Parent screening questionnaires to detect cognitive and language delay at 2 years in high-risk infants: an analysis from the Victorian Infant Collaborative Study 2016-2017 cohort.

OBJECTIVE: To determine the accuracy of two developmental screening questionnaires to detect cognitive or language delay, defined using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III), in children born extremely preterm (EP: <28 weeks' gestation) or extremely low birth weight (ELBW: <1000 g). DESIGN: Prospective cohort study. SETTING: State of Victoria, Australia. PATIENTS: 211 infants born EP/ELBW assessed at 2 years' corrected age (mean 2.2, SD 0.2). MAIN OUTCOME MEASURES: Cognitive and language delay (<-1 SD) on the Bayley-III. The screening questionnaires were the Parent Report of Children's Abilities-Revised (PARCA-R) and the Ages & Stages Questionnaires Third Edition (ASQ-3). RESULTS: The PARCA-R performed better than the ASQ-3, but neither questionnaire had substantial agreement with the Bayley-III to detect cognitive delay; kappa (95% CI): PARCA-R 0.43 (0.23, 0.63); ASQ-3 0.15 (-0.05, 0.35); sensitivity (95% CI): PARCA-R 70% (53%, 84%) ASQ-3 62% (47%, 76%); specificity (95% CI): PARCA-R 73% (60%, 84%) ASQ-3 53% (38%, 68%). When both tools were used in combination (below cut-off on at least one assessment), sensitivity increased to 78% (60%, 91%) but specificity fell to 45% (29%, 62%). Similar trends were noted for language delay on the Bayley-III, although kappa values were better than for cognitive delay. CONCLUSIONS: Neither screening questionnaire identified cognitive delay well, but both were better at identifying language delay. The PARCA-R detects delay on the Bayley-III more accurately than the ASQ-3. Sensitivity for detecting delay is greatest when the PARCA-R and ASQ-3 were used in combination, but resulted in lower specificity.

Unravelling shared mechanisms: insights from recent ME/CFS research to illuminate long COVID pathologies.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic illness often triggered by an initiating acute event, mainly viral infections. The transition from acute to chronic disease remains unknown, but interest in this phenomenon has escalated since the COVID-19 pandemic and the post-COVID-19 illness, termed 'long COVID' (LC). Both ME/CFS and LC share many clinical similarities. Here, we present recent findings in ME/CFS research focussing on proposed disease pathologies shared with LC. Understanding these disease pathologies and how they influence each other is key to developing effective therapeutics and diagnostic tests. Given that ME/CFS typically has a longer disease duration compared with LC, with symptoms and pathologies evolving over time, ME/CFS may provide insights into the future progression of LC.

Hypothalamus volumes in adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): impact of self-reported fatigue and illness duration.

Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex illness of unknown aetiology. Emerging theories suggest ME/CFS may reflect a progressive, aberrant state of homeostasis caused by disturbances within the hypothalamus, yet few studies have investigated this using magnetic resonance imaging in adolescents with ME/CFS. We conducted a volumetric analysis to investigate whether whole and regional hypothalamus volumes in adolescents with ME/CFS differed compared to healthy controls, and whether these volumes were associated with fatigue severity and illness duration. 48 adolescents (25 ME/CFS, 23 controls) were recruited. Lateralised whole and regional hypothalamus volumes, including the anterior-superior, superior tubular, posterior, anterior-inferior and inferior tubular subregions, were calculated from T1-weighted images. When controlling for age, sex and intracranial volume, Bayesian linear regression models revealed no evidence for differences in hypothalamus volumes between groups. However, in the ME/CFS group, a weak linear relationship between increased right anterior-superior volumes and fatigue severity was identified, which was absent in controls. In addition, Bayesian quantile regression revealed a likely-positive association between illness duration and right superior tubular volumes in the ME/CFS group. While these findings suggest overall comparability in regional and whole hypothalamus volumes between adolescents with ME/CFS and controls, preliminary evidence was identified to suggest greater fatigue severity and longer illness duration were associated with greater right anterior-superior and superior-tubular volumes, respectively. These regions contain the anterior and superior divisions of the paraventricular nucleus, involved in the neuroendocrine response to stress, suggesting involvement in ME/CFS pathophysiology. However, replication in a larger, longitudinal cohort is required.

