schizophrenia. Together, our aim is to give an overview of how the field of activity-dependent pruning research has evolved, led to exciting new questions and guided the identification of new, therapeutically relevant mechanisms that result in aberrant circuit development in neurodevelopmental disorders.Neural circuits in the mammalian central nervous system are modified in response to neural activity during development. In this Review, Faust and colleagues provide an overview of the mechanisms underlying developmental synaptic pruning and how alterations in this process can occur in neurodevelopmental disorders such as autism spectrum disorder and schizophrenia.