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OBJECTIVES: To adapt and develop a reliable and easily administered outcome measure of physical and respiratory function in critically ill children in the PICU. DESIGN: Modified Delphi study to adapt the Chelsea Critical Care Physical Assessment (CPAx) tool for use in children 2-18 years old, with subsequent prospective testing in a single-center cohort. SETTING: Single-center tertiary PICU. SUBJECTS: Delphi process in 27 panelists (including physiotherapists, occupational therapists, and pediatric intensivists from seven countries from January 2018 to March 2018). Cohort study in 54 patients admitted to PICU for greater than 24 hours over a 3-month period (April 2018 to June 2018), with median age 5.5 years (interquartile range [IQR], 3-12.75 yr), 33 of 54 male, and 38 of 54 invasively ventilated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three Delphi iterations were required to reach greater than or equal to 80% consensus in all the children's CPAx (cCPAx) items. In the subsequent cohort study, six physiotherapists used the cCPAx tool and scored 54 participants, with a total 106 observations. The median cCPAx tool score was 14.50 (IQR, 3-25) out of a possible total of 50. Inter-rater reliability for 30 randomly selected participants was excellent (intraclass correlation coefficient, 0.998). Completion rate of cCPAx in the 54 patients occurred in 78 of 106 occasions (74%). CONCLUSIONS: The cCPAx tool content that was developed using Delphi methodology provided a feasible and clinically relevant tool for use in assessing physical morbidity in PICU patients 2-18 years old. Overall, the cCPAx scores were low, demonstrating low levels of physical function and high levels of immobility during PICU care.
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Cuidados Críticos , Técnica Delphi , Unidades de Terapia Intensiva Pediátrica , Humanos , Pré-Escolar , Masculino , Adolescente , Criança , Feminino , Cuidados Críticos/métodos , Estudos Prospectivos , Estado Terminal/terapia , Reprodutibilidade dos Testes , Exame Físico/métodos , Desempenho Físico FuncionalRESUMO
BACKGROUND: To determine the diagnostic accuracy of Hammersmith Neonatal Neurological Examination (HNNE) at 30-32 weeks postmenstrual age (PMA, 'Early') and term equivalent age (TEA) in infants born <31 weeks PMA to predict cognitive outcomes at 12 months corrected age (CA). METHODS: Prospective cohort study of 119 infants (73 males; median 28.4 weeks gestational age at birth) who underwent Early and TEA HNNE. At 12 months CA, 104 participants completed Bayley Scales of Infant and Toddler Development, 3rd Edition, (Bayley-III). Optimum cut-off points for each HNNE subscale were determined to establish diagnostic accuracy for predicting adverse cognitive outcomes on the Bayley-III Cognitive Composite Scale (≤85). RESULTS: The best diagnostic accuracy for HNNE total score at 30-32 weeks PMA predicting cognitive impairment occurred at cut-off ≤16.7 (sensitivity (Se) = 71%, specificity (Sp) = 51%). The Abnormal Signs subscale demonstrated the best balance of sensitivity/specificity combination (Se = 71%, Sp = 71%; cut-off ≤1.5). For HNNE at TEA, the total score at cut-off ≤24.5 had Se = 71% and Sp = 47% for predicting cognitive impairment. The Tone Patterns subscale demonstrated the strongest diagnostic accuracy at TEA (Se = 71%, Sp = 63%; cut-off ≤3). CONCLUSIONS: Early and TEA HNNE demonstrated moderate diagnostic accuracy for cognitive outcomes at 12-months CA in infants born <31 weeks gestational age. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry; Trial Registration Number: ACTRN12613000280707; web address of trial: http://www.ANZCTR.org.au/ACTRN12613000280707.aspx . IMPACT: Early Hammersmith Neonatal Neurological Examination (HNNE) assessment at 30-32 weeks postmenstrual age has moderate diagnostic accuracy for cognitive outcomes at 12 months corrected age in infants born <31 weeks gestation. Early HNNE at 30-32 weeks has stronger predictive validity than HNNE at term equivalent age. Early HNNE may provide an early marker for risk-stratification to optimise the planning of post-discharge support and follow-up services for infants born preterm.
