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      Cerebral Oxygenation and Autoregulation in Very Preterm Infants Developing IVH During the Transitional Period: A Pilot Study

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          Abstract

          Background: The transitional period, defined as the first 72 h after preterm birth, is often characterized by a significant hemodynamic instability, which represents an important risk factor for such neurological complications of prematurity as intraventricular hemorrhage (IVH). The impairment of cerebral autoregulation plays a key role in the pathogenesis of IVH, whose incidence is highest during the transitional period. This pilot study aimed to evaluate whether patterns of cerebral autoregulation and oxygenation differ in relation to IVH development in very preterm infants during the transitional period.

          Methods: Infants <32 weeks' gestation were enrolled within 12 h from birth. A simultaneous monitoring of cerebral oxygenation (CrSO 2) by near-infrared spectroscopy and of heart rate and peripheral oxygen saturation by pulse oximetry was performed over the first 72 h. Cerebral fractional oxygen extraction (cFTOE) and tissue oxygenation-heart rate reactivity index (TOHRx), which represents a marker of cerebrovascular reactivity, were calculated. Daily cranial and cardiac ultrasound scans were performed, in order to assess the hemodynamic status and to detect a possible IVH onset. CrSO 2 and cFTOE, clustered on 6-hour epochs, were compared between infants who developed IVH during the study period and those who did not. A between-group comparison of TOHRx before and after IVH detection was also performed.

          Results: Twenty preterm infants with a median gestational age of 27 weeks (interquartile range, IQR: 25-30 weeks) and median birth weight of 895 g (IQR: 822-1208 g) were enrolled. Of these, 8 developed IVH. The median age at IVH detection was 40 h (IQR: 30-48 h). Pre-IVH TOHRx was significantly higher compared to matched control periods ( p <0.001). CrSO 2 was significantly lower from 12 to 30 h and from 42 h onwards in cases compared to controls; however, a temporary CrSO 2 rise preceded IVH detection. Similarly, cFTOE was significantly higher in IVH infants from 12 to 30 h and from 48 to 72 h, with a transient decrease between the two periods.

          Conclusions: In preterm infants during the transitional period, the development of IVH is preceded by transient changes in cerebral oxygenation and oxygen extraction which, in turn, may underlie an early impairment of cerebral autoregulation. Larger studies are needed to confirm these preliminary findings.

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          Most cited references27

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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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            Periventricular/Intraventricular Hemorrhage and Neurodevelopmental Outcomes: A Meta-analysis.

            Periventricular/intraventricular hemorrhage (PIVH) is a common short-term morbidity in preterm infants, but its long-term neurodevelopmental impact, particularly with mild PIVH, remains unclear.
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              Cerebral oxygenation, extraction, and autoregulation in very preterm infants who develop peri-intraventricular hemorrhage.

              To test the hypothesis that near-infrared spectroscopy (NIRS)-determined patterns of regional cerebral oxygen saturation (rScO2), cerebral fractional tissue oxygen extraction (cFTOE), and autoregulatory ability can identify neonates at risk for developing peri-intraventricular hemorrhage (PIVH).
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                Author and article information

                Contributors
                Journal
                Front Pediatr
                Front Pediatr
                Front. Pediatr.
                Frontiers in Pediatrics
                Frontiers Media S.A.
                2296-2360
                15 July 2020
                2020
                : 8
                : 381
                Affiliations
                [1] 1Neonatal Intensive Care Unit, S. Orsola-Malpighi University Hospital , Bologna, Italy
                [2] 2Department of Medical and Surgical Sciences (DIMEC), University of Bologna , Bologna, Italy
                Author notes

                Edited by: Jonathan P. Mintzer, Hackensack University Medical Center Mountainside, United States

                Reviewed by: Shahab Noori, Keck School of Medicine, University of Southern California, United States; Anup C. Katheria, Sharp Mary Birch Hospital for Women & Newborns, United States; Christopher J. Rhee, Texas Children's Hospital, United States

                *Correspondence: Silvia Martini silvia.martini9@ 123456unibo.it

                This article was submitted to Neonatology, a section of the journal Frontiers in Pediatrics

                Article
                10.3389/fped.2020.00381
                7373744
                3fe966e0-85c5-4d2c-84d2-21f6bbf24b1e
                Copyright © 2020 Cimatti, Martini, Galletti, Vitali, Aceti, Frabboni, Faldella and Corvaglia.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 April 2020
                : 04 June 2020
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 30, Pages: 8, Words: 5297
                Categories
                Pediatrics
                Original Research

                ivh,nirs,cerebral oxygenation,cerebral autoregulation,transitional period,echocardiography,preterm infants

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