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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    Parenting and Neurobehavioral Outcomes in Children Born Moderate-to-Late Preterm and at Term
    McMahon, GE ; Treyvaud, K ; Spencer-Smith, MM ; Spittle, AJ ; Lee, KJ ; Doyle, LW ; Cheong, JL ; Anderson, PJ (MOSBY-ELSEVIER, 2022-02-01)
    Objectives To compare the parenting environment and the relationships between parenting behaviors and concurrent child neurobehavioral outcomes at 2 years of corrected age between children born moderate-to-late preterm (MLP; 32-36 weeks of gestation) and at term (≥37 weeks of gestation). Study design Participants were 129 children born MLP and 110 children born at term and their mothers. Mothers’ parenting behaviors (sensitivity, structuring, nonintrusiveness, nonhostility) were assessed at 2 years of corrected age using the Emotional Availability Scales. Child cognitive and language development were assessed using the Bayley Scales of Infant and Toddler Development, and social–emotional competence using the Infant Toddler Social and Emotional Assessment. Results Mothers of children born MLP and at term displayed similar parenting behaviors overall, with slightly lower nonintrusiveness in mothers of children born MLP (adjusted mean difference −0.32 [–0.60, −0.04]; P = .03). In both groups of children, greater maternal sensitivity was associated with better cognitive development (P < .001 MLP; P = .02 term), increased maternal structuring was associated with better social–emotional competence (P = .02 MLP; P = .03 term), and higher maternal nonintrusiveness was associated with better cognitive, language, and social-emotional outcomes (all P < .04). Greater maternal sensitivity and structuring were associated with better language development in children born MLP but not in children born at term. Conclusions Parenting behaviors are important for neurobehavioral outcomes in children born MLP and at term. Language development may be more strongly influenced by select parenting behaviors in children born MLP compared with children born at term.
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    Relationships between early postnatal cranial ultrasonography linear measures and neurobehaviour at term-equivalent age in infants born <30 weeks' gestational age
    Cuzzilla, R ; Olsen, JE ; Eeles, AL ; Rogerson, SR ; Anderson, PJ ; Cowan, FM ; Doyle, LW ; Cheong, JLY ; Spittle, AJ (ELSEVIER IRELAND LTD, 2022-01)
    BACKGROUND: The relationship between early postnatal brain development and neurobehaviour at term-equivalent age (TEA) remains uncertain. AIM: We aimed to explore relationships between early postnatal cranial ultrasonography (cUS) linear measures of brain size and brain growth with neurobehaviour at TEA in infants born <30 weeks' gestational age (GA). STUDY DESIGN: Prospective observational cohort study. SUBJECTS: 137 infants born <30 weeks' GA without major brain injury on neonatal cUS. OUTCOME MEASURES: Neurobehaviour at TEA assessed using the General Movements Assessment (GMA) and Hammersmith Neonatal Neurological Examination (HNNE). RESULTS: The GMA was administered in 115/137 (84%) infants; 80 (70%) presented with abnormal general movements (GMs) (79 poor repertoire, 1 cramped synchronised). The HNNE was assessed in 106/137 (77%) infants; 52 (49%) had a suboptimal total score. With respect to brain size, larger measures of the corpus callosum length (CCL) and right anterior horn width (AHW) at 1-month were related to lower risk of abnormal GMs, and larger measures of the biparietal diameter at 1-week and 2-months were related to lower risk of a suboptimal HNNE. As for brain growth, increases of the CCL and transcerebellar diameter between birth and 1-month, and left and right AHWs between 1- and 2-months, were related to lower risk of abnormal GMs. CONCLUSION: Early postnatal brain size and brain growth were related to neurobehaviour at TEA in infants born <30 weeks' GA. This study provides preliminary evidence for the prognostic utility of early postnatal cUS linear measures as potential markers of neurodevelopment in later childhood.
