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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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    Neurobehaviour at term-equivalent age and neurodevelopmental outcomes at 2 years in infants born moderate-to-late preterm
    Spittle, AJ ; Walsh, JM ; Potter, C ; Mcinnes, E ; Olsen, JE ; Lee, KJ ; Anderson, PJ ; Doyle, LW ; Cheong, JLY (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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    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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    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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    Neonatal basal ganglia and thalamic volumes: very preterm birth and 7-year neurodevelopmental outcomes
    Loh, WY ; Anderson, PJ ; Cheong, JLY ; Spittle, AJ ; Chen, J ; Lee, KJ ; Molesworth, C ; Inder, TE ; Connelly, A ; Doyle, LW ; Thompson, DK (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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    Long term follow up of high risk children: who, why and how?
    Doyle, LW ; Anderson, PJ ; Battin, M ; Bowen, JR ; Brown, N ; Callanan, C ; Campbell, C ; Chandler, S ; Cheong, J ; Darlow, B ; Davis, PG ; DePaoli, T ; French, N ; McPhee, A ; Morris, S ; O'Callaghan, M ; Rieger, I ; Roberts, G ; Spittle, AJ ; Wolke, D ; Woodward, LJ (BMC, 2014-11-17)
    BACKGROUND: Most babies are born healthy and grow and develop normally through childhood. There are, however, clearly identifiable high-risk groups of survivors, such as those born preterm or with ill-health, who are destined to have higher than expected rates of health or developmental problems, and for whom more structured and specialised follow-up programs are warranted. DISCUSSION: This paper presents the results of a two-day workshop held in Melbourne, Australia, to discuss neonatal populations in need of more structured follow-up and why, in addition to how, such a follow-up programme might be structured. Issues discussed included the ages of follow-up, and the personnel and assessment tools that might be required. Challenges for translating results into both clinical practice and research were identified. Further issues covered included information sharing, best practice for families and research gaps. SUMMARY: A substantial minority of high-risk children has long-term medical, developmental and psychological adverse outcomes and will consume extensive health and education services as they grow older. Early intervention to prevent adverse outcomes and the effective integration of services once problems are identified may reduce the prevalence and severity of certain outcomes, and will contribute to an efficient and effective use of health resources. The shared long-term goal for families and professionals is to work toward ensuring that high risk children maximise their potential and become productive and valued members of society.
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    Neurobehaviour between birth and 40 weeks' gestation in infants born <30 weeks' gestation and parental psychological wellbeing: predictors of brain development and child outcomes
    Spittle, AJ ; Thompson, DK ; Brown, NC ; Treyvaud, K ; Cheong, JLY ; Lee, KJ ; Pace, CC ; Olsen, J ; Allinson, LG ; Morgan, AT ; Seal, M ; Eeles, A ; Judd, F ; Doyle, LW ; Anderson, PJ (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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    The Baby Moves prospective cohort study protocol: using a smartphone application with the General Movements Assessment to predict neurodevelopmental outcomes at age 2 years for extremely preterm or extremely low birthweight infants
    Spittle, AJ ; Olsen, J ; Kwong, A ; Doyle, LW ; Marschik, PB ; Einspieler, C ; Cheong, JLY (BMJ PUBLISHING GROUP, 2016)
    INTRODUCTION: Infants born extremely preterm (EP; <28 weeks' gestation) and/or with extremely low birth weight (ELBW; <1000 g birth weight) are at increased risk for adverse neurodevelopmental outcomes. However, it is challenging to predict those EP/ELBW infants destined to have long-term neurodevelopmental impairments in order to target early intervention to those in most need. The General Movements Assessment (GMA) in early infancy has high predictive validity for neurodevelopmental outcomes in preterm infants. However, access to a GMA may be limited by geographical constraints and a lack of GMA-trained health professionals. Baby Moves is a smartphone application (app) developed for caregivers to video and upload their infant's general movements to be scored remotely by a certified GMA assessor. The aim of this study is to determine the predictive ability of using the GMA via the Baby Moves app for neurodevelopmental impairment in infants born EP/ELBW. METHODS AND ANALYSIS: This prospective cohort study will recruit infants born EP/ELBW across the state of Victoria, Australia in 2016 and 2017. A control group of normal birth weight (>2500 g birth weight), term-born (≥37 weeks' gestation) infants will also be recruited as a local reference group. Parents will video their infant's general movements at two time points between 3 and 4 months' corrected age using the Baby Moves app. Videos will be scored by certified GMA assessors and classified as normal or abnormal. Parental satisfaction using the Baby Moves app will be assessed via survey. Neurodevelopmental outcome at 2 years' corrected age includes developmental delay according to the Bayley Scales of Infant and Toddler Development-III and cerebral palsy diagnosis. ETHICS AND DISSEMINATION: This study was approved by the Human Research and Ethics Committees at the Royal Children's Hospital, The Royal Women's Hospital, Monash Health and Mercy Health in Melbourne, Australia. Study findings will be disseminated via peer-reviewed publications and conference presentations.
