Obstetrics and Gynaecology - Research Publications

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    Trends in survival, perinatal morbidities and two-year neurodevelopmental outcomes in extremely low-birthweight infants over four decades
    Zayegh, AM ; Doyle, LW ; Boland, RA ; Mainzer, R ; Spittle, AJ ; Roberts, G ; Hickey, LM ; Anderson, PJ ; Cheong, JLY (WILEY, 2022-09)
    BACKGROUND: Although outcomes for infants born extremely low birthweight (ELBW; <1000 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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    School Readiness in Children Born <30 Weeks' Gestation at Risk for Developmental Coordination Disorder: A Prospective Cohort Study
    Spittle, AJ ; Olsen, JE ; FitzGerald, TL ; Cameron, KL ; Albesher, RA ; Mentiplay, BF ; Treyvaud, K ; Burnett, A ; Lee, KJ ; Pascoe, L ; Roberts, G ; Doyle, LW ; Anderson, P ; Cheong, JLY (LIPPINCOTT WILLIAMS & WILKINS, 2022-06)
    OBJECTIVE: The objective of this study was to determine whether school readiness differs between children born <30 weeks' gestation who are classified as at risk for developmental coordination disorder (DCD) and those who are not. METHODS: This study was a prospective cohort study of children born <30 weeks' gestation. Children were classified as at risk for DCD at a corrected age of 4 to 5 years if they scored <16th centile on the Movement Assessment Battery for Children-Second Edition (MABC-2), had a full scale IQ score of ≥80 on the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV), and had no cerebral palsy. Children were assessed on 4 school readiness domains: (1) health/physical development [Physical Health domain of Pediatric Quality of Life Inventory (PedsQL), Pediatric Evaluation of Disability Inventory Computer Adaptive Test, and Little Developmental Coordination Disorder Questionnaire], (2) social-emotional development (Strengths and Difficulties Questionnaire and PedsQL psychosocial domains), (3) cognitive skills/general knowledge (WPPSI-IV), and (4) language skills (WPPSI-IV). RESULTS: Of 123 children assessed, 16 were ineligible (IQ < 80 or cerebral palsy: n = 15; incomplete MABC-2: n = 1); 28 of 107 (26%) eligible children were at risk for DCD. Children at risk for DCD had poorer performance on all school readiness domains, with group differences of more than 0.4 SD in health/physical development, social-emotional development, and language skills and up to 0.8 SD for cognitive skills/general knowledge compared with those not at risk of DCD. CONCLUSION: Being at risk for DCD in children born <30 weeks' gestation is associated with challenges in multiple school readiness domains, not only the health/physical domain.
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    Thirteen-Year Outcomes of a Randomized Clinical Trial of Early Preventive Care for Very Preterm Infants and Their Parents
    Stedall, PM ; Spencer-Smith, MM ; Mainzer, RM ; Treyvaud, K ; Burnett, AC ; Doyle, LW ; Spittle, AJ ; Anderson, PJ (MOSBY-ELSEVIER, 2022-07)
    OBJECTIVE: To evaluate 13-year outcomes of a randomized controlled trial of preventive care (VIBeS Plus) for infants born very preterm and their parents and examine whether possible effects of intervention varied by family social risk. STUDY DESIGN: Families were randomized to an intervention arm (n = 61) or a standard care arm (n = 59). The intervention was delivered at home by psychologists and physiotherapists over the infants' first year, focusing on infant development and parental mental health. At 13 years corrected age, cognitive, motor, and behavioral outcomes, and parental mental health were assessed. Primary estimands were between-group mean differences, estimated using multiple imputed regression models. RESULTS: Follow-up included 81 surviving children (69%). There was little evidence of benefits of the intervention for IQ, attention, executive functioning, working memory, and academic skills regardless of level of social risk. Specifically, mean differences in adolescent cognitive outcomes ranged from -2.0 units (95% CI, -9.9 to 5.9) in favor of standard treatment to 5.1 units (95% CI, -2.3 to 12.5) favoring the intervention. A group-by-social risk interaction was observed only for adolescent motor outcomes, with mean differences favoring the intervention for those at higher social risk (balance, 4.9; 95% CI, 1.3-8.5; total motor, 3.2; 95% CI, 0.3-6.2), but not those at lower social risk (balance, -0.3; 95% CI, -2.4 to 1.9; total motor, 0.03; 95% CI, -1.9 to 2.0). Mean differences in adolescent behavior and parental mental health ranged from -6.6 (95% CI -13.8, 0.5) to -0.2 (95% CI, -1.9 to 1.4) and -1.8 (95% CI, -4.1 to 0.6) to -1.7 (95% CI, -4.3 to 1.0), respectively, indicating a pattern of fewer symptoms in the intervention group. CONCLUSIONS: Benefits of the intervention persisted for adolescent behavior, with better motor outcomes observed in those from socially disadvantaged families. Replication with larger samples, multiple informant reports, and assessment of quality of life-related outcomes is warranted. TRIAL REGISTRATION: http://www.anzctr.org.au/: ACTRN12605000492651.
