Obstetrics and Gynaecology - Research Publications
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ItemPreterm and term-equivalent age general movements and 1-year neurodevelopmental outcomes for infants born before 30weeks' gestation(WILEY, 2018-01)AIM: To examine the associations between Prechtl's General Movements Assessment (GMA), conducted from birth to term-equivalent age, and neurodevelopmental outcomes at 12 months corrected age, in infants born very preterm. METHOD: One hundred and thirty-seven infants born before 30 weeks' gestation had serial GMA (categorized as 'normal' or 'abnormal') before term and at term-equivalent age. At 12 months corrected age, neurodevelopment was assessed using the Alberta Infant Motor Scale (AIMS); Neurological, Sensory, Motor, Developmental Assessment (NSMDA); and Touwen Infant Neurological Examination (TINE). The relationships between GMA at four time points and 12-month neurodevelopmental assessments were examined using regression models. RESULTS: Abnormal GMA at all time points were associated with worse continuous scores on the AIMS, NSMDA, and TINE (p<0.05). Abnormal GMA before term and at term-equivalent age were associated with increased odds of mild-severe dysfunction on the NSMDA (odds ratio [OR] 4.26, 95% confidence interval [CI] 1.55-11.71, p<0.01; and OR 4.16, 95% CI 1.55-11.17, p<0.01 respectively) and abnormal GMA before term with increased odds of suboptimal-abnormal motor function on the TINE (OR 2.75, 95% CI 1.10-6.85, p=0.03). INTERPRETATION: Abnormal GMA before term and at term-equivalent age were associated with worse neurodevelopment at 12 months corrected age in children born very preterm. WHAT THIS PAPER ADDS: Abnormal general movements before term predict developmental deficits at 1 year in infants born very preterm. General Movements Assessment before term identifies at-risk infants born very preterm.
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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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ItemNo Preview AvailableNeonatal basal ganglia and thalamic volumes: very preterm birth and 7-year neurodevelopmental outcomes(NATURE PUBLISHING GROUP, 2017-12)BackgroundThis study aims to (i) compare volumes of individual basal ganglia nuclei (caudate nucleus, pallidum, and putamen) and the thalamus between very preterm (VP) and term-born infants at term-equivalent age; (ii) explore neonatal basal ganglia and thalamic volume relationships with 7-year neurodevelopmental outcomes, and whether these relationships differed between VP and term-born children.Methods210 VP (<30 weeks' gestational age) and 39 term-born (≥37 weeks' gestational age) infants underwent brain magnetic resonance imaging at term-equivalent age, and deep gray matter volumes of interest were automatically generated. 186 VP and 37 term-born children were assessed for a range of neurodevelopmental measures at age 7 years.ResultsAll deep gray matter structures examined were smaller in VP infants compared with controls at term-equivalent age; ranging from (percentage mean difference (95% confidence intervals) -6.2% (-10.2%, -2.2%) for the putamen, to -9.5% (-13.9%, -5.1%) for the caudate nucleus. Neonatal basal ganglia and thalamic volumes were positively related to motor, intelligence quotient, and academic outcomes at age 7 years, with mostly similar relationships in the VP and control groups.ConclusionVP birth results in smaller basal ganglia and thalamic volumes at term-equivalent age, and these smaller volumes are related to a range of 7-year neurodevelopmental deficits in VP children.
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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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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.
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ItemImpact of extreme prematurity or extreme low birth weight on young adult health and well-being: the Victorian Infant Collaborative Study (VICS) 1991-1992 Longitudinal Cohort study protocol(BMJ PUBLISHING GROUP, 2019-05)INTRODUCTION: Infants born extremely preterm (EP, <28 weeks' gestation) or with extremely low birth weight (ELBW,<1000 g) in the era when surfactant has been available clinically are at high risk of health and developmental problems in childhood and adolescence. However, how their health and well-being may be affected in adulthood is not well known. This study aims to compare between EP/ELBW and normal birthweight (NBW) controls: (1) physical health, mental health and socioemotional functioning at 25 years of age and (2) trajectories of these outcomes from childhood to adulthood. In addition, this study aims to identify risk factors in pregnancy, infancy, childhood and adolescence for poor physical health and well-being in EP/ELBW young adults. METHODS AND ANALYSIS: The Victorian Infant Collaborative Study (VICS) is a prospective geographical cohort of all EP/ELBW survivors to 18 years of age born in the State of Victoria, Australia, from 1 January 1991 to 31 December 1992 (n=297) and contemporaneous term-born/NBW controls (n=262). Participants were recruited at birth and followed up at 2, 5, 8 and 18 years. This 25-year follow-up includes assessments of physical health (cardiovascular, respiratory and musculoskeletal), mental health and socioemotional functioning. Outcomes will be compared between the birth groups using linear and logistic regression, fitted using generalised estimating equations (GEEs). Trajectories of health outcomes from early childhood will be compared between the birth groups using linear mixed-effects models. Risk factors for adult outcomes will be assessed using linear and logistic regression (fitted using GEEs). ETHICS AND DISSEMINATION: This study was approved by the Human Research Ethics Committees of the Royal Women's Hospital, Mercy Hospital for Women, Monash Medical Centre and the Royal Children's Hospital, Melbourne. Study outcomes will be disseminated through conference presentations, peer-reviewed publications, the internet and social media.
