ORCID Profile
0000-0002-4686-6331
Current Organisations
Murdoch Children's Research Institute
,
Mercy Health
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Publisher: Wiley
Date: 23-02-2021
DOI: 10.1002/JNR.24818
Abstract: Children born extremely preterm (EP, weeks’ gestation) or extremely low birth weight (ELBW, ,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). T 1 ‐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.
Publisher: BMJ
Date: 09-2020
DOI: 10.1136/BMJOPEN-2020-037507
Abstract: It is unclear how newer methods of respiratory support for infants born extremely preterm (EP 22–27 weeks gestation) have affected in-hospital sequelae. We aimed to determine changes in respiratory support, survival and morbidity in EP infants since the early 1990s. Prospective longitudinal cohort study. The State of Victoria, Australia. All EP births offered intensive care in four discrete eras (1991–1992 (24 months): n=332, 1997 (12 months): n=190, 2005 (12 months): n=229, and April 2016–March 2017 (12 months): n=250). Consumption of respiratory support, survival and morbidity to discharge home. Cost-effectiveness ratios describing the average additional days of respiratory support associated per additional survivor were calculated. Median duration of any respiratory support increased from 22 days (1991–1992) to 66 days (2016–2017). The increase occurred in non-invasive respiratory support (2 days (1991–1992) to 51 days (2016–2017)), with high-flow nasal cannulae, unavailable in earlier cohorts, comprising almost one-half of the duration in 2016–2017. Survival to discharge home increased (68% (1991–1992) to 87% (2016–2017)). Cystic periventricular leukomalacia decreased (6.3% (1991–1992) to 1.2% (2016–2017)), whereas retinopathy of prematurity requiring treatment increased (4.0% (1991–1992) to 10.0% (2016–2017)). The average additional costs associated with one additional infant surviving in 2016–2017 were 200 (95% CI 150 to 297) days, 326 (183 to 1127) days and 130 (70 to 267) days compared with 1991–1992, 1997 and 2005, respectively. Consumption of resources for respiratory support has escalated with improved survival over time. Cystic periventricular leukomalacia reduced in incidence but retinopathy of prematurity requiring treatment increased. How these changes translate into long-term respiratory or neurological function remains to be determined.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.JPHYS.2016.07.002
Abstract: 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. 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. Prospective longitudinal cohort study. 150 preterm 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. 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). 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. 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.
Publisher: Elsevier BV
Date: 05-2023
Publisher: Wiley
Date: 18-06-2023
DOI: 10.1002/JNR.25223
Abstract: 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.
Publisher: Wiley
Date: 12-11-2019
DOI: 10.1002/HBM.24832
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2020
DOI: 10.1161/HYPERTENSIONAHA.120.15786
Abstract: Being born extremely preterm (EP weeks’ gestation) or extremely low birthweight (ELBW g birthweight) may predict increased cardiometabolic risk in adulthood, but other early life predictors are less well described. We aimed to (1) compare cardiovascular health profiles between 165 adults born EP/ELBW and 127 controls at age 25 years, drawn from a prospective longitudinal cohort study, recruited at birth in 1991 to 1992 and (2) in the EP/ELBW group, determine early life associations of cardiovascular health. Cardiovascular health profiles were calculated in idually for measures of anthropometry, abdominal visceral fat, blood pressure, fasting plasma glucose, insulin, lipids, C-reactive protein, vascular indices, exercise tolerance and smoking status, and summed for an overall score. Cardiovascular health profiles were compared between groups using logistic regression (in idual scores) and the Mann-Whitney U test (cumulative score). Compared with controls, adults born EP/ELBW had less favorable cardiovascular health profiles in idually for abdominal visceral fat (odds ratio, 0.56 [95% CI, 0.33–0.96], P =0.03), blood pressure (odds ratio 0.38 [95% CI, 0.23–0.63], P .001), exercise capacity (odds ratio 0.37 [95% CI, 0.22–0.63], P .001), and fasting glucose (odds ratio 0.51 [95% CI, 0.31–0.84], P =0.01) and overall (median [interquartile range] 10 [7–11] versus 11 [9–12], P =0.007). Male sex predicted unfavorable abdominal visceral fat, blood pressure and fasting glucose, and favorable exercise capacity. Greater increases in weight Z scores between 2 and 8, and 8 and 18 years predicted less favorable profiles of exercise capacity and visceral fat. Longer-term follow-up is critical to determine the cardiovascular sequelae of adults born EP/ELBW.
