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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ItemA simple screen performed at school entry can predict academic under-achievement at age seven in children born very preterm(WILEY, 2016-07)AIM: We aimed to compare the academic outcomes of a cohort of children born very preterm (VPT, <32 weeks of gestation) and children born at term at age 7 years and assess the ability of a pre-academic skill screen at age five to predict later academic impairment in children born VPT at age seven. METHODS: One hundred ninety-four children born VPT (born with either gestational age <30 weeks or birthweight <1250 g) and 70 controls born at term from a prospective birth cohort were compared on academic outcomes (Wide Range Achievement Test, WRAT4) at age seven using regression analyses. Receiver-operating characteristic curves were used to determine whether pre-academic skills (Kaufman Survey of Early Academic and Language Skills, K-SEALS) at age five predicted academic impairment at age seven in 174 of the VPT cohort. RESULTS: At the age of 7 years, children born VPT had lower mean word reading (-9.7, 95% CI: -14.7 to -4.6), spelling (-8.3, 95% CI: -13.3 to -3.3) and math computation (-10.9, 95% CI: -15.3 to -6.5) scores (all P-values ≤0.001) compared with controls born at term, even after adjusting for social risk and time since school commencement. In terms of pre-academic screening, the Numbers, Letters and Words subtest of the K-SEALS had adequate sensitivity and specificity (70-80%) for predicting children with academic impairment at age seven. CONCLUSIONS: Children born VPT underperformed in academic outcomes at age seven compared with controls born at term. A pre-academic screening tool used at school entry can predict children born VPT at risk of academic impairment at age seven who could benefit from targeted early intervention.
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ItemVery preterm children at risk for developmental coordination disorder have brain alterations in motor areas(WILEY, 2019-09)AIM: Brain alterations in very preterm children at risk for developmental coordination disorder were investigated. METHODS: Infants born very preterm with gestation age <30 weeks or birthweight <1250 g were recruited from Royal Women's Hospital Melbourne from 2001 to 2003. Volumetric imaging was performed at term equivalent age; at seven years, volumetric imaging and diffusion tensor imaging were performed. At seven years, 53 of 162 children without cerebral palsy had scores ≤16th percentile on the Movement Assessment Battery for Children-Second Edition and were considered at risk for developmental coordination disorder. RESULTS: At term equivalent age, smaller brain volumes were found for total brain tissue, cortical grey matter, cerebellum, caudate accumbens, pallidum and thalamus in children at risk for developmental coordination disorder (p < 0.05); similar patterns were present at seven years. There was no evidence for catch-up brain growth in at-risk children. At seven years, at-risk children displayed altered microstructural organisation in many white matter tracts (p < 0.05). CONCLUSION: Infants born very preterm at risk for developmental coordination disorder displayed smaller brain volumes at term equivalent age and seven years, and altered white matter microstructure at seven years, particularly in motor areas. There was no catch-up growth from infancy to seven years.
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ItemBrain structure and neurological and behavioural functioning in infants born preterm(WILEY, 2019-07)AIM: To examine: (1) relationships between brain structure, and concurrently assessed neurological and behavioural functioning, in infants born preterm at term-equivalent age (TEA; approximately 38-44wks); and (2) whether brain structure-function relationships differ between infants born very (24-29wks) and moderate-late (32-36wks) preterm. METHOD: A total of 257 infants (91 very preterm, 166 moderate-late preterm; 120 males, 137 females) had structural magnetic resonance imaging (MRI) and neurological and behavioural assessments (Prechtl's general movements assessment, Neonatal Intensive Care Unit Network Neurobehavioral Scale [NNNS] and Hammersmith Neonatal Neurological Examination [HNNE]). Two hundred and sixty-three infants (90 very preterm, 173 moderate-late preterm; 131 males, 132 females) had diffusion MRI and assessments. Associations were investigated between assessment scores and global brain volumes using linear regressions, regional brain volumes using Voxel-Based Morphometry, and white matter microstructure using Tract-Based Spatial Statistics. RESULTS: Suboptimal scores on some assessments were associated with lower fractional anisotropy and/or higher axial, radial, and mean diffusivities in some tracts: NNNS attention and reflexes, and HNNE total score and tone, were associated with the corpus callosum and optic radiation; NNNS quality of movement with the corona radiata; HNNE abnormal signs with several major tracts. Brain structure-function associations generally did not differ between the very and moderate-late preterm groups. INTERPRETATION: White matter microstructural alterations may be associated with suboptimal neurological and behavioural performance in some domains at TEA in infants born preterm. Brain structure-function relationships are similar for infants born very preterm and moderate-late preterm. WHAT THIS PAPER ADDS: Brain volume is not related to neurological/behavioural function in infants born preterm at term. White matter microstructure is related to some neurological/behavioural domains at term. Brain-behaviour relationships are generally similar for infants born very preterm and moderate-late preterm.
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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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ItemNo Preview AvailableDiffusion tractography and neuromotor outcome in very preterm children with white matter abnormalities(NATURE PUBLISHING GROUP, 2014-07)BACKGROUND: Moderate-to-severe white matter abnormality (WMA) in the newborn has been shown to produce persistent disruptions in cerebral connectivity but does not universally result in neurodevelopmental disability in very preterm (VPT) children. The aims of this hypothesis-driven study were to apply diffusion imaging to: (i) examine whether bilateral WMA detected in VPT children in the newborn period can predict microstructural organization at the age of 7 y and (ii) compare corticospinal tract and corpus callosum (CC) measures in VPT children at the age of 7 y with neonatal WMA with normal vs. impaired motor functioning. METHODS: Diffusion parameters of the corticospinal tract and CC were compared between VPT 7-y olds with (n = 20) and without (n = 42) bilateral WMA detected in the newborn period. For those with WMA, diffusion parameters were further examined. RESULTS: Microstructural organization of corticospinal tract and CC tracts at the age of 7 y were altered in VPT children with moderate-to-severe WMA detected at term equivalent age as compared with those without injury. Furthermore, diffusion parameters differed in the CC for children with WMA categorized by motor outcome (n = 8). CONCLUSION: WMA on conventional magnetic resonance imaging at term equivalent age is associated with altered microstructural organization of the corticospinal tract and CC at 7 y of age.
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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.