Obstetrics and Gynaecology - Research Publications
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ItemThe role of social risk in an early preventative care programme for infants born very preterm: a randomized controlled trial(WILEY, 2018-01)AIM: To examine the differential effects of an early intervention programme for infants born preterm on neurodevelopment and parental mental health according to family social risk. METHOD: One hundred and twenty infants born earlier than 30 weeks' gestation were randomized to early intervention (n=61) or control groups (n=59). Cognitive, language, and motor outcomes were assessed by blinded assessors at 2 years, 4 years, and 8 years, and primary caregivers completed questionnaires on their anxiety and depression. Outcomes at each time point were compared between groups using linear regression with an interaction term for social risk (higher/lower). RESULTS: There was evidence of interactions between intervention group and social risk for cognition at 2 years and 4 years, motor function at 4 years, and language at 8 years, with a greater intervention effect in children from higher social risk environments. In contrast, the impact of early intervention on parental depressive symptoms was greater for parents of lower social risk than for those of higher social risk. INTERPRETATION: Effects of early intervention on outcomes for children born preterm and their caregivers varied according to family social risk. Family social risk should be considered when implementing early intervention programmes for children born preterm and their families. WHAT THIS PAPER ADDS: Intervention is associated with better early cognitive functioning for children in higher social risk families. Positive effects of intervention for the high risk group were not sustained at school-age. Intervention has a greater effect on primary caregiver mental health in the lower social risk group compared with higher social risk.
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ItemPredictive value of the Movement Assessment Battery for Children - Second Edition at 4years, for motor impairment at 8years in children born preterm(WILEY, 2017-05)AIM: To assess the predictive validity at 4 years of the Movement Assessment Battery for Children - Second Edition (MABC-2) for motor impairment at 8 years in children born preterm. We also aimed to determine if sex, cognition, medical, or social risks were associated with motor impairment at 8 years or with a change in MABC-2 score between 4 years and 8 years. METHOD: Ninety-six children born at less than 30 weeks' gestation were assessed with the MABC-2 at 4 years and 8 years of age. Motor impairment was defined as less than or equal to the 5th centile. The Differential Ability Scales - Second Edition (DAS-II) was used to measure General Conceptual Ability (GCA) at 4 years, with a score <90 defined as 'below average'. RESULTS: There was a strong association between the MABC-2 total standard scores at 4 years and 8 years (59% variance explained, regression coefficient=0.80, 95% confidence interval [CI] 0.69-0.91, p<0.001). The MABC-2 at 4 years had high sensitivity (79%) and specificity (93%) for predicting motor impairment at 8 years. Below average cognition and higher medical risk were associated with increased odds of motor impairment at 8 years (odds ratio [OR]=15.3, 95% CI 4.19-55.8, p<0.001, and OR=3.77, 95% CI 1.28-11.1, p=0.016 respectively). Sex and social risk did not appear to be associated with motor impairment at 8 years. There was little evidence that any variables were related to change in MABC-2 score between 4 years and 8 years. INTERPRETATION: The MABC-2 at 4 years is predictive of motor functioning in middle childhood. Below average cognition and higher medical risk may be predictors of motor impairment.
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ItemNeurobehaviour at term-equivalent age and neurodevelopmental outcomes at 2 years in infants born moderate-to-late preterm(WILEY, 2017-02)AIM: To examine the association between newborn neurobehavioural assessments and neurodevelopmental outcomes at 2 years in infants born moderate-to-late preterm (MLPT). METHOD: Two-hundred and one infants born MLPT (born 32-36+6 wks' gestation) were assessed with the Hammersmith Neonatal Neurological Examination (HNNE) and NICU Network Neurobehavioral Scale (NNNS), with suboptimal performance defined as scores lower than the 10th centile. Development was assessed at 2 years corrected age with the Bayley Scales of Infant and Toddler Development 3rd Edition, with delay defined as scores less than 1 standard deviation (SD) below the mean. The relationships between neurobehaviour at term and Bayley-III cognitive, language, and motor scales at 2 years were examined using linear regression. RESULTS: Increased odds for cognitive delay were associated with suboptimal HNNE total scores (odds ratio [OR] 2.66; 95% confidence interval [CI] 1.14-6.23, p=0.020) and suboptimal NNNS excitability (OR 3.01; 95% CI 1.33-6.82, p=0.008) and lethargy (OR 4.05; 95% CI 1.75-9.31, p=0.001) scores. Suboptimal lethargy scores on the NNNS were associated with increased odds of language (OR 5.64; 95% CI 1.33-23.85, p=0.019) and motor delay (OR: 6.86; 95% CI 1.64-28.71, p=0.08). INTERPRETATION: Suboptimal performance on specific aspects of newborn neurobehavioural assessments is associated with neurodevelopmental delay at 2 years in children born MLPT.