Publisher: Elsevier BV
Date: 08-2023
Publisher: Cold Spring Harbor Laboratory
Date: 23-05-2023
DOI: 10.1101/2023.05.16.23290031
Abstract: 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 revealed no evidence for differences in hypothalamus volumes between groups. However, in the ME/CFS group, a negative linear relationship between right anterior-superior volumes and fatigue severity was identified, which was absent in controls. In addition, Bayesian ordinal 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 and longer illness duration were associated with greater right anterior-superior and superior-tubular volumes, respectively. These regions contain the anterior and superior isions 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.
Publisher: Springer Science and Business Media LLC
Date: 13-09-2019
DOI: 10.1007/S41465-019-00150-7
Abstract: Children born extremely preterm (EP 28 weeks of gestation) or extremely low birth weight (ELBW 1000 g) are at increased risk of working memory deficits compared with their term-born peers and may benefit from working memory training. This study aimed to determine whether Cogmed Working Memory Training®, compared with a placebo training program, was associated with changes in resting-state functional connectivity (rsfc) and whether these changes correlated with working memory performance in EP/ELBW children. Twenty-one 7-year-old EP/ELBW children were enrolled in a double-blinded randomized controlled trial and had magnetic resonance imaging (MRI) assessments (Cogmed, n = 12 placebo (a non-adaptive version of Cogmed), n = 9). Prior to training (baseline) and 2 weeks post-training, all children received a cognitive assessment, inclusive of immediate memory and working memory measures and an MRI. The Cogmed Improvement Index was used as a measure of improvement in trained activities in the Cogmed group. Resting-state functional MRI was used to measure training-related changes in intra- and inter-network rsfc. The networks assessed include the default mode network, the left and right central executive networks, the bilateral executive network, the dorsal attention network, and the salience network. rsfc data were compared between treatment groups and investigated in relation to changes in working memory performance. There was little evidence of differences in intra- or inter-network rsfc strength changes from baseline to post-training between treatment groups. In the Cogmed group, working memory performance was associated with increased rsfc from baseline to post-training within the precuneus network, but not in the placebo group. In the Cogmed group, results that did not survive multiple comparison correction further showed that improvement in trained activities was associated with increased rsfc between the left central and bilateral executive networks, and with decreased rsfc within the right central executive network and between the right central executive and salience networks. Changes in rsfc may facilitate working memory performance following Cogmed training. Further studies are needed to investigate how changes in rsfc are associated with behavioral changes to better support working memory in vulnerable groups.
Publisher: MDPI AG
Date: 16-08-2021
DOI: 10.3390/JCM10163603
Abstract: 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.
Publisher: Springer Science and Business Media LLC
Date: 16-09-2013
Abstract: 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 ( weeks’ gestation)/extremely low birthweight ( 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. 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. 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. Australian New Zealand Clinical Trials Registry ACTRN12612000124831 .
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.GAITPOST.2021.11.027
Abstract: 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. How does the gait pattern of preschool-age children born < 30 weeks compare with term-born controls under a variety of walking conditions? 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. 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). 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.
Publisher: Elsevier BV
Date: 05-2013
Publisher: American Academy of Sleep Medicine (AASM)
Date: 15-09-2017
DOI: 10.5664/JCSM.6722
Publisher: Springer Science and Business Media LLC
Date: 03-06-2019
Publisher: Wiley
Date: 15-02-2023
DOI: 10.1111/APA.16696
Abstract: 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. 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. 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). 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.
Publisher: Springer Science and Business Media LLC
Date: 17-05-2020
DOI: 10.1007/S11682-019-00119-2
Abstract: 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 in iduals 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.
Publisher: Elsevier BV
Date: 05-2018
Publisher: BMJ
Date: 17-02-2021
DOI: 10.1136/ARCHDISCHILD-2020-320582
Abstract: To compare health-related quality of life (HRQOL) at 8 years in children born extremely preterm (EP) with contemporaneous term-born controls over three epochs: 1991–92, 1997 and 2005. Prospective recruitment of geographic cohorts across three distinct eras. Utilities were calculated from the parent-completed Health Utilities Index (HUI), version 2 (1991–92 and 1997 cohorts) and version 3 (2005 cohort). Differences in utilities .05 are clinically important. The state of Victoria, Australia. 475 EP ( weeks’ gestation) and 570 term controls. Utilities of children born EP compared with term controls within each era, and paired differences between an EP and matched controls compared across eras. Overall, 86% of survivors had utility data at 8 years of age 475 EP and 570 controls. In all eras, parent-reported utilities were lower for children born EP compared with controls (difference in medians (95% CIs) 1991–92, −0.053 (–0.071 to –0.035) 1997, –0.053 (−0.072 to –0.034) 2005, –0.082 (−0.097 to –0.068)). Mean differences (MD) between EP children and matched controls within each era were lower in the 2005 cohort compared with both the 1991–92 cohort (MD −0.054, 95% CI −0.097 to –0.010) and the 1997 cohort (MD −0.053, 95% CI −0.097 to –0.009). Children born EP in the postsurfactant era have clinically important reductions in parent-reported HRQOL compared with controls, which may be worsening over time.
