Obstetrics and Gynaecology - Research Publications

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    Relationships between early postnatal cranial ultrasonography linear measures and neurodevelopment at 2 years in infants born at <30 weeks' gestational age without major brain injury
    Cuzzilla, R ; Cowan, FM ; Rogerson, S ; Anderson, PJ ; Doyle, LW ; Cheong, JLY ; Spittle, A (BMJ PUBLISHING GROUP, 2023-09)
    OBJECTIVE: To explore relationships of early postnatal cranial ultrasonography (cUS) linear measures of brain size and brain growth with neurodevelopment at 2 years in infants born <30 weeks' gestational age (GA) and free of major brain injury. DESIGN: Prospective observational cohort study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: 139 infants born <30 weeks' GA, free of major brain injury on neonatal cUS and without congenital or chromosomal anomalies known to affect neurodevelopment. INTERVENTION: Linear measures of brain tissue and fluid spaces made from cUS at 1-week, 1-month and 2-months' postnatal age. MAIN OUTCOME MEASURES: Cognitive, language and motor scores on the Bayley Scales of Infant and Toddler Development, third edition at 2 years' corrected age. RESULTS: 313 scans were evaluated from the 131 children who were assessed at 2 years. Larger measures of the corpus callosum at 1 week, 1 month and 2 months, cerebellum and vermis at 2 months and faster positive growth of the cerebellum and vermis between 1 month and 2 months, were related to higher cognitive and language scores at 2 years. No relation between tissue measures and motor scores was found. Larger measures, and faster rate of increase, of fluid spaces within the first weeks after birth were related to better cognitive, language and motor outcomes at 2 years. CONCLUSIONS: Early postnatal cUS linear measures of brain tissue were related to cognitive and language development at 2 years in infants born <30 weeks' GA without major brain injury. Relationships between cUS linear measures of fluid spaces in the early postnatal period and later neurodevelopment warrant further exploration.
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    Expiratory airflow at 7-8 years of age in children born extremely low birthweight from 14 years before to 14 years after the introduction of exogenous surfactant
    Doyle, LW ; Ranganathan, S ; Spittle, AJ ; Opie, G ; Mainzer, RM ; Cheong, JLY (ELSEVIER, 2023-08)
    BACKGROUND: It is unclear if expiratory airflow in survivors born extremely low birth weight (ELBW; 500-999 g) has improved after the introduction of exogenous surfactant into clinical practice in 1991. The primary aim of this study was to describe the changes in airflow at 7-8 years of age of survivors born ELBW in five discrete cohorts from 14 years before to 14 years after the introduction of exogenous surfactant into clinical practice. METHODS: The cohorts comprised consecutive survivors born ELBW in 1977-82 and 1985-87 at the Royal Women's Hospital, Melbourne, and in 1991-92, 1997 and 2005 in the state of Victoria, Australia. Survival rates to 2-years of age for infants born ELBW in the state of Victoria rose from approximately 1-in-4 to 3-in-4 over the time of this study. Expiratory airflow measurements at 7-8 years included the forced expired volume in 1 s (FEV1), converted to z-scores for age, height, sex, and race. FINDINGS: There were 596 ELBW participants with expiratory flow data, 280 (47%) of whom had bronchopulmonary dysplasia (BPD). Overall, there was little change in zFEV1 over the 28-year period (mean change per year; 0.003, 95% CI -0.010, 0.015, P = 0.67). There was, however, evidence of an interaction between BPD and year; zFEV1 in those who had BPD fell over time (mean change per year -0.019, 95% CI -0.037, -0.009, P = 0.035), whereas zFEV1 improved in those who did not have BPD (mean change per year 0.021, 95% CI 0.006, 0.037, P = 0.007). INTERPRETATION: Contrary to recent evidence, expiratory airflow of children born ELBW has not improved with the introduction of surfactant, and may be deteriorating in those who had BPD. FUNDING: National Health and Medical Research Council (Australia); Victorian Government's Operational Infrastructure Support Program.
