Obstetrics and Gynaecology - Research Publications

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    Investigating the brain structural connectome following working memory training in children born extremely preterm or extremely low birth weight
    Kelly, CE ; Harding, R ; Lee, KJ ; Pascoe, L ; Josev, EK ; Spencer-Smith, MM ; Adamson, C ; Beare, R ; Nosarti, C ; Roberts, G ; Doyle, LW ; Seal, ML ; Thompson, DK ; Anderson, PJ (WILEY, 2021-10)
    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.
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    Translating antenatal magnesium sulphate neuroprotection for infants born <28 weeks' gestation into practice: A geographical cohort study
    Doyle, LW ; Spittle, AJ ; Olsen, JE ; Kwong, A ; Boland, RA ; Lee, KJ ; Anderson, PJ ; Cheong, JLY (WILEY, 2021-08)
    BACKGROUND: 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 <28 weeks' gestation. MATERIALS AND METHODS: Participants comprised all survivors born <28 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. RESULTS: 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). CONCLUSIONS: Antenatal magnesium sulphate is being translated into clinical practice for infants born <28 weeks' gestation, but there is room for improvement. It is associated with lower rates of cerebral palsy in survivors.
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    Psychiatric disorders in individuals born very preterm / very low-birth weight: An individual participant data (IPD) meta-analysis
    Anderson, PJ ; de Miranda, DM ; Albuquerque, MR ; Indredavik, MS ; Evensen, KA ; Van Lieshout, R ; Saigal, S ; Taylor, HG ; Raikkonen, K ; Kajantie, E ; Marlow, N ; Johnson, S ; Woodward, LJ ; Austin, N ; Nosarti, C ; Jaekel, J ; Wolke, D ; Cheong, JL ; Burnett, A ; Treyvaud, K ; Lee, KJ ; Doyle, LW (ELSEVIER, 2021-12)
    BACKGROUND: Data on psychiatric disorders in survivors born very preterm (VP; <32 weeks) or very low birthweight (VLBW; <1500 g) are sparse. We compared rates of psychiatric diagnoses between VP/VLBW and term-born, normal birthweight (term/NBW) control participants. METHODS: This individual participant data (IPD) meta-analysis pooled data from eligible groups in the Adults born Preterm International Collaboration (APIC). Inclusion criteria included: 1) VP/VLBW group (birth weight <1500 g and/or gestational age <32 weeks), 2) normal birth weight/term-born control group (birth weight >2499 g and/or gestational age ≥37 weeks), and 3) structured measure of psychiatric diagnoses using DSM or ICD criteria. Diagnoses of interest were Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Anxiety Disorder, Mood Disorder, Disruptive Behaviour Disorder (DBD), Eating Disorder, and Psychotic Disorder. A systematic search for eligible studies was conducted (PROSPERO Registration Number 47555). FINDINGS: Data were obtained from 10 studies (1385 VP/VLBW participants, 1780 controls), using a range of instruments and approaches to assigning diagnoses. Those born VP/VLBW had ten times higher odds of meeting criteria for ASD (odds ratio [OR] 10·6, 95% confidence interval [CI] 2·50, 44·7), five times higher odds of meeting criteria for ADHD (OR 5·42, 95% CI 3·10, 9·46), twice the odds of meeting criteria for Anxiety Disorder (OR 1·91, 95% CI 1·36, 2·69), and 1·5 times the odds of meeting criteria for Mood Disorder (OR 1·51, 95% CI 1·08, 2·12) than controls. This pattern of findings was consistent within age (<18 years vs. ≥18 years) and sex subgroups. INTERPRETATION: Our data suggests that individuals born VP/VLBW might have higher odds of meeting criteria for certain psychiatric disorders through childhood and into adulthood than term/NBW controls. Further research is needed to corroborate our results and identify factors associated with psychiatric disorders in individuals born VP/VLBW. FUNDING: Australia's National Health & Medical Research Council; CAPES (Coordenação de Aperfeiçoamento de Pessoal deNível Superior) - International Cooperation General Program; Canadian Institutes of Health Research Team Grant; National Council for Scientific and Technological Development (CNPq); Academy of Finland; Sigrid Juselius Foundation; Signe and Ane Gyllenberg Foundation; European Union's Horizon 2020 research and innovation programme: Project RECAP-Preterm; European Commission Dynamics of Inequality Across the Life-course: structures and processes (DIAL); Neurologic Foundation of New Zealand; MRC programme grant; Health Research Council of New Zealand; National Institutes of Health, USA; The Research Council of Norway; Joint Research Committee between St. Olavs Hospital and Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU); Liaison Committee between Central Norway Regional Health Authority and NTNU.
