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    The role of social risk in an early preventative care programme for infants born very preterm: a randomized controlled trial
    Spittle, AJ ; Treyvaud, K ; Lee, KJ ; Anderson, PJ ; Doyle, LW (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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    Predictive value of the Movement Assessment Battery for Children - Second Edition at 4years, for motor impairment at 8years in children born preterm
    Griffiths, A ; Morgan, P ; Anderson, PJ ; Doyle, LW ; Lee, KJ ; Spittle, AJ (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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    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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    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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    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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    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.
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    Accuracy of Two Motor Assessments during the First Year of Life in Preterm Infants for Predicting Motor Outcome at Preschool Age
    Spittle, AJ ; Lee, KJ ; Spencer-Smith, M ; Lorefice, LE ; Anderson, PJ ; Doyle, LW ; Parikh, NA (PUBLIC LIBRARY SCIENCE, 2015-05-13)
    AIM: The primary aim of this study was to investigate the accuracy of the Alberta Infant Motor Scale (AIMS) and Neuro-Sensory Motor Developmental Assessment (NSMDA) over the first year of life for predicting motor impairment at 4 years in preterm children. The secondary aims were to assess the predictive value of serial assessments over the first year and when using a combination of these two assessment tools in follow-up. METHOD: Children born <30 weeks' gestation were prospectively recruited and assessed at 4, 8 and 12 months' corrected age using the AIMS and NSMDA. At 4 years' corrected age children were assessed for cerebral palsy (CP) and motor impairment using the Movement Assessment Battery for Children 2nd-edition (MABC-2). We calculated accuracy of the AIMS and NSMDA for predicting CP and MABC-2 scores ≤15th (at-risk of motor difficulty) and ≤5th centile (significant motor difficulty) for each test (AIMS and NSMDA) at 4, 8 and 12 months, for delay on one, two or all three of the time points over the first year, and finally for delay on both tests at each time point. RESULTS: Accuracy for predicting motor impairment was good for each test at each age, although false positives were common. Motor impairment on the MABC-2 (scores ≤5th and ≤15th) was most accurately predicted by the AIMS at 4 months, whereas CP was most accurately predicted by the NSMDA at 12 months. In regards to serial assessments, the likelihood ratio for motor impairment increased with the number of delayed assessments. When combining both the NSMDA and AIMS the best accuracy was achieved at 4 months, although results were similar at 8 and 12 months. INTERPRETATION: Motor development during the first year of life in preterm infants assessed with the AIMS and NSMDA is predictive of later motor impairment at preschool age. However, false positives are common and therefore it is beneficial to follow-up children at high risk of motor impairment at more than one time point, or to use a combination of assessment tools. TRIAL REGISTRATION: ACTR.org.au ACTRN12606000252516.