Publisher: BMJ
Date: 29-05-2023
DOI: 10.1136/ARCHDISCHILD-2023-325515
Abstract: To determine the diagnostic accuracy of small-for-gestational-age (SGA th centile) status for infant mortality and adverse school-age outcomes in infants born extremely preterm (EP weeks’ gestation). Geographical cohort studies. The state of Victoria, Australia. 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. SGA th 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). (a) Infant mortality (b) major neurodevelopmental disability, and poor performance on tests of IQ, academic achievement, motor function, and executive function. 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. 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.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2023
DOI: 10.1007/S00429-023-02682-3
Abstract: 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 isions 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.
Publisher: Routledge
Date: 28-07-2018
Publisher: Cambridge University Press (CUP)
Date: 12-2019
DOI: 10.1017/THG.2019.120
Abstract: Neurodevelopment is sensitive to genetic and pre ostnatal 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 ostnatal 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 s ling, 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.
Publisher: Wiley
Date: 02-02-2021
DOI: 10.1111/AJO.13301
Abstract: Magnesium sulphate was introduced for fetal neuroprotection in Australia in 2010. The aim of this study was to determine how often antenatal magnesium sulphate is used currently and its association with cerebral palsy in children born weeks' gestation. Participants comprised all survivors born weeks' gestational age in the state of Victoria in 2016‐17, and earlier, in 1991‐92, 1997, 2005. Rates of cerebral palsy, diagnosed at two years for the 2016‐17 cohort, and at eight years in the earlier cohorts, were compared across eras. Within 2016‐17, the proportions of children exposed to antenatal magnesium sulphate were determined, and rates of cerebral palsy were compared between those with and without exposure to magnesium sulphate. Overall, cerebral palsy was present in 6% (11/171) of survivors born in 2016‐17, compared with 12% (62/499) of survivors born in the three earlier eras (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.25–0.94 P = 0.032). Data were available for 213/215 (99%) survivors born in 2016‐17, of whom 147 (69%) received magnesium sulphate. Data on cerebral palsy at two years were available for 171 (80%) survivors with magnesium data. Cerebral palsy was present in 5/125 (4%) children exposed to magnesium sulphate and in 6/46 (13%) of those not exposed (OR 0.28, 95% CI 0.08–0.96 P = 0.043). Antenatal magnesium sulphate is being translated into clinical practice for infants born weeks' gestation, but there is room for improvement. It is associated with lower rates of cerebral palsy in survivors.
Publisher: Springer Science and Business Media LLC
Date: 25-11-2010
DOI: 10.1007/S00426-010-0315-2
Abstract: 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.
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.JPEDS.2018.07.003
Abstract: 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. 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. 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. We currently do not recommend administration of Cogmed for early school-aged children born extremely preterm/extremely low birth weight to improve academic functioning. Australian New Zealand Clinical Trials Registry: ACTRN12612000124831.