What lies beneath: White matter microstructure in pediatric myalgic encephalomyelitis/chronic fatigue syndrome using diffusion MRI.

Recent studies in adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggest that changes in brain white matter microstructural organization may correlate with core ME/CFS symptoms, and represent a potential biomarker of disease. However, this has yet to be investigated in the pediatric ME/CFS population. We examined group differences in macrostructural and microstructural white matter properties, and their relationship with clinical measures, between adolescents recently diagnosed with ME/CFS and healthy controls. Forty-eight adolescents (25 ME/CFS, 23 controls, mean age 16 years) underwent brain diffusion MRI, and a robust multi-analytic approach was used to evaluate white and gray matter volume, regional brain volume, cortical thickness, fractional anisotropy, mean/axial/radial diffusivity, neurite dispersion and density, fiber density, and fiber cross section. From a clinical perspective, adolescents with ME/CFS showed greater fatigue and pain, poorer sleep quality, and poorer performance on cognitive measures of processing speed and sustained attention compared with controls. However, no significant group differences in white matter properties were observed, with the exception of greater white matter fiber cross section of the left inferior longitudinal fasciculus in the ME/CFS group compared with controls, which did not survive correction for intracranial volume. Overall, our findings suggest that white matter abnormalities may not be predominant in pediatric ME/CFS in the early stages following diagnosis. The discrepancy between our null findings and white matter abnormalities identified in the adult ME/CFS literature could suggest that older age and/or longer illness duration influence changes in brain structure and brain-behavior relationships that are not yet established in adolescence.

Diagnostic accuracy of small-for-gestational-age status for infant mortality and school-age outcomes of live births <28 weeks' gestation: a cohort study.

OBJECTIVES: To determine the diagnostic accuracy of small-for-gestational-age (SGA; <10th centile) status for infant mortality and adverse school-age outcomes in infants born extremely preterm (EP; <28 weeks' gestation). DESIGN: Geographical cohort studies. SETTING: The state of Victoria, Australia. PATIENTS: For mortality, live births 22-27 weeks' gestation from 2009 to 2017 offered active care after birth. For school-age outcomes, survivors to 8 years' corrected age born in 1991-1992, 1997 or 2005. EXPOSURES: SGA <10th centile on four commonly used growth references: three derived from neonatal data (Fenton, UK-WHO and Intergrowth Newborn Size) and one from fetal data (Intergrowth Estimated Fetal Weight). MAIN OUTCOME MEASURES: (a) Infant mortality; (b) major neurodevelopmental disability, and poor performance on tests of IQ, academic achievement, motor function, and executive function. RESULTS: Infant mortality data were available for 2040 infants, and neurodevelopmental data for 499 children. Diagnostic accuracy of SGA status was low overall and varied with the growth reference. Positive predictive values for infant mortality ranged from 18% to 21%, only marginally higher than its 18% prevalence. Compared with a prevalence of 17%, positive predictive values for major neurodevelopmental disability ranged from 30% to 38% for the neonatal growth references but was only 20% for Intergrowth Estimated Fetal Weight. SGA status was also associated with lower IQ, poor academic achievement and poor motor performance. CONCLUSIONS: Among infants born EP, the diagnostic accuracy of SGA status was low for both infant mortality and adverse neurodevelopmental outcomes at school age, but importantly varied with the growth reference used to identify SGA status.

Postnatal corticosteroids and developmental outcomes in extremely preterm or extremely low birth weight infants: The Victorian Infant Collaborative Study 2016-17 cohort.