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    Parent-recorded videos of infant spontaneous movement: Comparisons at 3-4 months and relationships with 2-year developmental outcomes in extremely preterm, extremely low birthweight and term-born infants
    Kwong, AKL ; Doyle, LW ; Olsen, JE ; Eeles, AL ; Zannino, D ; Mainzer, RM ; Cheong, JLY ; Spittle, AJ (WILEY, 2022-09)
    BACKGROUND: Infants born extremely preterm (EP, <28-week gestational age) or extremely low birthweight (ELBW, <1000 g) are at risk of developmental delay and cerebral palsy (CP). The General Movements Assessment (GMA) and its extension, the Motor Optimality Score, revised (MOS-R) (assesses movement patterns and posture), may help to identify early delays. OBJECTIVES: To compare differences in the MOS-R scored from parent-recorded videos between infants born EP/ELBW and term-born infants, to determine relationships between the MOS-R and 2-year cognitive, language and motor outcomes and if any relationships differ between birth groups and the association of the GMA (fidgety) with CP. METHODS: A geographical cohort (EP/ELBW and term-control infants) was assessed using the MOS-R inclusive of the GMA at 3- to 4-month corrected age (CA), and the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III) at 2-year CA. Differences in mean total MOS-R between groups, relationships between MOS-R and 2-year outcomes and relationships between GMA (fidgety) and CP in infants born EP/ELBW were estimated using linear/logistic regression. RESULTS: Three hundred and twelve infants (147 EP/ELBW; 165 term) had complete MOS-R and Bayley-III assessments. Mean MOS-R was lower in infants born EP/ELBW than controls (mean difference -3.2, 95% confidence interval [CI] -4.2, -2.3). MOS-R was positively related to cognitive (β [regression coefficient] = 0.71, 95% CI 0.27, 1.15), language (β = 0.96, 95% CI 0.38, 1.54) and motor outcomes (β = .89, 95% CI 0.45, 1.34). There was little evidence for interaction effects between birth groups for any outcome. Absent/abnormal fidgety movements were related to CP in children born EP/ELBW (risk ratio 5.91, 95% CI 1.48, 23.7). CONCLUSIONS: Infants born EP/ELBW have lower MOS-R than infants born at term. A higher MOS-R is related to better outcomes for 2-year development, with similar relationships in both birth groups. Absent/abnormal fidgety movements are related to CP in EP/ELBW survivors.
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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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    Postnatal corticosteroids and developmental outcomes in extremely preterm or extremely low birth weight infants: The Victorian Infant Collaborative Study 2016-17 cohort
    Douglas, E ; Hodgson, KA ; Olsen, JE ; Manley, BJ ; Roberts, CT ; Josev, E ; Anderson, PJ ; Doyle, LW ; Davis, PG ; Cheong, JLY (WILEY, 2023-06)
    AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
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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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    Growth from infancy to adulthood and associations with cardiometabolic health in individuals born extremely preterm
    Cheong, JLY ; Olsen, JE ; Konstan, T ; Mainzer, RM ; Hickey, LM ; Spittle, AJ ; Wark, JD ; Cheung, MM ; Garland, SM ; Duff, J ; Clark, M ; Stevens, P ; Doyle, LW (ELSEVIER, 2023-05)
    BACKGROUND: Few studies have tracked growth in children born extremely preterm (EP, <28 weeks' gestation) beyond late adolescence. The relationships between growth parameters (including weight and BMI) through childhood and adolescence with later cardiometabolic health, are unclear in those born EP. We aimed to (i) compare growth from 2 to 25 years between EP and controls; and in the EP group (ii) determine the associations of growth parameters with cardiometabolic health. METHODS: Prospective state-wide cohort of all EP livebirths in Victoria, Australia, in 1991-1992 and contemporaneous term-born controls. Z-scores for weight (z-weight), height (z-height) and BMI (z-BMI) at 2, 5, 8, 18 and 25 years, and cardiometabolic health at 25 years (body composition, glucose tolerance, lipid profiles, blood pressure, exercise capacity) were measured. Growth trajectories were compared between groups using mixed models. The relationships between z-BMI changes/year, and being overweight at different ages, with cardiometabolic health were explored using linear regression. FINDINGS: Z-weight and z-BMI were lower in EP than controls, but the gap decreased with age due to a more rapid rate of rise in z-weight and a decrease in z-height in the EP group compared with controls. Greater increases in z-BMI/year in the EP group were associated with poorer cardiometabolic health [coefficient (95% CI) per 0.1 z-BMI increase/year: visceral fat volume (cm3) 217.8 (160.9, 274.7), triglycerides (mmol/L) 0.45 (0.20, 0.71), systolic blood pressure (mmHg) 8.9 (5.8, 12.0), and exercise capacity (BEEP test maximum level -1.2 (-1.7, -0.7)), all p < 0.001]. The association between being overweight with poorer cardiometabolic health strengthened with age. INTERPRETATION: The catch-up in weight and BMI by young adulthood in survivors born EP may not be desirable as it is associated with poorer cardiometabolic health. The associations of being overweight from mid-childhood with poorer cardiometabolic health may provide a window for intervention. FUNDING: National Health and Medical Research Council of Australia.
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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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    Spatiotemporal gait variables and step-to-step variability in preschool-aged children born < 30 weeks' gestation and at term in preferred speed, dual-task paradigm, and tandem walking
    Albesher, RA ; Spittle, AJ ; Dobson, FL ; Mentiplay, BF ; FitzGerald, TL ; Cameron, KL ; Zannino, D ; Josev, EK ; Doyle, LW ; Cheong, JLY ; McGinley, JL (ELSEVIER IRELAND LTD, 2022-02)
    BACKGROUND: 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. RESEARCH QUESTION: How does the gait pattern of preschool-age children born < 30 weeks compare with term-born controls under a variety of walking conditions? METHODS: 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. RESULTS: 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). SIGNIFICANCE: 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.