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ItemWhite matter microstructure is associated with language in children born very preterm(ELSEVIER SCI LTD, 2018)Very preterm birth is associated with altered white matter microstructure and language difficulties, which may compromise communication, social function and academic achievement, but the relationship between these two factors is unclear. The aim of this study was to explore associations between white matter microstructure and language domains of semantics, grammar and phonological awareness at 7-years of age on a whole-brain level and within the arcuate fasciculus, an important language pathway, in very preterm and term-born children. Language was assessed in 145 very preterm-born (<30 weeks' gestation and/or <1250 g birth weight) and 33 term-born children aged 7 years. Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), axon orientation dispersion and axon density were estimated from diffusion magnetic resonance images also obtained at 7 years. The correlation between diffusion values and language was assessed using Tract-Based Spatial Statistics (TBSS). The arcuate fasciculus was delineated using constrained spherical deconvolution tractography and diffusion parameters from this tract were related to language measures using linear regression. While there was evidence for widespread associations between white matter microstructure and language, there was little evidence of differences in these associations between very preterm and term-born groups. TBSS analyses revealed that higher FA and lower AD, RD, and MD in major fibre tracts, including those subserving language, were associated with better semantic, grammar and phonological awareness performance. Higher axon density in widespread fibre tracts was also associated with better semantic performance. The tractography analyses of the arcuate fasciculus showed some evidence for associations between white matter microstructure and language outcomes. White matter microstructural organisation in widespread fibre tracts, including language-relevant pathways, was associated with language performance in whole-brain and tract-based analyses. The associations were similar for very preterm and term-born groups, despite very preterm children performing more poorly across language domains.
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ItemContribution of Brain Size to IQ and Educational Underperformance in Extremely Preterm Adolescents(PUBLIC LIBRARY SCIENCE, 2013-10-09)OBJECTIVES: Extremely preterm (EP) survivors have smaller brains, lower IQ, and worse educational achievement than their term-born peers. The contribution of smaller brain size to the IQ and educational disadvantages of EP is unknown. This study aimed (i) to compare brain volumes from multiple brain tissues and structures between EP-born (< 28 weeks) and term-born (≥ 37 weeks) control adolescents, (ii) to explore the relationships of brain tissue volumes with IQ and basic educational skills and whether this differed by group, and (iii) to explore how much total brain tissue volume explains the underperformance of EP adolescents compared with controls. METHODS: Longitudinal cohort study of 148 EP and 132 term controls born in Victoria, Australia in 1991-92. At age 18, magnetic resonance imaging-determined brain volumes of multiple tissues and structures were calculated. IQ and educational skills were measured using the Wechsler Abbreviated Scale of Intelligence (WASI) and the Wide Range Achievement Test(WRAT-4), respectively. RESULTS: Brain volumes were smaller in EP adolescents compared with controls (mean difference [95% confidence interval] of -5.9% [-8.0, -3.7%] for total brain tissue volume). The largest relative differences were noted in the thalamus and hippocampus. The EP group had lower IQs(-11.9 [-15.4, -8.5]), spelling(-8.0 [-11.5, -4.6]), math computation(-10.3 [-13.7, -6.9]) and word reading(-5.6 [-8.8, -2.4]) scores than controls; all p-values<0.001. Volumes of total brain tissue and other brain tissues and structures correlated positively with IQ and educational skills, a relationship that was similar for both the EP and controls. Total brain tissue volume explained between 20-40% of the IQ and educational outcome differences between EP and controls. CONCLUSIONS: EP adolescents had smaller brain volumes, lower IQs and poorer educational performance than controls. Brain volumes of multiple tissues and structures are related to IQ and educational outcomes. Smaller total brain tissue volume is an important contributor to the cognitive and educational underperformance of adolescents born EP.