AIM: Systemic postnatal corticosteroids are used to treat or prevent bronchopulmonary dysplasia (BPD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants but are associated with long-term harm. We aimed to assess the relationship between cumulative postnatal corticosteroid dose and neurodevelopmental outcomes. METHODS: Longitudinal cohort study of all EP/ELBW livebirths in Victoria, Australia 2016-2017. Perinatal data were collected prospectively. Neurodevelopmental assessment was performed at 2 years' corrected age. Linear and logistic regression were used to determine relationships between cumulative corticosteroid dose and neurodevelopment, adjusted for gestational age, birth weight, sex and major intraventricular haemorrhage. RESULTS: Seventy-six EP/ELBW infants received postnatal corticosteroids to treat or prevent BPD, 62/65 survivors were seen at 2 years. Median (IQR) cumulative postnatal corticosteroid dose was 1.36 (0.92-3.45) mg/kg dexamethasone equivalent. Higher cumulative corticosteroid dose was associated with increased odds of cerebral palsy, adjusted OR (95% CI) 1.47 (1.04, 2.07). Higher cumulative corticosteroid dose was also associated with lower cognitive and motor developmental scores, however, this weakened after adjustment for confounding variables: cognitive composite score adjusted coefficient (95% CI) -1.3 (-2.7, 0.1) and motor composite score adjusted coefficient (95% CI) -1.3 (-2.8, 0.2). CONCLUSION: Higher cumulative postnatal corticosteroid dose in EP/ELBW infants is associated with increased odds of cerebral palsy at 2 years' corrected age. Adequately powered studies are needed to assess the independent effects of cumulative steroid dose on neurodevelopmental outcomes.

Spatiotemporal gait variables and step-to-step variability in preschool-aged children born < 30 weeks' gestation and at term in preferred speed, dual-task paradigm, and tandem walking.

BACKGROUND: Children born very preterm (< 32 weeks' gestation) are at greater risk of motor impairment and executive/attentional dysfunctions than term-born children; however, little is known about how functional tasks, including walking, may be affected by very preterm birth. RESEARCH QUESTION: How does the gait pattern of preschool-age children born < 30 weeks compare with term-born controls under a variety of walking conditions? METHODS: In this prospective cohort study, children born < 30 weeks and at term were assessed at 4.5-5 years' corrected age, blinded to birth group. Four walking conditions were assessed using the GAITRite® system: preferred speed, cognitive dual-task, motor dual-task, and tandem walking. Gait variables analysed included speed, cadence, step length, step time, base of support (BOS), and single and double support time. Spatiotemporal variables were compared between groups using linear regression, adjusting for lower-limb length, corrected age at assessment, and number of trials. RESULTS: 224 children (112 < 30 weeks and 112 term-born) were assessed. Gait variables of children born < 30 weeks did not differ from their term-born peers when walking at their preferred speed, except for higher BOS variability (mean difference [MD] = 0.19 cm, 95% confidence interval [CI] 0.10, 0.27, p < 0.001). Under the motor dual-task condition, children born < 30 weeks walked faster (MD= 3.06 cm/s, 95% CI 0.14, 5.97, p = 0.040), with a longer step length (MD= 1.10 cm, 95%CI 0.19, 2.01, p = 0.018), and a wider BOS (MD= 0.37 cm, 95%CI 0.06, 0.67, p = 0.019). In cognitive dual-task and tandem conditions, children born < 30 weeks walked with a wider BOS compared with term-born peers (MD= 0.43 cm, 95%CI 0.05, 0.81, p = 0.028; and MD= 0.30 cm, 95%CI 0.09, 0.51, p = 0.005, respectively). SIGNIFICANCE: This research highlights the need to consider the walking performance of preschool-age children born < 30 weeks under challenging conditions, such as dual-task or tandem walking, when assessing gait patterns and planning interventions.

Health, Wellbeing, and Prognosis of Australian Adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Case-Controlled Follow-Up Study.

BACKGROUND: The purpose of this study was to follow-up an Australian cohort of adolescents newly-diagnosed with ME/CFS at a tertiary paediatric ME/CFS clinic and healthy controls over a mean period of two years (range 1-5 years) from diagnosis. Objectives were to (a) examine changes over time in health and psychological wellbeing, (b) track ME/CFS symptomatology and fulfillment of paediatric ME/CFS diagnostic criteria over time, and (c) determine baseline predictors of ME/CFS criteria fulfilment at follow-up. METHODS: 34 participants aged 13-18 years (25 ME/CFS, 23 controls) completed standardised questionnaires at diagnosis (baseline) and follow-up assessing fatigue, sleep quality and hygiene, pain, anxiety, depression, and health-related quality of life. ME/CFS symptomatology and diagnostic criteria fulfilment was also recorded. RESULTS: ME/CFS patients showed significant improvement in most health and psychological wellbeing domains over time, compared with controls who remained relatively stable. However, fatigue, pain, and health-related quality of life remained significantly poorer amongst ME/CFS patients compared with controls at follow-up. Sixty-five percent of ME/CFS patients at baseline continued to fulfil ME/CFS diagnostic criteria at follow-up, with pain the most frequently experienced symptom. Eighty-two percent of patients at follow-up self-reported that they still had ME/CFS, with 79% of these patients fulfilling criteria. No significant baseline predictors of ME/CFS criteria fulfilment at follow-up were observed, although pain experienced at baseline was significantly associated with criteria fulfilment at follow-up (R = 0.6, p = 0.02). CONCLUSIONS: The majority of Australian adolescents with ME/CFS continue to fulfil diagnostic criteria at follow-up, with fatigue, pain, and health-related quality of life representing domains particularly relevant to perpetuation of ME/CFS symptoms in the early years following diagnosis. This has direct clinical impact for treating clinicians in providing a more realistic prognosis and highlighting the need for intervention with young people with ME/CFS at the initial diagnosis and start of treatment.