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ItemCharacterisation of brain volume and microstructure at term-equivalent age in infants born across the gestational age spectrum(ELSEVIER SCI LTD, 2019)BACKGROUND: Risk of morbidity differs between very preterm (VP; <32 weeks' gestational age (GA)), moderate preterm (MP; 32-33 weeks' GA), late preterm (LP; 34-36 weeks' GA), and full-term (FT; ≥37 weeks' GA) infants. However, brain structure at term-equivalent age (TEA; 38-44 weeks) remains to be characterised in all clinically important GA groups. We aimed to compare global and regional brain volumes, and regional white matter microstructure, between VP, MP, LP and FT groups at TEA, in order to establish the magnitude and anatomical locations of between-group differences. METHODS: Structural images from 328 infants (91 VP, 63 MP, 104 LP and 70 FT) were segmented into white matter, cortical grey matter, cerebrospinal fluid (CSF), subcortical grey matter, brainstem and cerebellum. Global tissue volumes were analysed, and additionally, cortical grey matter and white matter volumes were analysed at the regional level using voxel-based morphometry. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) images from 361 infants (92 VP, 69 MP, 120 LP and 80 FT) were analysed using Tract-Based Spatial Statistics. Statistical analyses involved examining the overall effect of GA group on global volumes (using linear regressions) and regional volumes and microstructure (using non-parametric permutation testing), as well performing post-hoc comparisons between the GA sub-groups. RESULTS: On global analysis, cerebrospinal fluid (CSF) volume was larger in all preterm sub-groups compared with the FT group. On regional analysis, volume was smaller in parts of the temporal cortical grey matter, and parts of the temporal white matter and corpus callosum, in all preterm sub-groups compared with the FT group. FA was lower, and RD and MD were higher in voxels located in much of the white matter in all preterm sub-groups compared with the FT group. The anatomical locations of group differences were similar for each preterm vs. FT comparison, but the magnitude and spatial extent of group differences was largest for the VP, followed by the MP, and then the LP comparison. Comparing within the preterm groups, the VP sub-group had smaller frontal and temporal grey and white matter volume, and lower FA and higher MD and RD within voxels in the approximate location of the corpus callosum compared with the MP sub-group. There were few volume and microstructural differences between the MP and LP sub-groups. CONCLUSION: All preterm sub-groups had atypical brain volume and microstructure at TEA when compared with a FT group, particularly for the CSF, temporal grey and white matter, and corpus callosum. In general, the groups followed a gradient, where the differences were most pronounced for the VP group, less pronounced for the MP group, and least pronounced for the LP group. The VP sub-group was particularly vulnerable compared with the MP and LP sub-groups.
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ItemCaffeine for apnea of prematurity and brain development at 11years of age(WILEY, 2018-09)OBJECTIVE: Caffeine therapy for apnea of prematurity has been reported to improve brain white matter microstructure at term-equivalent age, but its long-term effects are unknown. This study aimed to investigate whether caffeine affects (1) brain structure at 11 years of age, and (2) brain development from term-equivalent age to 11 years of age, compared with placebo. METHODS: Preterm infants born ≤1250 g were randomly allocated to caffeine or placebo. Magnetic resonance imaging (MRI) was performed on 70 participants (33 caffeine, 37 placebo) at term-equivalent age and 117 participants (63 caffeine, 54 placebo) at 11 years of age. Global and regional brain volumes and white matter microstructure were measured at both time points. RESULTS: In general, there was little evidence for differences between treatment groups in brain volumes or white matter microstructure at age 11 years. There was, however, evidence that the caffeine group had a smaller corpus callosum than the placebo group. Volumetric brain development from term-equivalent to 11 years of age was generally similar between treatment groups. However, there was evidence that caffeine was associated with slower growth of the corpus callosum, and slower decreases in axial, radial, and mean diffusivities in the white matter, particularly at the level of the centrum semiovale, over time than placebo. INTERPRETATION: This study suggests any benefits of neonatal caffeine therapy on brain structure in preterm infants weaken over time and are not clearly detectable by MRI at age 11 years, although caffeine may have long-term effects on corpus callosum development.