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      Post hemorrhagic hydrocephalus and neurodevelopmental outcomes in a context of neonatal intraventricular hemorrhage: an institutional experience in 122 preterm children

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          Abstract

          Background

          Intraventricular hemorrhage (IVH) is a frequent complication in extreme and very preterm births. Despite a high risk of death and impaired neurodevelopment, the precise prognosis of infants with IVH remains unclear. The objective of this study was to evaluate the rate and predictive factors of evolution to post hemorrhagic hydrocephalus (PHH) requiring a shunt, in newborns with IVH and to report their neurodevelopmental outcomes at 2 years of age.

          Methods

          Among all preterm newborns admitted to the department of neonatalogy at Rouen University Hospital, France between January 2000 and December 2013, 122 had an IVH and were included in the study. Newborns with grade 1 IVH according to the Papile classification were excluded.

          Results

          At 2-year, 18% ( n = 22) of our IVH cohort required permanent cerebro spinal fluid (CSF) derivation. High IVH grade, low gestational age at birth and increased head circumference were risk factors for PHH. The rate of death of IVH was 36.9% ( n = 45). The rate of cerebral palsy was 55.9% ( n = 43) in the 77 surviving patients (49.4%). Risk factors for impaired neurodevelopment were high grade IVH and increased head circumference.

          Conclusion

          High IVH grade was strongly correlated with death and neurodevelopmental outcome. The impact of an increased head circumference highlights the need for early management. CSF biomarkers and new medical treatments such as antenatal magnesium sulfate have emerged and could predict and improve the prognosis of these newborns with PHH.

          Electronic supplementary material

          The online version of this article (10.1186/s12887-018-1249-x) contains supplementary material, which is available to authorized users.

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          Most cited references22

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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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            Neurodevelopmental outcome at 2 years for preterm children born at 22 to 34 weeks’ gestation in France in 2011: EPIPAGE-2 cohort study

            Objectives To describe neurodevelopmental outcomes at 2 years corrected age for children born alive at 22-26, 27-31, and 32-34 weeks’ gestation in 2011, and to evaluate changes since 1997. Design Population based cohort studies, EPIPAGE and EPIPAGE-2. Setting France. Participants 5567 neonates born alive in 2011 at 22-34 completed weeks’ gestation, with 4199 survivors at 2 years corrected age included in follow-up. Comparison of outcomes reported for 3334 (1997) and 2418 (2011) neonates born alive in the nine regions participating in both studies. Main outcome measures Survival; cerebral palsy (2000 European consensus definition); scores below threshold on the neurodevelopmental Ages and Stages Questionnaire (ASQ; at least one of five domains below threshold) if completed between 22 and 26 months corrected age, in children without cerebral palsy, blindness, or deafness; and survival without severe or moderate neuromotor or sensory disabilities (cerebral palsy with Gross Motor Function Classification System levels 2-5, unilateral or bilateral blindness or deafness). Results are given as percentage of outcome measures with 95% confidence intervals. Results Among 5170 liveborn neonates with parental consent, survival at 2 years corrected age was 51.7% (95% confidence interval 48.6% to 54.7%) at 22-26 weeks’ gestation, 93.1% (92.1% to 94.0%) at 27-31 weeks’ gestation, and 98.6% (97.8% to 99.2%) at 32-34 weeks’ gestation. Only one infant born at 22-23 weeks survived. Data on cerebral palsy were available for 3599 infants (81.0% of the eligible population). The overall rate of cerebral palsy at 24-26, 27-31, and 32-34 weeks’ gestation was 6.9% (4.7% to 9.6%), 4.3% (3.5% to 5.2%), and 1.0% (0.5% to 1.9%), respectively. Responses to the ASQ were analysed for 2506 children (56.4% of the eligible population). The proportion of children with an ASQ result below threshold at 24-26, 27-31, and 32-34 weeks’ gestation were 50.2% (44.5% to 55.8%), 40.7% (38.3% to 43.2%), and 36.2% (32.4% to 40.1%), respectively. Survival without severe or moderate neuromotor or sensory disabilities among live births increased between 1997 and 2011, from 45.5% (39.2% to 51.8%) to 62.3% (57.1% to 67.5%) at 25-26 weeks’ gestation, but no change was observed at 22-24 weeks’ gestation. At 32-34 weeks’ gestation, there was a non-statistically significant increase in survival without severe or moderate neuromotor or sensory disabilities (P=0.61), but the proportion of survivors with cerebral palsy declined (P=0.01). Conclusions In this large cohort of preterm infants, rates of survival and survival without severe or moderate neuromotor or sensory disabilities have increased during the past two decades, but these children remain at high risk of developmental delay.
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              Mechanisms of hydrocephalus after neonatal and adult intraventricular hemorrhage.

              Intraventricular hemorrhage (IVH) is a cause of significant morbidity and mortality and is an independent predictor of a worse outcome in intracerebral hemorrhage (ICH) and germinal matrix hemorrhage (GMH). IVH may result in both injuries to the brain as well as hydrocephalus. This paper reviews evidence on the mechanisms and potential treatments for IVH-induced hydrocephalus. One frequently cited theory to explain hydrocephalus after IVH involves obliteration of the arachnoid villi by microthrombi with subsequent inflammation and fibrosis causing CSF outflow obstruction. Although there is some evidence to support this theory, there may be other mechanisms involved, which contribute to the development of hydrocephalus. It is also unclear whether the causes of acute and chronic hydrocephalus after hemorrhage occur via different mechanisms; mechanical obstruction by blood in the former, and inflammation and fibrosis in the latter. Management of IVH and strategies for prevention of brain injury and hydrocephalus are areas requiring further study. A better understanding of the pathogenesis of hydrocephalus after IVH, may lead to improved strategies to prevent and treat post-hemorrhagic hydrocephalus.
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                Author and article information

                Contributors
                +33 232 888 177 , vianney.gilard@chu-rouen.fr
                alexandra.chadie@chu-rouen.fr
                ferraccifx@free.fr
                Marie.Brasseur-Daudruy@chu-rouen.fr
                francois.proust@neurochirurgie.fr
                stephane.marret@chu-rouen.fr
                sophie.curey@chu-rouen.fr
                Journal
                BMC Pediatr
                BMC Pediatr
                BMC Pediatrics
                BioMed Central (London )
                1471-2431
                31 August 2018
                31 August 2018
                2018
                : 18
                : 288
                Affiliations
                [1 ]GRID grid.41724.34, Neurosurgery Department, , Rouen University Hospital, ; 1 rue de Germont, 76000 Rouen, France
                [2 ]GRID grid.41724.34, Paediatrics Department, , Rouen University Hospital, ; 76000 Rouen, France
                [3 ]GRID grid.41724.34, Department of Radiology, , Rouen University Hospital, ; 76000 Rouen, France
                [4 ]ISNI 0000 0001 2177 138X, GRID grid.412220.7, Neurosurgery Department, , Strasbourg University Hospital, ; 67000 Strasbourg, France
                Author information
                http://orcid.org/0000-0001-6040-665X
                Article
                1249
                10.1186/s12887-018-1249-x
                6119335
                30170570
                fa20561b-a821-4d2b-ba0d-9e39e08228f1
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 11 June 2018
                : 8 August 2018
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Pediatrics
                intraventricular hemorrhage,neonatal,hydrocephalus,neurodevelopmental outcomes
                Pediatrics
                intraventricular hemorrhage, neonatal, hydrocephalus, neurodevelopmental outcomes

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