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Assistência ao Convalescente , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Feminino , Humanos , Lactente , Estudos Prospectivos , Austrália , Alta do Paciente , Exame Neurológico , Idade Gestacional , Retardo do Crescimento Fetal , Cognição , Desenvolvimento InfantilRESUMO
AIM: To evaluate the predictive validity of the Hammersmith Neonatal Neurological Examination (HNNE) performed early (at 32 weeks postmenstrual age) and at term-equivalent age (TEA) for 12-month motor outcomes in infants born very preterm. METHOD: This was a diagnostic study using data from a prospective birth cohort. A total of 104 infants born preterm at less than 31 weeks gestational age (males n = 61; mean = 28 weeks 1 day [SD 1 week 6 days], range 23 weeks 1 day-30 weeks 6 days) underwent HNNE early and at TEA, which were scored by comparison with term data. Motor outcomes at 12 months corrected age were determined using the Bayley Scales of Infant and Toddler Development, Third Edition (scores ≤85). Cut-off points were determined using receiver operating characteristic curves. RESULTS: Sixteen (15%) infants born preterm had motor impairment at 12 months corrected age. The HNNE total score cut-off points with the best combination of sensitivity and specificity at early and TEA assessments were 15.2 or lower (sensitivity 77%, 95% confidence interval [CI] = 46%-95%; specificity 74%, 95% CI = 63%-83%) and 23.5 or lower (sensitivity 67%, 95% CI = 38%-88%; specificity 66%, 95% CI = 54%-76%) respectively. The most predictive subscale at the early assessment was reflexes (sensitivity 86%, 95% CI = 57%-98%; specificity 62%, 95% CI = 51%-72%; cut-off point ≤3); at TEA, it was spontaneous movements (sensitivity 73%, 95% CI = 45%-92%; specificity 60%, 95% CI = 48%-70%; cut-off point ≤2). INTERPRETATION: The HNNE provides moderate predictive accuracy for motor outcome at 12 months corrected age in infants born very preterm. Although modest at both time points, early assessment had stronger predictive ability for motor outcomes than TEA when scored using term data, highlighting the value of performing the HNNE earlier in the neonatal period. Performing HNNE earlier may assist risk stratification when planning follow-up services.
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Desenvolvimento Infantil , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Humanos , Lactente , Feminino , Estudos Prospectivos , Exame Neurológico , Idade GestacionalRESUMO
BACKGROUND: This study aimed to identify which MRI and clinical assessments, alone or in combination, from (i) early (32 weeks postmenstrual age, PMA), (ii) term equivalent age (TEA) and (iii) 3 months corrected age (CA) are associated with motor or cognitive outcomes at 2 years CA in infants born <31 weeks gestation. METHODS: Prospective cohort study of 98 infants who underwent early and TEA MRI (n = 59 males; median birth gestational age 28 + 5 weeks). Hammersmith Neonatal Neurological Examination (HNNE), NICU Neonatal Neurobehavioural Scale and General Movements Assessment (GMs) were performed early and at TEA. Premie-Neuro was performed early and GMs, Test of Infant Motor Performance and visual assessment were performed at TEA and 3 months CA. Neurodevelopmental outcomes were determined using Bayley Scales of Infant and Toddler Development 3rd edition. RESULTS: The best combined motor outcome model included 3-month GMs (ß = -11.41; 95% CI = -17.34, -5.49), TEA MRI deep grey matter score (ß = -6.23; 95% CI = -9.47, -2.99) and early HNNE reflexes (ß = 3.51; 95% CI = 0.86, 6.16). Combined cognitive model included 3-month GMs (ß = -10.01; 95% CI = -15.90, -4.12) and TEA HNNE score (ß = 1.33; 95% CI = 0.57, 2.08). CONCLUSION: Early neonatal neurological assessment improves associations with motor outcomes when combined with term MRI and 3-month GMs. Term neurological assessment combined with 3-month GMs improves associations with cognitive outcomes. IMPACT: We present associations between 32- and 40-week MRI, comprehensive clinical assessments and later 2-year motor and cognitive outcomes for children born <31 weeks gestation. MRI and clinical assessment of motor, neurological and neurobehavioural function earlier than term equivalent age in very preterm infants is safe and becoming more available in clinical settings. Most of these children are discharged from hospital before term age and so completing assessments prior to discharge can assist with follow up. MRI and neurological assessment prior to term equivalent age while the child is still in hospital can provide earlier identification of children at highest risk of adverse outcomes and guide follow-up screening and intervention services.
