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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    Early motor repertoire and neurodevelopment at 2 years in infants born extremely preterm or extremely-low-birthweight
    Kwong, AKL ; Doyle, LW ; Olsen, JE ; Eeles, AL ; Lee, KJ ; Cheong, JLY ; Spittle, AJ (WILEY, 2022-07)
    AIM: To determine the relationship between early motor repertoire and 2-year neurodevelopment in infants born extremely preterm (<28 weeks' gestation) or extremely-low-birthweight (ELBW) (<1000g). METHOD: This was a geographical prospective cohort of 139 infants born extremely preterm/ELBW (mean gestational age 26.7 weeks, standard deviation [SD] 2.0, 68/139 [49%] male), with parent-recorded videos suitable for scoring the General Movements Assessment (GMA). Motor repertoire was assessed using the Motor Optimality Score-Revised (MOS-R), with and without the fidgety movement subsection, and the GMA alone at 12 to 13+6  weeks corrected age and 14 to 15+6  weeks corrected age. At 2 years corrected age, impaired development was defined as Bayley Scales of Infant and Toddler Development, Third Edition motor and cognitive development scores 1SD or less relative to controls born at term; paediatricians diagnosed cerebral palsy (CP). RESULTS: Greater MOS-R scores at 14 to 15+6  weeks corrected age were associated with lower odds of CP (odds ratio [OR] per 1-point increase=0.83, 95% confidence interval [CI]=0.71-0.99), and motor (OR=0.93, 95% CI=0.87-0.99), or cognitive impairment (OR=0.94, 95% CI=0.88-0.99). Absent/abnormal GMA at 14 to 15+6 weeks was associated with CP and motor delay. There was little evidence that MOS-R scores at 12 to 13+6 weeks were associated with neurodevelopmental outcomes at 2 years. INTERPRETATION: Poorer MOS-R scores and absent/abnormal GMA, scored from parent-recorded videos at 14 to 15+6  weeks gestational age, are associated with CP and developmental impairment in 2-year-old infants born extremely preterm/ELBW.
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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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    Effect of Treatment of Clinical Seizures vs Electrographic Seizures in Full-Term and Near-Term Neonates A Randomized Clinical Trial
    Hunt, RW ; Liley, HG ; Wagh, D ; Schembri, R ; Lee, KJ ; Shearman, AD ; Francis-Pester, S ; DeWaal, K ; Cheong, JYL ; Olischar, M ; Badawi, N ; Wong, FY ; Osborn, DA ; Rajadurai, VS ; Dargaville, PA ; Headley, B ; Wright, I ; Colditz, PB (AMER MEDICAL ASSOC, 2021-12-17)
    IMPORTANCE: Seizures in the neonatal period are associated with increased mortality and morbidity. Bedside amplitude-integrated electroencephalography (aEEG) has facilitated the detection of electrographic seizures; however, whether these seizures should be treated remains uncertain. OBJECTIVE: To determine if the active management of electrographic and clinical seizures in encephalopathic term or near-term neonates improves survival free of severe disability at 2 years of age compared with only treating clinically detected seizures. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted in tertiary newborn intensive care units recruited from 2012 to 2016 and followed up until 2 years of age. Participants included neonates with encephalopathy at 35 weeks' gestation or more and younger than 48 hours old. Data analysis was completed in April 2021. INTERVENTIONS: Randomization was to an electrographic seizure group (ESG) in which seizures detected on aEEG were treated in addition to clinical seizures or a clinical seizure group (CSG) in which only seizures detected clinically were treated. MAIN OUTCOMES AND MEASURES: Primary outcome was death or severe disability at 2 years, defined as scores in any developmental domain more than 2 SD below the Australian mean assessed with Bayley Scales of Neonate and Toddler Development, 3rd ed (BSID-III), or the presence of cerebral palsy, blindness, or deafness. Secondary outcomes included magnetic resonance imaging brain injury score at 5 to 14 days, time to full suck feeds, and individual domain scores on BSID-III at 2 years. RESULTS: Of 212 randomized neonates, the mean (SD) gestational age was 39.2 (1.7) weeks and 122 (58%) were male; 152 (72%) had moderate to severe hypoxic-ischemic encephalopathy (HIE) and 147 (84%) had electrographic seizures. A total of 86 neonates were included in the ESG group and 86 were included in the CSG group. Ten of 86 (9%) neonates in the ESG and 4 of 86 (4%) in the CSG died before the 2-year assessment. The odds of the primary outcome were not significantly different in the ESG group compared with the CSG group (ESG, 38 of 86 [44%] vs CSG, 27 of 86 [31%]; odds ratio [OR], 1.83; 95% CI, 0.96 to 3.49; P = .14). There was also no significant difference in those with HIE (OR, 1.77; 95% CI, 0.84 to 3.73; P = .26). There was evidence that cognitive outcomes were worse in the ESG (mean [SD] scores, ESG: 97.4 [17.7] vs CSG: 103.8 [17.3]; mean difference, -6.5 [95% CI, -1.2 to -11.8]; P = .01). There was little evidence of a difference in secondary outcomes, including time to suck feeds, seizure burden, or brain injury score. CONCLUSIONS AND RELEVANCE: Treating electrographic and clinical seizures with currently used anticonvulsants did not significantly reduce the rate of death or disability at 2 years in a heterogeneous group of neonates with seizures. TRIAL REGISTRATION: http://anzctr.org.au Identifier: ACTRN12611000327987.
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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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    Barriers and facilitators to community participation for preschool age children born very preterm: a prospective cohort study
    Cameron, KL ; FitzGerald, TL ; Albesher, RA ; McGinley, JL ; Allison, K ; Lee, KJ ; Cheong, JLY ; Spittle, AJ (WILEY, 2021-06)
    AIM: We compared preschool age children born very preterm with term-born controls to: (1) understand the association between very preterm birth and community participation, (2) determine if motor impairment or social risk affect participation differently between groups, and (3) understand environmental barriers and supports to participation for parents. METHOD: Forty-eight children born very preterm (<30wks' gestation; 22 males, 26 females) and 96 controls (47 males, 49 females) were assessed at 4 to 5 years' corrected age for community participation using the Young Children's Participation and Environment Measure. Motor skills were assessed using the Movement Assessment Battery for Children, Second Edition and the Little Developmental Coordination Disorder Questionnaire. RESULTS: Children born very preterm participated less frequently than term-born children (difference in means=-0.28, 95% confidence interval [CI] -0.54 to -0.03, p=0.029). Social risk was associated with lower frequency (interaction p<0.001) and involvement (interaction p=0.05) in community activities for children in the very preterm group only. Parents of children born very preterm perceived more barriers (odds ratio=4.32, 95% CI 1.46-12.77, p=0.008) and environmental factors to be less supportive of participation than parents of controls (difference in medians=-6.21, 95% CI -11.42 to -1.00, p=0.02). INTERPRETATION: Children born very preterm may benefit from ongoing support to promote participation, especially in families of higher social risk.
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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.