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    Impact of moderate and late preterm birth on neurodevelopment, brain development and respiratory health at school age: protocol for a longitudinal cohort study (LaPrem study)
    Cheong, J ; Cameron, KLI ; Thompson, D ; Anderson, PJ ; Ranganathan, S ; Clark, R ; Mentiplay, B ; Burnett, A ; Lee, K ; Doyle, LW ; Spittle, AJ (BMJ PUBLISHING GROUP, 2021)
    INTRODUCTION: Children born moderate to late preterm (MLP, 32-36 weeks' gestation) account for approximately 85% of all preterm births globally. Compared with children born at term, children born MLP are at increased risk of poor neurodevelopmental outcomes. Despite making up the largest group of preterm children, developmental outcomes of children born MLP are less well studied than in other preterm groups. This study aimed to (1) compare neurodevelopmental, respiratory health and brain magnetic resonance imaging (MRI) outcomes between children born MLP and term at 9 years of age; (2) examine the differences in brain growth trajectory from infancy to 9 years between children born MLP and term; and in children born MLP; (3) examine the relationship between brain development and neurodevelopment at 9 years; and (4) identify risk factors for poorer outcomes at 9 years. METHODS AND ANALYSIS: The "LaPrem" (Late Preterm MRI Study) study is a longitudinal cohort study of children born MLP and term controls, born at the Royal Women's Hospital in Melbourne, Australia, between 2010 and 2013. Participants were recruited in the neonatal period and were previously followed up at 2 and 5 years. This 9-year school-age follow-up includes neuropsychology, motor and physical activities, and lung function assessments, as well as brain MRI. Outcomes at 9 years will be compared between birth groups using linear and logistic regressions. Trajectories of brain development will be compared between birth groups using mixed effects models. The relationships between MRI and neurodevelopmental outcomes, as well as other early predictors of poor 9-year outcomes, will be explored using linear and logistic regression. ETHICS AND DISSEMINATION: This study was approved by the human research ethics committee at the Royal Children's Hospital, Melbourne, Australia. Study outcomes will be disseminated through peer-reviewed publications, conference presentations and social media.
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    Changing consumption of resources for respiratory support and short-term outcomes in four consecutive geographical cohorts of infants born extremely preterm over 25 years since the early 1990s
    Cheong, JLY ; Olsen, JE ; Huang, L ; Dalziel, KM ; Boland, RA ; Burnett, AC ; Haikerwal, A ; Spittle, AJ ; Opie, G ; Stewart, AE ; Hickey, LM ; Anderson, PJ ; Doyle, LW (BMJ PUBLISHING GROUP, 2020)
    OBJECTIVES: 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. DESIGN: Prospective longitudinal cohort study. SETTING: The State of Victoria, Australia. PARTICIPANTS: 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). OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.
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    Working memory training and brain structure and function in extremely preterm or extremely low birth weight children
    Kelly, CE ; Thompson, DK ; Chen, J ; Josev, EK ; Pascoe, L ; Spencer-Smith, MM ; Adamson, C ; Nosarti, C ; Gathercole, S ; Roberts, G ; Lee, KJ ; Doyle, LW ; Seal, ML ; Anderson, PJ (WILEY, 2020-02-15)
    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.
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    Tracking regional brain growth up to age 13 in children born term and very preterm
    Thompson, DK ; Matthews, LG ; Alexander, B ; Lee, KJ ; Kelly, CE ; Adamson, CL ; Hunt, RW ; Cheong, JLY ; Spencer-Smith, M ; Neil, JJ ; Seal, ML ; Inder, TE ; Doyle, LW ; Anderson, PJ (NATURE PUBLISHING GROUP, 2020-02-04)
    Serial regional brain growth from the newborn period to adolescence has not been described. Here, we measured regional brain growth in 216 very preterm (VP) and 45 full-term (FT) children. Brain MRI was performed at term-equivalent age, 7 and 13 years in 82 regions. Brain volumes increased between term-equivalent and 7 years, with faster growth in the FT than VP group. Perinatal brain abnormality was associated with less increase in brain volume between term-equivalent and 7 years in the VP group. Between 7 and 13 years, volumes were relatively stable, with some subcortical and cortical regions increasing while others reduced. Notably, VP infants continued to lag, with overall brain size generally less than that of FT peers at 13 years. Parieto-frontal growth, mainly between 7 and 13 years in FT children, was associated with higher intelligence at 13 years. This study improves understanding of typical and atypical regional brain growth.