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    Brain tissue microstructural and free-water composition 13 years after very preterm birth
    Kelly, C ; Dhollander, T ; Harding, IH ; Khan, W ; Beare, R ; Cheong, JLY ; Doyle, LW ; Seal, M ; Thompson, DK ; Inder, TE ; Anderson, PJ (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2022-07-01)
    There have been many studies demonstrating children born very preterm exhibit brain white matter microstructural alterations, which have been related to neurodevelopmental difficulties. These prior studies have often been based on diffusion MRI modelling and analysis techniques, which commonly focussed on white matter microstructural properties in children born very preterm. However, there have been relatively fewer studies investigating the free-water content of the white matter, and also the microstructure and free-water content of the cortical grey matter, in children born very preterm. These biophysical properties of the brain change rapidly during fetal and neonatal brain development, and therefore such properties are likely also adversely affected by very preterm birth. In this study, we investigated the relationship of very preterm birth (<30 weeks' gestation) to both white matter and cortical grey matter microstructure and free-water content in childhood using advanced diffusion MRI analyses. A total of 130 very preterm participants and 45 full-term control participants underwent diffusion MRI at age 13 years. Diffusion tissue signal fractions derived by Single-Shell 3-Tissue Constrained Spherical Deconvolution were used to investigate brain tissue microstructural and free-water composition. The tissue microstructural and free-water composition metrics were analysed using a voxel-based analysis and cortical region-of-interest analysis approach. Very preterm 13-year-olds exhibited reduced white matter microstructural density and increased free-water content across widespread regions of the white matter compared with controls. Additionally, very preterm 13-year-olds exhibited reduced microstructural density and increased free-water content in specific temporal, frontal, occipital and cingulate cortical regions. These brain tissue composition alterations were strongly associated with cerebral white matter abnormalities identified in the neonatal period, and concurrent adverse cognitive and motor outcomes in very preterm children. The findings demonstrate brain microstructural and free-water alterations up to thirteen years from neonatal brain abnormalities in very preterm children that relate to adverse neurodevelopmental outcomes.
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    Investigating brain structural maturation in children and adolescents born very preterm using the brain age framework
    Kelly, C ; Ball, G ; Matthews, LG ; Cheong, JL ; Doyle, LW ; Inder, TE ; Thompson, DK ; Anderson, PJ (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2022-02-15)
    Very preterm (VP) birth is associated with an increased risk for later neurodevelopmental and behavioural challenges. Although the neurobiological underpinnings of such challenges continue to be explored, previous studies have reported brain volume and morphology alterations in children and adolescents born VP compared with full-term (FT)-born controls. How these alterations relate to the trajectory of brain maturation, with potential implications for later brain ageing, remains unclear. In this longitudinal study, we investigate the relationship between VP birth and brain development during childhood and adolescence. We construct a normative 'brain age' model to predict age over childhood and adolescence based on measures of brain cortical and subcortical volumes and cortical morphology from structural MRI of a dataset of typically developing children aged 3-21 years (n = 768). Using this model, we examined deviations from normative brain development in a separate dataset of children and adolescents born VP (<30 weeks' gestation) at two timepoints (ages 7 and 13 years) compared with FT-born controls (120 VP and 29 FT children at age 7 years; 140 VP and 47 FT children at age 13 years). Brain age delta (brain-predicted age minus chronological age) was, on average, higher in the VP group at both timepoints compared with controls, however this difference had a small to medium effect size and was not statistically significant. Variance in brain age delta was higher in the VP group compared with controls; this difference was significant at the 13-year timepoint. Within the VP group, there was little evidence of associations between brain age delta and perinatal risk factors or cognitive and motor outcomes. Under the brain age framework, our results may suggest that children and adolescents born VP have similar brain structural developmental trajectories to term-born peers between 7 and 13 years of age.
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    Mathematical performance in childhood and early adult outcomes after very preterm birth: an individual participant data meta-analysis
    Jaekel, J ; Anderson, PJ ; Bartmann, P ; Cheong, JLY ; Doyle, LW ; Hack, M ; Johnson, S ; Marlow, N ; Saigal, S ; Schmidt, L ; Sullivan, MC ; Wolke, D (WILEY, 2022-04)
    AIM: To investigate the strength of the independent associations of mathematics performance in children born very preterm (<32wks' gestation or <1500g birthweight) with attending postsecondary education and their current employment status in young adulthood. METHOD: We harmonized data from six very preterm birth cohorts from five different countries and carried out one-stage individual participant data meta-analyses (n=954, 52% female) using mixed effects logistic regression models. Mathematics scores at 8 to 11 years of age were z-standardized using contemporary cohort-specific controls. Outcomes included any postsecondary education, and employment/education status in young adulthood. All models were adjusted for year of birth, gestational age, sex, maternal education, and IQ in childhood. RESULTS: Higher mathematics performance in childhood was independently associated with having attended any postsecondary education (odds ratio [OR] per SD increase in mathematics z-score: 1.36 [95% confidence interval {CI}: 1.03, 1.79]) but not with current employment/education status (OR 1.14 per SD increase [95% CI: 0.87, 1.48]). INTERPRETATION: Among populations born very preterm, childhood mathematics performance is important for adult educational attainment, but not for employment status.
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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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    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.