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ItemPreventing academic difficulties in preterm children: a randomised controlled trial of an adaptive working memory training intervention - IMPRINT study(BMC, 2013-09-16)BACKGROUND: Very preterm children exhibit difficulties in working memory, a key cognitive ability vital to learning information and the development of academic skills. Previous research suggests that an adaptive working memory training intervention (Cogmed) may improve working memory and other cognitive and behavioural domains, although further randomised controlled trials employing long-term outcomes are needed, and with populations at risk for working memory deficits, such as children born preterm.In a cohort of extremely preterm (<28 weeks' gestation)/extremely low birthweight (<1000 g) 7-year-olds, we will assess the effectiveness of Cogmed in improving academic functioning 2 years' post-intervention. Secondary objectives are to assess the effectiveness of Cogmed in improving working memory and attention 2 weeks', 12 months' and 24 months' post-intervention, and to investigate training related neuroplasticity in working memory neural networks 2 weeks' post-intervention. METHODS/DESIGN: This double-blind, placebo-controlled, randomised controlled trial aims to recruit 126 extremely preterm/extremely low birthweight 7-year-old children. Children attending mainstream school without major intellectual, sensory or physical impairments will be eligible. Participating children will undergo an extensive baseline cognitive assessment before being randomised to either an adaptive or placebo (non-adaptive) version of Cogmed. Cogmed is a computerised working memory training program consisting of 25 sessions completed over a 5 to 7 week period. Each training session takes approximately 35 minutes and will be completed in the child's home. Structural, diffusion and functional Magnetic Resonance Imaging, which is optional for participants, will be completed prior to and 2 weeks following the training period. Follow-up assessments focusing on academic skills (primary outcome), working memory and attention (secondary outcomes) will be conducted at 2 weeks', 12 months' and 24 months' post-intervention. DISCUSSION: To our knowledge, this study will be the first randomised controlled trial to (a) assess the effectiveness of Cogmed in school-aged extremely preterm/extremely low birthweight children, while incorporating advanced imaging techniques to investigate neural changes associated with adaptive working memory training, and (b) employ long-term follow-up to assess the potential benefit of improved working memory on academic functioning. If effective, Cogmed would serve as a valuable, available intervention for improving developmental outcomes for this population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000124831.
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ItemAlterations in the optic radiations of very preterm children-Perinatal predictors and relationships with visual outcomes(ELSEVIER SCI LTD, 2014)Children born very preterm (VPT) are at risk for visual impairments, the main risk factors being retinopathy of prematurity and cerebral white matter injury, however these only partially account for visual impairments in VPT children. This study aimed to compare optic radiation microstructure and volume between VPT and term-born children, and to investigate associations between 1) perinatal variables and optic radiations; 2) optic radiations and visual function in VPT children. We hypothesized that optic radiation microstructure would be altered in VPT children, predicted by neonatal cerebral white matter abnormality and retinopathy of prematurity, and associated with visual impairments. 142 VPT children and 32 controls underwent diffusion-weighted magnetic resonance imaging at 7 years of age. Optic radiations were delineated using constrained spherical deconvolution tractography. Tract volume and average diffusion tensor values for the whole optic radiations and three sub-regions were compared between the VPT and control groups, and correlated with perinatal variables and 7-year visual outcome data. Total tract volumes and average diffusion values were similar between VPT and control groups. On regional analysis of the optic radiation, mean and radial diffusivity were higher within the middle sub-regions in VPT compared with control children. Neonatal white matter abnormalities and retinopathy of prematurity were associated with optic radiation diffusion values. Lower fractional anisotropy in the anterior sub-regions was associated with poor visual acuity and increased likelihood of other visual defects. This study presents evidence for microstructural alterations in the optic radiations of VPT children, which are largely predicted by white matter abnormality or severe retinopathy of prematurity, and may partially explain the higher rate of visual impairments in VPT children.
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ItemNeurobehaviour between birth and 40 weeks' gestation in infants born <30 weeks' gestation and parental psychological wellbeing: predictors of brain development and child outcomes(BMC, 2014-04-24)BACKGROUND: Infants born <30 weeks' gestation are at increased risk of long term neurodevelopmental problems compared with term born peers. The predictive value of neurobehavioural examinations at term equivalent age in very preterm infants has been reported for subsequent impairment. Yet there is little knowledge surrounding earlier neurobehavioural development in preterm infants prior to term equivalent age, and how it relates to perinatal factors, cerebral structure, and later developmental outcomes. In addition, maternal psychological wellbeing has been associated with child development. Given the high rate of psychological distress reported by parents of preterm children, it is vital we understand maternal and paternal wellbeing in the early weeks and months after preterm birth and how this influences the parent-child relationship and children's outcomes. Therefore this study aims to examine how 1) early neurobehaviour and 2) parental mental health relate to developmental outcomes for infants born preterm compared with infants born at term. METHODS/DESIGN: This prospective cohort study will describe the neurobehaviour of 150 infants born at <30 weeks' gestational age from birth to term equivalent age, and explore how early neurobehavioural deficits relate to brain growth or injury determined by magnetic resonance imaging, perinatal factors, parental mental health and later developmental outcomes measured using standardised assessment tools at term, one and two years' corrected age. A control group of 150 healthy term-born infants will also be recruited for comparison of outcomes. To examine the effects of parental mental health on developmental outcomes, both parents of preterm and term-born infants will complete standardised questionnaires related to symptoms of anxiety, depression and post-traumatic stress at regular intervals from the first week of their child's birth until their child's second birthday. The parent-child relationship will be assessed at one and two years' corrected age. DISCUSSION: Detailing the trajectory of infant neurobehaviour and parental psychological distress following very preterm birth is important not only to identify infants most at risk, further understand the parental experience and highlight potential times for intervention for the infant and/or parent, but also to gain insight into the effect this has on parent-child interaction and child development.
