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    Preterm and term-equivalent age general movements and 1-year neurodevelopmental outcomes for infants born before 30weeks' gestation
    Olsen, JE ; Allinson, LG ; Doyle, LW ; Brown, NC ; Lee, KJ ; Eeles, AL ; Cheong, JLY ; Spittle, AJ (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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    Very preterm children at risk for developmental coordination disorder have brain alterations in motor areas
    Dewey, D ; Thompson, DK ; Kelly, CE ; Spittle, AJ ; Cheong, JLY ; Doyle, LW ; Anderson, PJ (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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    Brain structure and neurological and behavioural functioning in infants born preterm
    Kelly, CE ; Thompson, DK ; Cheong, JLY ; Chen, J ; Olsen, JE ; Eeles, AL ; Walsh, JM ; Seal, ML ; Anderson, PJ ; Doyle, LW ; Spittle, AJ (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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    Spontaneous infant movements that predict later cerebral palsy: reply to Hadders-Algra and Philippi
    Kwong, AKL ; Olsen, JE ; FitzGerald, TL ; Doyle, LW ; Cheong, JLY ; Spittle, AJ (WILEY, 2018-12)
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    The Baby Moves smartphone app for General Movements Assessment: Engagement amongst extremely preterm and term-born infants in a state-wide geographical study
    Kwong, AKL ; Eeles, AL ; Olsen, JE ; Cheong, JLY ; Doyle, LW ; Spittle, AJ (WILEY, 2019-05)
    AIM: The Baby Moves smartphone application is designed for parents to video their infants' spontaneous movement for remote General Movements Assessment (GMA). We aimed to assess the engagement with Baby Moves amongst high- and low-risk infants' families and the socio-demographic variables related to engagement. METHODS: Families of extremely preterm (EP; <28 weeks' gestational age) or extremely low-birthweight (ELBW; <1000 g) infants and term-born controls from a state-wide geographical cohort study were asked to download Baby Moves. Baby Moves provided reminders and instructions to capture videos of their infants' general movements. Parents were surveyed about Baby Moves' usability. RESULTS: The parents of 451 infants (226 EP/ELBW; 225 control) were recruited; 416 (204 EP/ELBW; 212 control) downloaded Baby Moves, and 346 (158 EP/ELBW; 188 control) returned at least one scorable video for remote GMA. Fewer EP/ELBW families submitted a scorable video than controls (70 vs. 83%, respectively; odds ratio (OR) 0.48, 95% confidence interval (CI) 0.3-0.79, P = 0.003), but the difference diminished when adjusted for socio-demographic variables (OR 1.09, 95% CI 0.59-2.0, P = 0.79). Families who received government financial support (OR 0.28, 95% CI 0.1-0.78, P = 0.015), who spoke limited English at home (OR 0.39, 95% CI 0.22-0.69, P = 0.001) or with lower maternal education (OR 0.38, 95% CI 0.21-0.68, P = 0.001) were less likely to return a scorable video. Surveyed parents responded mostly positively to Baby Moves' usability. CONCLUSIONS: Most parents in this study successfully used Baby Moves to capture infant movements for remote GMA. Families of lower socio-demographic status used Baby Moves less.
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    Predictive validity of spontaneous early infant movement for later cerebral palsy: a systematic review
    Kwong, AKL ; Fitzgerald, TL ; Doyle, LW ; Cheong, JLY ; Spittle, AJ (WILEY, 2018-05)
    AIM: To systematically review the predictive validity of spontaneous early infant movements for later cerebral palsy (CP). METHOD: Cohort studies with published data to calculate predictive validity of early spontaneous movements for later CP were searched in four electronic databases: CINAHL, Embase, MEDLINE, and PsycINFO. RESULTS: Forty-seven studies met inclusion criteria. The Prechtl General Movements Assessment (GMA) during the fidgety period (10-20wks corrected age) had the strongest sensitivity: 97 per cent (95% confidence interval [CI] 93-99) and specificity: 89% (95% CI 83-93). The sensitivity and specificity of the Prechtl GMA during the writhing period (birth-6wks) was 93% (95% CI 86-96) and 59% (95% CI 45-71) respectively. Cramped-synchronized movements in the writhing period according to Prechtl had the best specificity (sensitivity: 70% [95% CI 54-82]; specificity: 97% [95% CI 74-100]). Hadders-Algra's method of assessing general movements had a pooled sensitivity and specificity of 89% (95% CI 66-97) and 81% (95% CI 64-91) respectively. Presence of asymmetric postures and movement quality/quantity were reported under the Hammersmith Infant Neurological Examination, Hammersmith Neonatal Neurological Examination, and Movement Assessment of Infants but had weak associations with later CP. INTERPRETATION: Fidgety movements assessed by the Prechtl GMA have the strongest predictive validity for later CP, but cannot be considered in isolation because of the presence of false positive results. WHAT THIS PAPER ADDS: Fidgety general movements (Prechtl) are most predictive for later cerebral palsy compared with other spontaneous movements. False positive results are high among all spontaneous movement assessments.