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Cognição , Lactente Extremamente Prematuro , Imageamento por Ressonância Magnética/métodos , Atividade Motora , Feminino , Humanos , Recém-Nascido , Masculino , Estudos ProspectivosRESUMO
Very preterm-born infants are at risk of adverse neurodevelopmental outcomes. Brain magnetic resonance imaging (MRI) at term equivalent age (TEA) can probe tissue microstructure and morphology, and demonstrates potential in the early prediction of outcomes. In this study, we use the recently introduced fixel-based analysis method for diffusion MRI to investigate the association between microstructure and morphology at TEA, and motor and cognitive development at 1 and 2 years corrected age (CA). Eighty infants born <31 weeks' gestation successfully underwent diffusion MRI (3T; 64 directions; b â= â2000s/mm2) at term equivalent age, and had neurodevelopmental follow-up using the Bayley-III motor and cognitive assessments at 1 year (n â= â78) and/or 2 years (n â= â76) CA. Diffusion MRI data were processed using constrained spherical deconvolution (CSD) and aligned to a study-specific fibre orientation distribution template, yielding measures of fibre density (FD), fibre-bundle cross-section (FC), and fibre density and bundle cross-section (FDC). The association between FD, FC, and FDC at TEA, and motor and cognitive composite scores at 1 and 2 years CA, and change in composite scores from 1 to 2 years, was assessed using whole-brain fixel-based analysis. Additionally, the association between diffusion tensor imaging (DTI) metrics (fractional anisotropy FA, mean diffusivity MD, axial diffusivity AD, radial diffusivity RD) and outcomes was investigated. Motor function at 1 and 2 years CA was associated with CSD-based measures of the bilateral corticospinal tracts and corpus callosum. Cognitive function was associated with CSD-based measures of the midbody (1-year outcomes only) and splenium of the corpus callosum, as well as the bilateral corticospinal tracts. The change in motor/cognitive outcomes from 1 to 2 years was associated with CSD-based measures of the splenium of the corpus callosum. Analysis of DTI-based measures showed overall less extensive associations. Post-hoc analysis showed that associations were weaker for 2-year outcomes than they were for 1-year outcomes. Infants with better neurodevelopmental outcomes demonstrated higher FD, FC, and FDC at TEA, indicating better information transfer capacity which may be related to increased number of neurons, increased myelination, thicker bundles, and/or combinations thereof. The fibre bundles identified here may serve as the basis for future studies investigating the predictive ability of these metrics.
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Desenvolvimento Infantil/fisiologia , Cognição/fisiologia , Corpo Caloso/anatomia & histologia , Lactente Extremamente Prematuro/fisiologia , Tratos Piramidais/anatomia & histologia , Substância Branca/anatomia & histologia , Pré-Escolar , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/ultraestrutura , Imagem de Tensor de Difusão , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/ultraestrutura , Substância Branca/diagnóstico por imagem , Substância Branca/ultraestruturaRESUMO
BACKGROUND AND AIMS: Preterm birth imposes a high risk for developing neuromotor delay. Earlier prediction of adverse outcome in preterm infants is crucial for referral to earlier intervention. This study aimed to predict abnormal motor outcome at 2 years from early brain diffusion magnetic resonance imaging (MRI) acquired between 29 and 35 weeks postmenstrual age (PMA) using a deep learning convolutional neural network (CNN) model. METHODS: Seventy-seven very preterm infants (born <31 weeks gestational age (GA)) in a prospective longitudinal cohort underwent diffusion MR imaging (3T Siemens Trio; 64 directions, b â= â2000 âs/mm2). Motor outcome at 2 years corrected age (CA) was measured by Neuro-Sensory Motor Developmental Assessment (NSMDA). Scores were dichotomised into normal (functional score: 0, normal; n â= â48) and abnormal scores (functional score: 1-5, mild-profound; n â= â29). MRIs were pre-processed to reduce artefacts, upsampled to 1.25 âmm isotropic resolution and maps of fractional anisotropy (FA) were estimated. Patches extracted from each image were used as inputs to train a CNN, wherein each image patch