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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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    Neonatal Brain Tissue Classification with Morphological Adaptation and Unified Segmentation
    Beare, RJ ; Chen, J ; Kelly, CE ; Alexopoulos, D ; Smyser, CD ; Rogers, CE ; Loh, WY ; Matthews, LG ; Cheong, JLY ; Spittle, AJ ; Anderson, PJ ; Doyle, LW ; Inder, TE ; Seal, ML ; Thompson, DK (FRONTIERS MEDIA SA, 2016-03-29)
    Measuring the distribution of brain tissue types (tissue classification) in neonates is necessary for studying typical and atypical brain development, such as that associated with preterm birth, and may provide biomarkers for neurodevelopmental outcomes. Compared with magnetic resonance images of adults, neonatal images present specific challenges that require the development of specialized, population-specific methods. This paper introduces MANTiS (Morphologically Adaptive Neonatal Tissue Segmentation), which extends the unified segmentation approach to tissue classification implemented in Statistical Parametric Mapping (SPM) software to neonates. MANTiS utilizes a combination of unified segmentation, template adaptation via morphological segmentation tools and topological filtering, to segment the neonatal brain into eight tissue classes: cortical gray matter, white matter, deep nuclear gray matter, cerebellum, brainstem, cerebrospinal fluid (CSF), hippocampus and amygdala. We evaluated the performance of MANTiS using two independent datasets. The first dataset, provided by the NeoBrainS12 challenge, consisted of coronal T 2-weighted images of preterm infants (born ≤30 weeks' gestation) acquired at 30 weeks' corrected gestational age (n = 5), coronal T 2-weighted images of preterm infants acquired at 40 weeks' corrected gestational age (n = 5) and axial T 2-weighted images of preterm infants acquired at 40 weeks' corrected gestational age (n = 5). The second dataset, provided by the Washington University NeuroDevelopmental Research (WUNDeR) group, consisted of T 2-weighted images of preterm infants (born <30 weeks' gestation) acquired shortly after birth (n = 12), preterm infants acquired at term-equivalent age (n = 12), and healthy term-born infants (born ≥38 weeks' gestation) acquired within the first 9 days of life (n = 12). For the NeoBrainS12 dataset, mean Dice scores comparing MANTiS with manual segmentations were all above 0.7, except for the cortical gray matter for coronal images acquired at 30 weeks. This demonstrates that MANTiS' performance is competitive with existing techniques. For the WUNDeR dataset, mean Dice scores comparing MANTiS with manually edited segmentations demonstrated good agreement, where all scores were above 0.75, except for the hippocampus and amygdala. The results show that MANTiS is able to segment neonatal brain tissues well, even in images that have brain abnormalities common in preterm infants. MANTiS is available for download as an SPM toolbox from http://developmentalimagingmcri.github.io/mantis.