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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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    Identifying research priorities in newborn medicine: a Delphi study of parents' views
    Eeles, AL ; Burnett, AC ; Cheong, JLY ; Aldis, A ; Pallot, L ; Polonidis, T ; Rust, K ; Hunt, RW ; Delany, C ; Spittle, AJ (BMJ PUBLISHING GROUP, 2021-11)
    OBJECTIVE: Neonatal conditions can have lifelong implications for the health and well-being of children and families. Traditionally, parents and patients have not been included in shaping the agenda for research and yet they are profoundly affected by the neonatal experience and its consequences. This study aimed to identify consensus research priorities among parents/patients of newborn medicine in Australia and New Zealand. DESIGN: Parents/patients with experience of neonatal care in Australia and New Zealand completed an online Delphi study to identify research priorities across four epochs (neonatal admission, early childhood, childhood/adolescence and adulthood). Parents/patients first generated key challenges in each of these epochs. Through inductive thematic analysis, recurring topics were identified and research questions generated. Parents/patients rated these questions in terms of priorities and a list of questions consistently rated as high priority was identified. PARTICIPANTS: 393 individuals participated, 388 parents whose children had received neonatal care and 5 adults who had received neonatal care themselves. RESULTS: Many research questions were identified as high-priority across the lifespan. These included how to best support parental mental health, relationships between parents and neonatal clinical staff (including involvement in care and communication), bonding and the parent-child relationship, improving neonatal medical care and addressing long-term impacts on child health and neurodevelopment. CONCLUSIONS: Parents with experience of newborn medicine have strong, clear and recurring research priorities spanning neonatal care practices, psychological and other impacts on families, and impacts on child development. These findings should guide neonatal research efforts. In addition to generating new knowledge, improved translation of existing evidence to parents is also needed.
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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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    Development of brain white matter and math computation ability in children born very preterm and full-term
    Collins, SE ; Thompson, DK ; Kelly, CE ; Yang, JYM ; Pascoe, L ; Inder, TE ; Doyle, LW ; Cheong, JLY ; Burnett, AC ; Anderson, PJ (ELSEVIER SCI LTD, 2021-10)
    Children born very preterm (VPT; <32 weeks' gestation) have alterations in brain white matter and poorer math ability than full-term (FT) peers. Diffusion-weighted magnetic resonance imaging studies suggest a link between white matter microstructure and math in VPT and FT children, although longitudinal studies using advanced modelling are lacking. In a prospective longitudinal cohort of VPT and FT children we used Fixel-Based Analysis to investigate associations between maturation of white matter fibre density (FD), fibre-bundle cross-section (FC), and combined fibre density and cross-section (FDC) and math computation ability at 7 (n = 136 VPT; n = 32 FT) and 13 (n = 130 VPT; n = 44 FT) years, as well as between change in white matter and math computation ability from 7 to 13 years (n = 103 VPT; n = 21 FT). In both VPT and FT children, higher FD, FC and FDC in visual, sensorimotor and cortico-thalamic/thalamo-cortical white matter tracts were associated with better math computation ability at 7 and 13 years. Longitudinally, accelerated maturation of the posterior body of the corpus callosum (FDC) was associated with greater math computation development. White matter-math associations were similar for VPT and FT children. In conclusion, white matter maturation is associated with math computation ability across late childhood, irrespective of birth group.