predicted either normal or abnormal outcome. In a postprocessing step, an image was classified as predicting abnormal outcome if at least 27% (determined by a grid search to maximise the model performance) of its patches predicted abnormal outcome. Otherwise, it was considered as normal. Ten-fold cross-validation was used to estimate performance. Finally, heatmaps of model predictions for patches in abnormal scans were generated to explore the locations associated with abnormal outcome. RESULTS: For the identification of infants with abnormal motor outcome based on the FA data from early MRI, we achieved mean sensitivity 70% (standard deviation SD 19%), mean specificity 74% (SD 39%), mean AUC (area under the receiver operating characteristic curve) 72% (SD 14%), mean F1 score of 68% (SD 13%) and mean accuracy 73% (SD 19%) on an unseen test data set. Patch-based prediction heatmaps showed that the patches around the motor cortex and somatosensory regions were most frequently identified by the model with high precision (74%) as a location associated with abnormal outcome. Part of the cerebellum, and occipital and frontal lobes were also highly associated with abnormal NSMDA/motor outcome. DISCUSSION/CONCLUSION: This study established the potential of an early brain MRI-based deep learning CNN model to identify preterm infants at risk of a later motor impairment and to identify brain regions predictive of adverse outcome. Results suggest that predictions can be made from FA maps of diffusion MRIs well before term equivalent age (TEA) without any prior knowledge of which MRI features to extract and associated feature extraction steps. This method, therefore, is suitable for any case of brain condition/abnormality. Future studies should be conducted on a larger cohort to re-validate the robustness and effectiveness of these models.
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Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Aprendizado Profundo , Imagem de Difusão por Ressonância Magnética , Modelos Neurológicos , Transtornos Motores/diagnóstico por imagem , Transtornos Motores/patologia , Humanos , Lactente , Recém-Nascido Prematuro , Estudos Longitudinais , Redes Neurais de Computação , Transtornos do Neurodesenvolvimento/diagnóstico por imagem , Transtornos do Neurodesenvolvimento/patologia , Estudos ProspectivosRESUMO
AIM: To examine the diagnostic ability of early magnetic resonance imaging (MRI; <36wks postmenstrual age) to detect later adverse motor outcomes or cerebral palsy (CP) in infants born preterm. METHOD: Studies of infants born preterm with MRI earlier than 36 weeks postmenstrual age and quantitative motor data or a diagnosis of CP at or beyond 1 year corrected age were identified. Study details were extracted and meta-analyses performed where possible. Quality of included studies was evaluated with the QUADAS-2 (a revised tool for the quality assessment of diagnostic accuracy studies). RESULTS: Thirty-one articles met the inclusion criteria, five of which reported diagnostic accuracy and five reported data sufficient for calculation of diagnostic accuracy. Early structural MRI global scores detected a later diagnosis of CP with a pooled sensitivity of 100% (95% confidence interval [CI] 86-100) and a specificity of 93% (95% CI 59-100). Global structural MRI scores determined adverse motor outcomes with a pooled sensitivity of 89% (95% CI 44-100) and a specificity of 98% (95% CI 90-100). White matter scores determined adverse motor outcomes with a pooled sensitivity of 33% (95% CI 20-48) and a specificity of 83% (95% CI 78-88). INTERPRETATION: Early structural MRI has reasonable sensitivity and specificity to determine adverse motor outcomes and CP in infants born preterm. Greater reporting of diagnostic accuracy in studies examining relationships with motor outcomes and CP is required to facilitate clinical utility of early MRI. WHAT THIS PAPER ADDS: Early magnetic resonance imaging (MRI) has reasonable sensitivity and specificity to determine later adverse motor outcomes and cerebral palsy (CP). Detection of infants who progressed to CP was stronger than motor outcomes. Global MRI scores determined adverse motor outcomes more accurately than white matter scores. Few studies report diagnostic accuracy of early MRI findings. Diagnostic accuracy is required to draw clinically meaningful conclusions from early MRI studies.