Temporal Trends in Neurodevelopmental Outcomes to 2 Years After Extremely Preterm Birth.

Importance: Survival of infants born extremely preterm (EP) (<28 weeks' gestation) has increased since the early 1990s. It is necessary to know whether increased survival is accompanied by increased neurodevelopmental disability. Objective: To examine changes in major (ie, moderate or severe) neurodevelopmental disability and survival free of major neurodevelopmental disability at 2 years in infants born EP. Design, Setting, and Participants: Four prospective longitudinal cohort studies comprising all EP live births at 22 to 27 weeks' gestation from April 1, 2016, to March 31, 2017, and earlier eras (1991-1992, 1997, and 2005), and contemporaneous term-born controls in the state of Victoria, Australia. Among 1208 live births during the periods studied, data were available for analysis of 2-year outcomes in 1152 children: 422 (1991-1992), 215 (1997), 263 (2005), and 252 (2016-2017). Data analysis was performed from September 17, 2020, to April 15, 2021. Exposures: Extreme preterm live birth. Main Outcomes and Measures: Survival, blindness, deafness, cerebral palsy, developmental delay, and neurodevelopmental disability at 2 years' corrected age. Developmental delay comprised a developmental quotient less than -1 SD relative to the control group means on the Bayley Scales for each era. Major neurodevelopmental disability comprised blindness, deafness, moderate to severe cerebral palsy, or a developmental quotient less than -2 SDs. Individual neurodevelopmental outcomes in each era were contrasted relative to the 2016-2017 cohort using logistic regression adjusted for gestational age, sex, birth weight z score, and sociodemographic variables. Changes in survival free of major neurodevelopmental disability over time were also assessed using logistic regression. Results: Survival to 2 years was highest in 2016-2017 (73% [215 of 293]) compared with earlier eras (1991-1992: 53% [225 of 428]; 1997: 70% [151 of 217]; 2005: 63% [170 of 270]). Blindness and deafness were uncommon (<3%). Cerebral palsy was less common in 2016-2017 (6%) than in earlier eras (1991-1992: 11%; 1997: 12%; 2005: 10%). There were no obvious changes in the rates of developmental quotient less than -2 SDs across eras (1991-1992: 18%; 1997: 22%; 2005: 7%; 2016-2017: 15%) or in rates of major neurodevelopmental disability (1991-1992: 20%; 1997: 26%; 2005: 15%; 2016-2017: 15%). Rates of survival free of major neurodevelopmental disability increased steadily over time: 42% (1991-1992), 51% (1997), 53% (2005), and 62% (2016-2017) (odds ratio, 1.30; 95% CI, 1.15-1.48 per decade; P < .001). Conclusions and Relevance: These findings suggest that survival free of major disability at age 2 years in children born EP has increased by an absolute 20% since the early 1990s. Increased survival has not been associated with increased neurodevelopmental disability.

Investigating the brain structural connectome following working memory training in children born extremely preterm or extremely low birth weight.