Publisher: American Medical Association (AMA)
Date: 10-2021
Publisher: BMJ
Date: 05-2019
DOI: 10.1136/BMJOPEN-2019-030345
Abstract: Infants born extremely preterm (EP, weeks’ gestation) or with extremely low birth weight (ELBW, g) in the era when surfactant has been available clinically are at high risk of health and developmental problems in childhood and adolescence. However, how their health and well-being may be affected in adulthood is not well known. This study aims to compare between EP/ELBW and normal birthweight (NBW) controls: (1) physical health, mental health and socioemotional functioning at 25 years of age and (2) trajectories of these outcomes from childhood to adulthood. In addition, this study aims to identify risk factors in pregnancy, infancy, childhood and adolescence for poor physical health and well-being in EP/ELBW young adults. The Victorian Infant Collaborative Study (VICS) is a prospective geographical cohort of all EP/ELBW survivors to 18 years of age born in the State of Victoria, Australia, from 1 January 1991 to 31 December 1992 (n=297) and contemporaneous term-born/NBW controls (n=262). Participants were recruited at birth and followed up at 2, 5, 8 and 18 years. This 25-year follow-up includes assessments of physical health (cardiovascular, respiratory and musculoskeletal), mental health and socioemotional functioning. Outcomes will be compared between the birth groups using linear and logistic regression, fitted using generalised estimating equations (GEEs). Trajectories of health outcomes from early childhood will be compared between the birth groups using linear mixed-effects models. Risk factors for adult outcomes will be assessed using linear and logistic regression (fitted using GEEs). This study was approved by the Human Research Ethics Committees of the Royal Women’s Hospital, Mercy Hospital for Women, Monash Medical Centre and the Royal Children’s Hospital, Melbourne. Study outcomes will be disseminated through conference presentations, peer-reviewed publications, the internet and social media.
Publisher: Wiley
Date: 12-09-2022
DOI: 10.1111/APA.16098
Abstract: To assess the causal effect of being born extremely preterm (EP weeks’ gestation) or extremely low birthweight (ELBW g), compared with being born at term, on neurodevelopment and social‐emotional development at 2 years’ corrected age. Prospective geographical cohort study of children born EP/ELBW over 12 months in 2016 from Victoria, Australia, and term‐born controls. Children were assessed at 2 years’ corrected age with the Bayley Scales of Infant and Toddler Development–3rd edition and the Infant‐Toddler Social and Emotional Assessment. Delay was defined as −1 standard deviation relative to the mean of controls. The estimand of interest was the mean difference/odds ratio (OR) between the EP/ELBW and control groups estimated using linear/logistic regression, adjusted for multiple pregnancy and social risk. A total of 205 EP/ELBW and 201 controls were assessed at 2 years. Delay/concerns were more common in the EP/ELBW group compared with controls, for cognitive (OR 3.7 [95% confidence interval 2.3, 6.0]), language (5.3 [3.1, 9.0]) and motor (3.9 [2.3, 6.3]) development, and social‐emotional competence (4.1 [1.6, 10.2]). Being born EP/ELBW has an adverse effect on cognitive, language and motor development, and social‐emotional competence at 2 years’ corrected age. Close developmental surveillance, including social‐emotional development, is recommended.
Publisher: Wiley
Date: 18-04-2022
DOI: 10.1111/PPE.12879
Abstract: Although outcomes for infants born extremely low birthweight (ELBW g birthweight) have improved over time, it is important to document survival and morbidity changes following the advent of modern neonatal intensive care in the 1990s. To describe trends in survival, perinatal outcomes and neurodevelopment to 2 years’ corrected age over time across six discrete geographic cohorts born ELBW between 1979 and 2017. Analysis of data from discrete population‐based prospective cohort studies of all live births free of lethal anomalies with birthweight 500–999 g in the state of Victoria, Australia, over 6 eras: 1979–80, 1985–87, 1991–92, 1997, 2005 and 2016–17. Perinatal data collected included survival, duration and type of respiratory support, neonatal morbidities and two‐year neurodevelopmental outcomes. More ELBW live births were inborn (born in a maternity hospital with a neonatal intensive care unit) over time (1979–80, 70% 2016–17, 84%), and more were offered active care (1979–80, 58% 2016–17, 90%). Survival to 2 years rose substantially, from 25% in 1979–80 to 80% in 2016–17. In survivors, rates of any assisted ventilation rose from 75% in 1979–80 to 99% in 2016–17. Cystic periventricular leukomalacia, severe retinopathy of prematurity and blindness improved across eras. Two‐year data were available for 95% (1054/1109) of survivors. Rates of cerebral palsy, deafness and major neurodevelopmental disability changed little over time. The annual numbers with major neurodevelopmental disability increased from 12.5 in 1979–80 to 30 in 2016–17, but annual numbers free of major disability increased much more, from 31 in 1979–80 to 147 in 2016–17. Active care and survival rates in ELBW children have increased dramatically since 1979 without large changes in neonatal morbidities. The numbers of survivors free of major neurodevelopmental disability have increased more over time than those with major disability.
Publisher: Springer Science and Business Media LLC
Date: 30-06-2018
DOI: 10.1007/S11682-018-9918-9
Abstract: 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.
No related grants have been discovered for Elisha Josev.