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Paralisia Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética , Transtornos dos Movimentos/diagnóstico por imagem , Animais , Diagnóstico Precoce , Humanos , Lactente , Recém-Nascido PrematuroRESUMO
BACKGROUND: More than 50 percent of all infants born very preterm will experience significant motor and cognitive impairment. Provision of early intervention is dependent upon accurate, early identification of infants at risk of adverse outcomes. Magnetic resonance imaging at term equivalent age combined with General Movements assessment at 12 weeks corrected age is currently the most accurate method for early prediction of cerebral palsy at 12 months corrected age. To date no studies have compared the use of earlier magnetic resonance imaging combined with neuromotor and neurobehavioural assessments (at 30 weeks postmenstrual age) to predict later motor and neurodevelopmental outcomes including cerebral palsy (at 12-24 months corrected age). This study aims to investigate i) the relationship between earlier brain imaging and neuromotor/neurobehavioural assessments at 30 and 40 weeks postmenstrual age, and ii) their ability to predict motor and neurodevelopmental outcomes at 3 and 12 months corrected age. METHODS/DESIGN: This prospective cohort study will recruit 80 preterm infants born ≤ 30 week's gestation and a reference group of 20 healthy term born infants from the Royal Brisbane & Women's Hospital in Brisbane, Australia. Infants will undergo brain magnetic resonance imaging at approximately 30 and 40 weeks postmenstrual age to develop our understanding of very early brain structure at 30 weeks and maturation that occurs between 30 and 40 weeks postmenstrual age. A combination of neurological (Hammersmith Neonatal Neurologic Examination), neuromotor (General Movements, Test of Infant Motor Performance), neurobehavioural (NICU Network Neurobehavioural Scale, Premie-Neuro) and visual assessments will be performed at 30 and 40 weeks postmenstrual age to improve our understanding of the relationship between brain structure and function. These data will be compared to motor assessments at 12 weeks corrected age and motor and neurodevelopmental outcomes at 12 months corrected age (neurological assessment by paediatrician, Bayley scales of Infant and Toddler Development, Alberta Infant Motor Scale, Neurosensory Motor Developmental Assessment) to differentiate atypical development (including cerebral palsy and/or motor delay). DISCUSSION: Earlier identification of those very preterm infants at risk of adverse neurodevelopmental and motor outcomes provides an additional period for intervention to optimise outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000280707. Registered 8 March 2013.
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Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Recém-Nascido Prematuro/fisiologia , Encéfalo/fisiopatologia , Paralisia Cerebral/diagnóstico , Deficiências do Desenvolvimento/diagnóstico , Eletroencefalografia , Idade Gestacional , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Exame Neurológico , Estudos Prospectivos , Medição de RiscoRESUMO
BACKGROUND: Very preterm infants are at increased risk of neurodevelopmental impairments. The Neonatal Visual Assessment (NVA) assesses visual function and outcomes and has been used to assess early neurodevelopmental outcomes. This study aimed to compare NVA results of very preterm and term-born infants and to calculate the sensitivity and specificity of the NVA at term equivalent age (TEA) and three months corrected age (CA) to predict motor and cognitive outcomes at 12 months CA in very preterm infants. METHODS: This prospective observational cohort study recruited infants born before 31 weeks gestation and a healthy term-born control group. The NVA was assessed at TEA and three months CA, and neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development, Third Edition; Neurosensory Motor Developmental Assessment; Alberta Infant Motor Scale) were performed at 12 months CA. The sensitivity and specificity of the NVA to predict outcomes were calculated based on a previously published optimality score. RESULTS: 248 preterm (54 % male) and 46 term-born infants (48 % male) were analysed. The mean NVA scores of preterm and term-born infants were significantly different at TEA (preterm 3.1±2.1; term-born 1.2±1.7, p < 0.001). The NVA had moderate sensitivity (59-78 %) and low specificity (25-27 %) at TEA, and low sensitivity (21-28 %) and high specificity (86-87 %) at three months CA for the prediction of preterm infants' outcomes at 12 months CA. CONCLUSION: The NVA at TEA and three months CA was not a strong predictor of motor and cognitive impairments in this contemporary cohort of very preterm infants.