Children born extremely preterm (EP, <28 weeks' gestation) or extremely low birth weight (ELBW, <1,000 g) are a vulnerable population at high risk of working memory impairments. We aimed to examine changes in the brain structural connectivity networks thought to underlie working memory performance, after completion of a working memory training program (Cogmed) compared with a placebo program in EP/ELBW children. This was a double-blind, placebo-controlled randomized trial (the Improving Memory in a Preterm Randomised Intervention Trial). Children born EP/ELBW received either the Cogmed or placebo program at 7 years of age (n = 91). A subset of children had magnetic resonance imaging of the brain immediately pre- and 2 weeks post-training (Cogmed n = 28; placebo n = 27). T1 -weighted and diffusion-weighted images were used to perform graph theoretical analysis of structural connectivity networks. Changes from pre-training to post-training in structural connectivity metrics were generally similar between randomized groups. There was little evidence that changes in structural connectivity metrics were related to changes in working memory performance from pre- to post-training. Overall, our results provide little evidence that the Cogmed working memory training program has training-specific effects on structural connectivity networks in EP/ELBW children.

Resting-state functional connectivity, cognition, and fatigue in response to cognitive exertion: a novel study in adolescents with chronic fatigue syndrome.

Emerging evidence suggests that central nervous system dysfunction may underlie the core symptoms of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in adults, such as cognitive disturbance, fatigue and post-exertional malaise. Research into brain dysfunction in the pediatric CFS/ME context, however, is severely lacking. It is unclear whether the adolescent CFS/ME brain functions differently compared with healthy peers, particularly in situations where significant mental effort is required. This study used resting-state functional MRI in a novel repeated-measures design to evaluate intrinsic connectivity, cognitive function, and subjective fatigue, before and after a period of cognitive exertion in 48 adolescents (25 CFS/ME, 23 healthy controls). Results revealed little evidence for a differential effect of cognitive exertion in CFS/ME compared with controls. Both groups demonstrated a similar rate of reduced intrinsic functional connectivity within the default mode network (DMN), reduced sustained attentional performance, slower processing speed, and increased subjective fatigue as a result of cognitive exertion. However, CFS/ME adolescents consistently displayed higher subjective fatigue, and controls outperformed the CFS/ME group overall on cognitive measures of processing speed, sustained attention and new learning. No brain-behavior relationships were observed between DMN connectivity, cognitive function, and fatigue over time. These findings suggest that effortful cognitive tasks may elicit similar levels of energy expenditure across all individuals in the form of reduced brain functioning and associated fatigue. However, CFS/ME may confer a lower starting threshold from which to access energy reserves and cognitive resources when cognitive effort is required.

Working memory training and brain structure and function in extremely preterm or extremely low birth weight children.

This study in children born extremely preterm (EP; <28 weeks' gestational age) or extremely low birth weight (ELBW; <1,000 g) investigated whether adaptive working memory training using Cogmed® is associated with structural and/or functional brain changes compared with a placebo program. Ninety-one EP/ELBW children were recruited at a mean (standard deviation) age of 7.8 (0.4) years. Children were randomly allocated to Cogmed or placebo (45-min sessions, 5 days a week over 5-7 weeks). A subset had usable magnetic resonance imaging (MRI) data pretraining and 2 weeks posttraining (structural, n = 48; diffusion, n = 43; task-based functional, n = 18). Statistical analyses examined whether cortical morphometry, white matter microstructure and blood oxygenation level-dependent (BOLD) signal during an n-back working memory task changed from pretraining to posttraining in the Cogmed and placebo groups separately. Interaction analyses between time point and group were then performed. There was a significant increase in neurite density in several white matter regions from pretraining to posttraining in both the Cogmed and placebo groups. BOLD signal in the posterior cingulate and precuneus cortices during the n-back task increased from pretraining to posttraining in the Cogmed but not placebo group. Evidence for group-by-time interactions for the MRI measures was weak, suggesting that brain changes generally did not differ between Cogmed and placebo groups. Overall, while some structural and functional MRI changes between the pretraining and posttraining period in EP/ELBW children were observed, there was little evidence of training-induced neuroplasticity, with changes generally identified in both groups. Trial registration Australian New Zealand Clinical Trials Registry, anzctr.org.au; ACTRN12612000124831.

Efficiency of structural connectivity networks relates to intrinsic motivation in children born extremely preterm.