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    Individual Attention Patterns in Children Born Very Preterm and Full Term at 7 and 13 Years of Age
    Bogicevic, L ; Pascoe, L ; Nguyen, T-N-N ; Burnett, AC ; Verhoeven, M ; Thompson, DK ; Cheong, JLY ; Inder, TE ; van Baar, AL ; Doyle, LW ; Anderson, PJ (CAMBRIDGE UNIV PRESS, 2021-11)
    OBJECTIVE: To identify attention profiles at 7 and 13 years, and transitions in attention profiles over time in children born very preterm (VP; <30 weeks' gestation) and full term (FT), and examine predictors of attention profiles and transitions. METHODS: Participants were 167 VP and 60 FT children, evaluated on profiles across five attention domains (selective, shifting and divided attention, processing speed, and behavioral attention) at 7 and 13 years using latent profile analyses. Transitions in profiles were assessed with contingency tables. For VP children, biological and social risk factors were tested as predictors with a multinomial logistic regression. RESULTS: At 7 and 13 years, three distinct profiles of attentional functioning were identified. VP children were 2-3 times more likely to show poorer attention profiles compared with FT children. Transition patterns between 7 and 13 years were stable average, stable low, improving, and declining attention. VP children were two times less likely to have a stable average attention pattern and three times more likely to have stable low or improving attention patterns compared with FT children. Groups did not differ in declining attention patterns. For VP children, brain abnormalities on neonatal MRI and greater social risk at 7 years predicted stable low or changing attention patterns over time. CONCLUSIONS: VP children show greater variability in attention profiles and transition patterns than FT children, with almost half of the VP children showing adverse attention patterns over time. Early brain pathology and social environment are markers for attentional functioning.
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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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    Missing out on precious time: Extending paid parental leave for parents of babies admitted to neonatal intensive or special care units for prolonged periods
    Spittle, AJ ; McKinnon, C ; Huang, L ; Burnett, A ; Cameron, K ; Doyle, LW ; Anderson, P ; Baird, M ; Colditz, P ; Cruz, M ; Pussell, K ; Dalziel, K ; Eeles, A ; Newnham, J ; Hunt, RW ; Cheong, J (WILEY, 2022-03)
    In Australia, approximately 18% of newborn babies are admitted to a neonatal intensive or special care nursery. While most babies admitted to a neonatal intensive or special care nursery are discharged home within a few weeks, around 6% of babies spend more than 2 weeks in hospital. For the parents of these babies, much of their leave entitlements (Australian Government Paid Parental Leave Scheme is up to18 weeks for the primary care giver and up to 2 weeks for partners) are used before their baby comes home from hospital. The time babies and parents spend together in the early developmental period, during the hospitalisation and when the baby is discharged home, is crucial for optimal child development and bonding. Yet care givers who have a baby admitted to neonatal intensive or special care for extended periods are not currently entitled to any extra parental leave payments in Australia. We recommend the Australian Paid Parental Leave Act is changed to allow primary carers access to 1 week of extra parental leave pay for every week in hospital (for babies admitted to hospital for more than 2 weeks), up to a maximum of 14 weeks. For fathers and partners of these babies, we recommend an additional 2 weeks of extra Dad and Partner Pay. The net cost, taking into account likely productivity benefits, would be less than 1.5% of the current cost of the scheme and would improve health and socio-economic outcomes for the baby, family and society.