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Desenvolvimento Infantil , Humanos , Masculino , Feminino , Recém-Nascido , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Lactente Extremamente Prematuro/fisiologia , Sensibilidade e Especificidade , Cognição , Recém-Nascido Prematuro/crescimento & desenvolvimento , Recém-Nascido Prematuro/fisiologia , Estudos Prospectivos , LactenteRESUMO
The Motor Optimality Score, revised (MOS-R) is an extension of the Prechtl General Movements Assessment. This study aims to determine the relationship between MOS-R and 2-year neurodevelopmental outcomes in a cohort of 169 infants born very preterm (<31 weeks' gestational age), and to examine the predictive validity of the MOS-R at 3−4 months' corrected age (CA) above perinatal variables associated with poor outcomes, including Prechtl fidgety movements. Development at 2 years' CA was assessed using Bayley Scales of Infant and Toddler Development, Third edition (Bayley-III) (motor/cognitive impairment: Bayley-III ≤ 85) and Neurological, Sensory, Motor, Developmental Assessment (NSMDA) (neurosensory motor impairment: NSMDA ≥ 12). Cerebral palsy (CP) was classified at 2 years as definite or clinical. The MOS-R was related to 2-year outcomes: Bayley-III motor (BMOS-R = 1.24 95% confidence interval (0.78, 1.70)), cognitive (BMOS-R = 0.91 (0.48, 1.35)), NSMDA scores (BMOS-R = −0.34 (−0.42, −0.25)), definite CP (odds ratio [OR] 0.67 (0.53, 0.86)), clinical CP (OR 0.74 (0.66, 0.83)) for each 1-point increase in MOS-R. MOS-R ≤ 23 predicted motor (sensitivity 78% (60−91%); specificity 63% (54−72%)) and neurosensory motor impairment (sensitivity 86% (64−97%); specificity 59% (51−68%)). The MOS-R is strongly related to CP and motor and cognitive delay at 2 years and is a good predictor of motor and neurosensory motor impairment.
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INTRODUCTION: Infants born very preterm are at risk of adverse neurodevelopmental outcomes, including cognitive deficits, motor impairments and cerebral palsy. Earlier identification enables targeted early interventions to be implemented with the aim of improving outcomes. METHODS AND ANALYSIS: Protocol for 6-year follow-up of two cohorts of infants born <31 weeks gestational age (PPREMO: Prediction of Preterm Motor Outcomes; PREBO: Prediction of Preterm Brain Outcomes) and a small term-born reference sample in Brisbane, Australia. Both preterm cohorts underwent very early MRI and concurrent clinical assessment at 32 and 40 weeks postmenstrual age (PMA) and were followed up at 3, 12 and 24 months corrected age (CA). This study will perform MRI and electroencephalography (EEG). Primary outcomes include the Movement Assessment Battery for Children second edition and Full-Scale IQ score from the Wechsler Intelligence Scale for Children fifth edition (WISC-V). Secondary outcomes include the Gross Motor Function Classification System for children with cerebral palsy; executive function (Behavior Rating Inventory of Executive Function second edition, WISC-V Digit Span and Picture Span, Wisconsin Card Sorting Test 64 Card Version); attention (Test of Everyday Attention for Children second edition); language (Clinical Evaluation of Language Fundamentals fifth edition), academic achievement (Woodcock Johnson IV Tests of Achievement); mental health and quality of life (Development and Well-Being Assessment, Autism Spectrum Quotient-10 Items Child version and Child Health Utility-9D). AIMS: Examine the ability of early neonatal MRI, EEG and concurrent clinical measures at 32 weeks PMA to predict motor, cognitive, language, academic achievement and mental health outcomes at 6 years CA.Determine if early brain abnormalities persist and are evident on brain MRI at 6 years CA and the relationship to EEG and concurrent motor, cognitive, language, academic achievement and mental health outcomes. ETHICS AND DISSEMINATION: Ethical approval has been obtained from Human Research Ethics Committees at Children's Health Queensland (HREC/19/QCHQ/49800) and The University of Queensland (2019000426). Study findings will be presented at national and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12619000155190p. WEB ADDRESS OF TRIAL: http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12619000155190p.