Intrinsic motivation is essential for academic success and cognitive growth, but limited work has examined the neuroanatomical underpinnings of intrinsic motivation from a network perspective, particularly in early childhood. Using graph theoretical analysis, this study investigated global and local properties of structural connectivity networks in relation to intrinsic motivation within a vulnerable group of children at early school age. Fifty-three 7 year-old children born extremely preterm (<28 weeks' gestational age)/extremely low birth weight (<1000 g) underwent T1 and diffusion weighted imaging. Structural connectivity networks were generated using 162 cortical and subcortical nodes, and edges were created using constrained spherical deconvolution-based tractography. Global and node-specific network measures were analyzed in association with self-reported aspects of intrinsic motivation for school learning (Mastery, Challenge and Curiosity) using linear regression. Results indicated that increased information transfer across the network was associated with greater Mastery, while increased clustering and small-world topology related to greater Challenge. Increased efficiency and connection strength of the striatum in particular, related to greater intrinsic motivation. These findings suggest that both integrated and segregated network communication support aspects of intrinsic motivation in childhood, and shed new light on structural network properties important for intrinsic motivation orientations in extremely preterm children at early school age.

Epigenetic Influences on Neurodevelopment at 11 Years of Age: Protocol for the Longitudinal Peri/Postnatal Epigenetic Twins Study at 11 Years of Age (PETS@11).

Neurodevelopment is sensitive to genetic and pre/postnatal environmental influences. These effects are likely mediated by epigenetic factors, yet current knowledge is limited. Longitudinal twin studies can delineate the link between genetic and environmental factors, epigenetic state at birth and neurodevelopment later in childhood. Building upon our study of the Peri/postnatal Epigenetic Twin Study (PETS) from gestation to 6 years of age, here we describe the PETS 11-year follow-up in which we will use neuroimaging and cognitive testing to examine the relationship between early-life environment, epigenetics and neurocognitive outcomes in mid-childhood. Using a within-pair twin model, the primary aims are to (1) identify early-life epigenetic correlates of neurocognitive outcomes; (2) determine the developmental stability of epigenetic effects and (3) identify modifiable environmental risk factors. Secondary aims are to identify factors influencing gut microbiota between 6 and 11 years of age to investigate links between gut microbiota and neurodevelopmental outcomes in mid-childhood. Approximately 210 twin pairs will undergo an assessment at 11 years of age. This includes a direct child cognitive assessment, multimodal magnetic resonance imaging, biological sampling, anthropometric measurements and a range of questionnaires on health and development, behavior, dietary habits and sleeping patterns. Data from complementary data sources, including the National Assessment Program - Literacy and Numeracy and the Australian Early Development Census, will also be sought. Following on from our previous focus on relationships between growth, cardiovascular health and oral health, this next phase of PETS will significantly advance our understanding of the environmental interactions that shape the developing brain.

Long-Term Academic Functioning Following Cogmed Working Memory Training for Children Born Extremely Preterm: A Randomized Controlled Trial.

OBJECTIVE: To assess the effectiveness of Cogmed Working Memory Training compared with a placebo program in improving academic functioning 24 months post-training in extremely preterm/extremely low birth weight 7-year-olds. STUDY DESIGN: A multicenter double-blind, placebo-controlled randomized controlled trial was conducted across all tertiary neonatal hospitals in the state of Victoria, Australia. Participants were 91 extremely preterm/extremely low birth weight 7-year-old children born in Victoria in 2005. Children were randomly assigned to either the Cogmed or placebo arm and completed the Cogmed or placebo program (20-25 sessions of 35-40 minutes duration) at home over 5-7 weeks. Academic achievement (word reading, spelling, sentence comprehension, and mathematics) was assessed 24 months post-training, as well as at 2 weeks and 12 months post-training, via standardized testing inclusive of working memory, attention, and executive behavior assessments. Data were analyzed using an intention-to-treat approach with mixed-effects modeling. RESULTS: There was little evidence of any benefits of Cogmed on academic functioning 24 months post-training, as well as on working memory, attention, or executive behavior at any age up to 24 months post-training compared with the placebo program. CONCLUSIONS: We currently do not recommend administration of Cogmed for early school-aged children born extremely preterm/extremely low birth weight to improve academic functioning. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12612000124831.

Sleep Quality in Adolescents With Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME).

