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      Prediction of intraventricular haemorrhage in preterm infants using time series analysis of blood pressure and respiratory signals

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          Abstract

          Despite the decline in mortality rates of extremely preterm infants, intraventricular haemorrhage (IVH) remains common in survivors. The need for resuscitation and cardiorespiratory management, particularly within the first 24 hours of life, are important factors in the incidence and timing of IVH. Variability analyses of heart rate and blood pressure data has demonstrated potential approaches to predictive monitoring. In this study, we investigated the early identification of infants at a high risk of developing IVH, using time series analysis of blood pressure and respiratory data. We also explore approaches to improving model performance, such as the inclusion of multiple variables and signal pre-processing to enhance the results from detrended fluctuation analysis. Of the models we evaluated, the highest area under receiver-operator characteristic curve (5th, 95th percentile) achieved was 0.921 (0.82, 1.00) by mean diastolic blood pressure and the long-term scaling exponent of pulse interval (PI α 2), exhibiting a sensitivity of >90% at a specificity of 75%. Following evaluation in a larger population, our approach may be useful in predictive monitoring to identify infants at high risk of developing IVH, offering caregivers more time to adjust intensive care treatment.

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          Most cited references 21

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          Intraventricular hemorrhage in premature infants: mechanism of disease.

          Intraventricular hemorrhage (IVH) is a major complication of prematurity. IVH typically initiates in the germinal matrix, which is a richly vascularized collection of neuronal-glial precursor cells in the developing brain. The etiology of IVH is multifactorial and is primarily attributed to the intrinsic fragility of the germinal matrix vasculature and the disturbance in the cerebral blood flow (CBF). Although this review broadly describes the pathogenesis of IVH, the main focus is on the recent development in molecular mechanisms that elucidates the fragility of the germinal matrix vasculature. The microvasculature of the germinal matrix is frail because of an abundance of angiogenic blood vessels that exhibit paucity of pericytes, immaturity of basal lamina, and deficiency of glial fibrillary acidic protein (GFAP) in the ensheathing astrocytes endfeet. High VEGF and angiopoietin-2 levels activate a rapid angiogenesis in the germinal matrix. The elevation of these growth factors may be ascribed to a relative hypoxia of the germinal matrix perhaps resulting from high metabolic activity and oxygen consumption of the neural progenitor cells. Hence, the rapid stabilization of the angiogenic vessels and the restoration of normal CBF on the first day of life are potential strategies to prevent IVH in premature infants.
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            Fluctuating cerebral blood-flow velocity in respiratory-distress syndrome. Relation to the development of intraventricular hemorrhage.

            We studied whether changes in cerebral blood-flow velocity occur during the respiratory-distress syndrome and whether, if present, they are related to the subsequent occurrence of intraventricular hemorrhage. Fifty infants weighing less than 1500 g at birth who required mechanical ventilation for the respiratory-distress syndrome were studied from the first hours of life. Blood-flow velocity in the anterior cerebral artery was measured at the anterior fontanel by means of the Doppler technique. At 12 hours of age, the infants had blood-flow velocity patterns that were either stable or fluctuating and that reflected the patterns of simultaneously recorded blood pressure. Intraventricular hemorrhage subsequently developed in 21 of 23 infants with the fluctuating pattern (in most of them, within the next 24 hours), but in only 7 of 27 infants with the stable pattern. Preliminary data suggest that the cerebral hemodynamic fluctuations are related to the respiratory disease and particularly to the mechanics of respiration. We conclude that the fluctuating pattern of cerebral blood-flow velocity in infants with the respiratory-distress syndrome indicates an extreme risk of the development of intraventricular hemorrhage and may represent a major and potentially preventable etiologic factor.
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              Elevated cerebral pressure passivity is associated with prematurity-related intracranial hemorrhage.

              Cerebral pressure passivity is common in sick premature infants and may predispose to germinal matrix/intraventricular hemorrhage (GM/IVH), a lesion with potentially serious consequences. We studied the association between the magnitude of cerebral pressure passivity and GM/IVH. We enrolled infants <32 weeks' gestational age with indwelling mean arterial pressure (MAP) monitoring and excluded infants with known congenital syndromes or antenatal brain injury. We recorded continuous MAP and cerebral near-infrared spectroscopy hemoglobin difference (HbD) signals at 2 Hz for up to 12 hours/day and up to 5 days. Coherence and transfer function analysis between MAP and HbD signals was performed in 3 frequency bands (0.05-0.25, 0.25-0.5, and 0.5-1.0 Hz). Using MAP-HbD gain and clinical variables (including chorioamnionitis, Apgar scores, gestational age, birth weight, neonatal sepsis, and Score for Neonatal Acute Physiology II), we built a logistic regression model that best predicts cranial ultrasound abnormalities. In 88 infants (median gestational age: 26 weeks [range 23-30 weeks]), early cranial ultrasound showed GM/IVH in 31 (37%) and parenchymal echodensities in 10 (12%) infants; late cranial ultrasound showed parenchymal abnormalities in 19 (30%) infants. Low-frequency MAP-HbD gain (highest quartile mean) was significantly associated with early GM/IVH but not other ultrasound findings. The most parsimonious model associated with early GM/IVH included only gestational age and MAP-HbD gain. This novel cerebrovascular monitoring technique allows quantification of cerebral pressure passivity as MAP-HbD gain in premature infants. High MAP-HbD gain is significantly associated with GM/IVH. Precise temporal and causal relationship between MAP-HbD gain and GM/IVH awaits further study.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                24 April 2017
                2017
                : 7
                Affiliations
                [1 ]School of Electrical and Information Engineering, University of Sydney , Sydney, Australia
                [2 ]Woolcock Institute of Medical Research, University of Sydney , Sydney, Australia
                [3 ]Westmead Hospital , Sydney, Australia
                [4 ]School of Paediatrics and Child Health, University of Sydney , Sydney, Australia
                Author notes
                Article
                srep46538
                10.1038/srep46538
                5402275
                28436467
                Copyright © 2017, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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