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    Histologic chorioamnionitis in preterm infants: correlation with brain magnetic resonance imaging at term equivalent age
    Granger, C ; Spittle, AJ ; Walsh, J ; Pyman, J ; Anderson, PJ ; Thompson, DK ; Lee, KJ ; Coleman, L ; Dagia, C ; Doyle, LW ; Cheong, J (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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    Impact 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
    Cheong, JLY ; Wark, JD ; Cheung, MM ; Irving, L ; Burnett, AC ; Lee, KJ ; Garland, SM ; Smallwood, D ; Patton, GC ; Haikerwal, A ; Doyle, LW ; Cheong, J ; Anderson, C ; Anderson, P ; Bear, M ; Boland, R ; Burnett, A ; Callanan, C ; Carse, E ; Charlton, M ; Clarke, M ; Courtot, J ; Davis, N ; Doyle, L ; Duff, J ; Ellis, R ; Haikerwal, A ; Hickey, L ; Hayes, M ; Josev, E ; Kelly, E ; McDonald, M ; McInnes, E ; Novella, B ; Olsen, J ; Opie, G ; Roberts, G ; Scott, K ; Spittle, A ; Stevens, P ; Turner, A-M (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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    Desikan-Killiany-Tourville Atlas Compatible Version of M-CRIB Neonatal Parcellated Whole Brain Atlas: The M-CRIB 2.0
    Alexander, B ; Loh, WY ; Matthews, LG ; Murray, AL ; Adamson, C ; Beare, R ; Chen, J ; Kelly, CE ; Anderson, PJ ; Doyle, LW ; Spittle, AJ ; Cheong, JLY ; Seal, ML ; Thompson, DK (FRONTIERS MEDIA SA, 2019-02-05)
    Our recently published M-CRIB atlas comprises 100 neonatal brain regions including 68 compatible with the widely-used Desikan-Killiany adult cortical atlas. A successor to the Desikan-Killiany atlas is the Desikan-Killiany-Tourville atlas, in which some regions with unclear boundaries were removed, and many existing boundaries were revised to conform to clearer landmarks in sulcal fundi. Our first aim here was to modify cortical M-CRIB regions to comply with the Desikan-Killiany-Tourville protocol, in order to offer: (a) compatibility with this adult cortical atlas, (b) greater labeling accuracy due to clearer landmarks, and (c) optimisation of cortical regions for integration with surface-based infant parcellation pipelines. Secondly, we aimed to update subcortical regions in order to offer greater compatibility with subcortical segmentations produced in FreeSurfer. Data utilized were the T2-weighted MRI scans in our M-CRIB atlas, for 10 healthy neonates (post-menstrual age at MRI 40-43 weeks, four female), and corresponding parcellated images. Edits were performed on the parcellated images in volume space using ITK-SNAP. Cortical updates included deletion of frontal and temporal poles and 'Banks STS,' and modification of boundaries of many other regions. Changes to subcortical regions included the addition of 'ventral diencephalon,' and deletion of 'subcortical matter' labels. A detailed updated parcellation protocol was produced. The resulting whole-brain M-CRIB 2.0 atlas comprises 94 regions altogether. This atlas provides comparability with adult Desikan-Killiany-Tourville-labeled cortical data and FreeSurfer-labeed subcortical data, and is more readily adaptable for incorporation into surface-based neonatal parcellation pipelines. As such, it offers the ability to help facilitate a broad range of investigations into brain structure and function both at the neonatal time point and developmentally across the lifespan.
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    Characterisation of brain volume and microstructure at term-equivalent age in infants born across the gestational age spectrum
    Thompson, DK ; Kelly, CE ; Chen, J ; Beare, R ; Alexander, B ; Seal, ML ; Lee, KJ ; Matthews, LG ; Anderson, PJ ; Doyle, LW ; Cheong, JLY ; Spittle, AJ (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.