STUDY OBJECTIVES: Little is known about the type and severity of sleep disturbances in the pediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) population, compared with healthy adolescents. Using a range of objective and subjective measures, the aim of this study was to investigate sleep quality, the relationship between objective and subjective measures of sleep quality, and their associations with anxiety in adolescents with CFS/ME compared with healthy controls. METHODS: Twenty-one adolescents with CFS/ME aged 13 to 18 years (mean age 15.57 ± 1.40), and 145 healthy adolescents aged 13 to 18 years (mean age 16.2 ± 1.00) wore actigraphy watches continuously for 2 weeks to collect a number of objective sleep variables. The Pittsburgh Sleep Quality Index was used to obtain a subjective measure of sleep quality. Anxiety was measured by the Spence Children's Anxiety scale. RESULTS: On average over the 2-week period, adolescents with CFS/ME were found to have (1) significantly longer objective sleep onset latency, time in bed, total sleep time, and a later rise time (all P < .005), and (2) significantly poorer subjective sleep quality (P < .001), compared with healthy adolescents. The CFS/ME patient group displayed higher levels of anxiety (P < .05), and in both groups, higher levels of anxiety were significantly related to poorer subjective sleep quality (P < .001). CONCLUSIONS: This study provides objective and subjective evidence of sleep disturbance in adolescents with CFS/ME compared with healthy adolescent controls.

Motor trajectories from birth to 5 years of children born at less than 30 weeks' gestation: early predictors and functional implications. Protocol for a prospective cohort study.

INTRODUCTION: Motor impairments are one of the most frequently reported adverse neurodevelopmental consequences in children born < 30 weeks' gestation. Up to 15% of children born at < 30 weeks have cerebral palsy and an additional 50% have mild to severe motor impairment at school age. The first 5 years of life are critical for the development of fundamental motor skills. These skills form the basis for more complex skills that are required to competently and confidently participate in schooling, sporting and recreational activities. In children born at < 30 weeks' gestation, the trajectory of motor development from birth to 5 years is not fully understood. The neural alterations that underpin motor impairments in these children are also unclear. It is essential to determine if early clinical evaluations and neuroimaging biomarkers can predict later motor impairment and associated functional problems at 5 years of age. This will help to identify children who will benefit the most from early intervention and improve functional outcomes at school age. RESEARCH AIMS: The primary aim of this study is to compare the prevalence of motor impairment from birth to 5 years of age between children born at < 30 weeks and term-born controls, and to determine whether persistent abnormal motor assessments in the newborn period in those born at < 30 weeks predict abnormal motor functioning at 5 years of age. Secondary aims for children born at < 30 weeks and term-born children are: 1) to determine whether novel early magnetic resonance imaging-based structural or functional biomarkers that can predict motor impairments at 5 years are detectable in the neonatal period; 2) to investigate the association between motor impairments and concurrent deficits in body structure and function at 5 years of age; and 3) to explore how motor impairments at 5 years (including abnormalities of gait, postural control and strength) are associated with concurrent functional outcomes, including physical activity, cognitive ability, learning ability, and behavioural and emotional problems. DESIGN: Prospective longitudinal cohort study. PARTICIPANTS AND SETTING: 150 preterm children (born at < 30 weeks' gestation) and 151 term-born children (born at > 36 completed weeks' gestation and weighing > 2499g) admitted to the Royal Women's Hospital, Melbourne, were recruited at birth and will be invited to participate in a 5-year follow-up study. PROCEDURE: This study will examine previously collected data (from birth to 2 years) that comprise detailed motor assessments, and structural and functional brain MRI images. At 5 years, preterm and term, children will be examined using comprehensive motor assessments, including: the Movement Assessment Battery for Children (2nd edition) and measures of gait function through spatiotemporal (assessed with the GAITRite® Walkway) and dynamic postural control (assessed with Microsoft Kinect) variables; and hand grip strength (assessed with a dynamometer); and measures of physical activity (assessed using accelerometry), cognitive development (assessed with Wechsler Preschool and Primary Scale of Intelligence), and emotional and behavioural status (assessed with the Strengths and Difficulties Questionnaire and the Developmental and Wellbeing Assessment). At the 5-year assessment, parents/caregivers will be asked to complete questionnaires on demographics, physical activity, activities of daily living, behaviour, additional therapy (eg, physiotherapy and occupational therapy), and motor function (assessed with Pediatric Evaluation of Disability Inventory, Pediatric Quality of Life Questionnaire, the Little Developmental Co-ordination Questionnaire and an activity diary). ANALYSIS: For the primary aim, the prevalence of motor impairment from birth to 5 years will be compared between children born at < 30 weeks and at term, using the proportion of children classified as abnormal at each of the time points (term age, 1, 2 and 5 years). Persistent motor impairments during the neonatal period will be assessed as a predictor of severity of motor impairment at 5 years of age in children born < 30 weeks using linear regression. Models will be fitted using generalised estimating equations to allow for the clustering of multiple births. Analysis will be repeated with adjustment for predictors of motor outcome, including additional therapy, sex, brain injury and chronic lung disease. DISCUSSION/SIGNIFICANCE: Understanding the developmental precursors of motor impairment in children born before 30 weeks is essential for limiting disruption to skill development, and potential secondary impacts on physical activity, participation, academic achievement, self-esteem and associated outcomes (such as obesity, poor physical fitness and social isolation). An improved understanding of motor skill development will enable targeting of interventions and streamlining of services to children at highest risk of motor impairments.