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ItemNeural Correlates of Impaired Vision in Adolescents Born Extremely Preterm and/or Extremely Low Birthweight(PUBLIC LIBRARY SCIENCE, 2014-03-24)BACKGROUND: Adolescents born extremely preterm (EP; <28 weeks' gestation) and/or extremely low birthweight (ELBW; <1000 g) experience high rates of visual impairments, however the potential neural correlates of visual impairments in EP/ELBW adolescents require further investigation. This study aimed to: 1) compare optic radiation and primary visual cortical structure between EP/ELBW adolescents and normal birthweight controls; 2) investigate associations between perinatal factors and optic radiation and primary visual cortical structure in EP/ELBW adolescents; 3) investigate associations between optic radiation and primary visual cortical structure in EP/ELBW adolescents and the odds of impaired vision. METHODS: 196 EP/ELBW adolescents and 143 controls underwent magnetic resonance imaging at a mean age of 18 years. Optic radiations were delineated using constrained spherical deconvolution based probabilistic tractography. Primary visual cortices were segmented using FreeSurfer software. Diffusion tensor variables and tract volume of the optic radiations, as well as volume, surface area and thickness of the primary visual cortices, were estimated. RESULTS: Axial, radial and mean diffusivities within the optic radiations, and primary visual cortical thickness, were higher in the EP/ELBW adolescents than controls. Within EP/ELBW adolescents, postnatal corticosteroid exposure was associated with altered optic radiation diffusion values and lower tract volume, while decreasing gestational age at birth was associated with increased primary visual cortical volume, area and thickness. Furthermore, decreasing optic radiation fractional anisotropy and tract volume, and increasing optic radiation diffusivity in EP/ELBW adolescents were associated with increased odds of impaired vision, whereas primary visual cortical measures were not associated with the odds of impaired vision. CONCLUSIONS: Optic radiation and primary visual cortical structure are altered in EP/ELBW adolescents compared with controls, with the greatest alterations seen in those exposed to postnatal corticosteroids and those born earliest. Structural alterations to the optic radiations may increase the risk of impaired vision in EP/ELBW adolescents.
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ItemHistologic chorioamnionitis in preterm infants: correlation with brain magnetic resonance imaging at term equivalent age(BIOMED CENTRAL LTD, 2018-02-15)BACKGROUND: To explore the associations between histologic chorioamnionitis with brain injury, maturation and size on magnetic resonance imaging (MRI) of preterm infants at term equivalent age. METHODS: Preterm infants (23-36 weeks' gestational age) were recruited into two longitudinal cohort studies. Presence or absence of chorioamnionitis was obtained from placental histology and clinical data were recorded. MRI at term-equivalent age was assessed for brain injury (intraventricular haemorrhage, cysts, signal abnormalities), maturation (degree of myelination, gyral maturation) and size of cerebral structures (metrics and brain segmentation). Histologic chorioamnionitis was assessed as a predictor of MRI variables using linear and logistic regression, with adjustment for confounding perinatal variables. RESULTS: Two hundred and twelve infants were included in this study, 47 (22%) of whom had histologic chorioamnionitis. Histologic chorioamnionitis was associated with higher odds of intraventricular haemorrhage (odds ratio [OR] (95% confidence interval [CI]) = 7.4 (2.4, 23.1)), less mature gyral maturation (OR (95% CI) = 2.0 (1.0, 3.8)) and larger brain volume (mean difference in cubic centimeter (95% CI) of 14.1 (1.9, 26.2)); but all relationships disappeared following adjustment for perinatal variables. CONCLUSION: Histologic chorioamnionitis was not independently associated with IVH, less mature gyral maturation or brain volume at term-equivalent age in preterm infants.