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Encéfalo/diagnóstico por imagem , Intervenção Médica Precoce/métodos , Imageamento por Ressonância Magnética/métodos , Transtornos do Neurodesenvolvimento/complicações , Nascimento Prematuro/epidemiologia , Sucesso Acadêmico , Austrália/epidemiologia , Biomarcadores/metabolismo , Encéfalo/fisiopatologia , Paralisia Cerebral/diagnóstico , Paralisia Cerebral/epidemiologia , Paralisia Cerebral/fisiopatologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/fisiopatologia , Eletroencefalografia/métodos , Feminino , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Idioma , Masculino , Saúde Mental/estatística & dados numéricos , Doença dos Neurônios Motores/diagnóstico , Doença dos Neurônios Motores/epidemiologia , Doença dos Neurônios Motores/fisiopatologia , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/epidemiologia , Estudos Prospectivos , Qualidade de VidaRESUMO
Preterm birth causes significant disruption in ongoing brain development, frequently resulting in adverse neurodevelopmental outcomes. Brain imaging using diffusion MRI may provide valuable insight into microstructural properties of the developing brain. The aim of this study was to establish whether the recently introduced fixel-based analysis method, with its associated measures of fibre density (FD), fibre bundle cross-section (FC), and fibre density and bundle cross-section (FDC), is suitable for the investigation of the preterm infant brain at term equivalent age. High-angular resolution diffusion weighted images (HARDI) of 55 preterm-born infants and 20 term-born infants, scanned around term-equivalent age, were included in this study (3â¯T, 64 directions, bâ¯=â¯2000â¯s/mm2). Postmenstrual age at the time of MRI, and intracranial volume (FC and FDC only), were identified as confounding variables. Gestational age at birth was correlated with all fixel measures in the splenium of the corpus callosum. Compared to term-born infants, preterm infants showed reduced FD, FC, and FDC in a number of regions, including the corpus callosum, anterior commissure, cortico-spinal tract, optic radiations, and cingulum. Preterm infants with minimal macroscopic brain abnormality showed more extensive reductions than preterm infants without any macroscopic brain abnormality; however, little differences were observed between preterm infants with no and with minimal brain abnormality. FC showed significant reductions in preterm versus term infants outside regions identified with FD and FDC, highlighting the complementary role of these measures. Fixel-based analysis identified both microstructural and macrostructural abnormalities in preterm born infants, providing a more complete picture of early brain development than previous diffusion tensor imaging (DTI) based approaches.
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Encéfalo/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Mapeamento Encefálico , Imagem de Difusão por Ressonância Magnética , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Imageamento por Ressonância Magnética , MasculinoRESUMO
AIM: This study aimed to examine associations between structural MRI and concurrent motor, neurological and neurobehavioral measures at 30-32â¯weeks postmenstrual age (PMA; 'Early'), and at term equivalent age ('Term'). METHOD: In this prospective cohort study, infants underwent Early MRI (nâ¯=â¯119; 73 male; median 32â¯weeks 1â¯day PMA) and Term MRI (nâ¯=â¯102; 61 male; median 40â¯weeks 4â¯days PMA) at 3â¯T. Structural images were scored generating white matter (WM), cortical gray matter, deep gray matter, cerebellar and global brain abnormality scores. Clinical measures were General Movements Assessment (GMs), Hammersmith Neonatal Neurological Examination (HNNE) and NICU Neonatal Neurobehavioral Scale (NNNS). The Premie-Neuro was administered Early and the Test of Infant Motor Performance (TIMP) and a visual assessment at Term. RESULTS: Early MRI cerebellar scores were strongly associated with neurological components of HNNE (reflexes), NNNS (Hypertonicity), the Premie-Neuro neurological subscale (regression coefficient ßâ¯=â¯-0.06; 95% confidence interval CIâ¯=â¯-0.09, -0.04; pâ¯<â¯.001) and cramped-synchronized GMs (ßâ¯=â¯1.10; 95%CIâ¯=â¯0.57, 1.63; pâ¯<â¯.001). Term MRI WM and global scores were strongly associated with the TIMP (WM ßâ¯=â¯-1.02; 95%CIâ¯=â¯-1.67, -0.36; pâ¯=â¯.002; global ßâ¯=â¯-1.59; 95%CIâ¯=â¯-2.62, -0.56; pâ¯=â¯.001). INTERPRETATION: Brain structure on Early and Term MRI was associated with concurrent motor, neurological and neurobehavioral function in very preterm infants.