Preventing academic difficulties in preterm children: a randomised controlled trial of an adaptive working memory training intervention - IMPRINT study.

BACKGROUND: Very preterm children exhibit difficulties in working memory, a key cognitive ability vital to learning information and the development of academic skills. Previous research suggests that an adaptive working memory training intervention (Cogmed) may improve working memory and other cognitive and behavioural domains, although further randomised controlled trials employing long-term outcomes are needed, and with populations at risk for working memory deficits, such as children born preterm.In a cohort of extremely preterm (<28 weeks' gestation)/extremely low birthweight (<1000 g) 7-year-olds, we will assess the effectiveness of Cogmed in improving academic functioning 2 years' post-intervention. Secondary objectives are to assess the effectiveness of Cogmed in improving working memory and attention 2 weeks', 12 months' and 24 months' post-intervention, and to investigate training related neuroplasticity in working memory neural networks 2 weeks' post-intervention. METHODS/DESIGN: This double-blind, placebo-controlled, randomised controlled trial aims to recruit 126 extremely preterm/extremely low birthweight 7-year-old children. Children attending mainstream school without major intellectual, sensory or physical impairments will be eligible. Participating children will undergo an extensive baseline cognitive assessment before being randomised to either an adaptive or placebo (non-adaptive) version of Cogmed. Cogmed is a computerised working memory training program consisting of 25 sessions completed over a 5 to 7 week period. Each training session takes approximately 35 minutes and will be completed in the child's home. Structural, diffusion and functional Magnetic Resonance Imaging, which is optional for participants, will be completed prior to and 2 weeks following the training period. Follow-up assessments focusing on academic skills (primary outcome), working memory and attention (secondary outcomes) will be conducted at 2 weeks', 12 months' and 24 months' post-intervention. DISCUSSION: To our knowledge, this study will be the first randomised controlled trial to (a) assess the effectiveness of Cogmed in school-aged extremely preterm/extremely low birthweight children, while incorporating advanced imaging techniques to investigate neural changes associated with adaptive working memory training, and (b) employ long-term follow-up to assess the potential benefit of improved working memory on academic functioning. If effective, Cogmed would serve as a valuable, available intervention for improving developmental outcomes for this population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000124831.

Left of centre: asymmetries for the horizontal vertical line illusion.

This study explored the mechanisms that underlie asymmetries for the horizontal vertical illusion (HVI), which deceives length perception, so that a vertical line is perceived as longer than a horizontal line of equivalent length. In Experiment 1, university students (n = 14) made length judgements for vertical and horizontal lines. The vertical line was shifted in eight steps from the far left of the horizontal line (⌊) to the far right (⌋). An HVI was observed for the medial positions (⊥), which diminished towards the lateral positions. The HVI was also stronger when the vertical line was on the left. Because the left/right asymmetry changed as a function of lateral/medial position, the asymmetry within the HVI stimulus is most likely the result of pseudoneglect, which affects judgements of horizontal length. In Experiment 2, participants (n = 15) made judgements for HVI stimuli presented to the left- and right-hemispace and the midline. The HVI was stronger in the left hemispace. Because the asymmetry between the left- and right-hemispaces did not interact with the asymmetry within the stimuli, it was concluded that the asymmetry between hemispatial positions was the result of right hemisphere susceptibility to illusory geometrical effects whereas the asymmetry within the stimulus is related to an object-centred attentional asymmetry. The HVI is affected by asymmetries in length judgements and susceptibility to illusions and may provide interesting insights into attentional disorders in clinical populations, such as neglect.