Intraventricular Hemorrhage and Developmental Outcomes at 24 Months of Age in Extremely Preterm Infants

O’Shea, T. Michael; Allred, Elizabeth N.; Kuban, Karl; Hirtz, Deborah; Specter, Barbara; Durfee, Sara M.; Paneth, Nigel; Leviton, Alan

doi:10.1177/0883073811424462

Cited by 100 publications

(85 citation statements)

References 30 publications

(51 reference statements)

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“…A previous study investigating IVH and developmental outcomes showed that extremely preterm infants with IVH and white matter lesions did not have increased risk of neurodevelopmental impairment than those with white matter lesions alone [25]. This study demonstrated that cPVL infants with low-grade and high-grade IVH both had worse neurodevelopmental outcomes than infants with isolated cPVL, and the rates of CP and developmental delay elevated as IVH grading increased.…”

Section: Discussionmentioning

confidence: 50%

Isolated Cystic Periventricular Leukomalacia Differs from Cystic Periventricular Leukomalacia with Intraventricular Hemorrhage in Prevalence, Risk Factors and Outcomes in Preterm Infants

Wang

Lin²,

Tu³

et al. 2016

Neonatology

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Background: Cystic periventricular leukomalacia (cPVL) is the most severe white matter injury and is often associated with intraventricular hemorrhage (IVH) in preterm infants. Objective: The aim of this study was to investigate the prevalence, risk factors and neurodevelopmental outcomes of isolated cPVL and cPVL with low-grade and high-grade IVH in premature infants. Methods: From 2001 to 2012, 9,964 infants with <31 weeks' gestational age (GA) admitted to Taiwan hospitals were enrolled. cPVL was classified into three groups: isolated cPVL, cPVL with low-grade (I/II) IVH, and cPVL with high-grade (III) IVH. Results: Of 7,805 infants with complete ultrasound data, 286 (3.7%) had cPVL. Among the cPVL infants, 93 (32.5%) were isolated, 118 (41.3%) had low-grade IVH and 75 (26.2%) had high-grade IVH. The risk of cPVL with IVH was significantly higher among infants with <27 weeks' GA than those with ≥27 weeks' GA, in contrast to that of isolated cPVL. Using infants without cPVL and IVH as the reference group, the most significant predictor of isolated cPVL was neonatal sepsis (odds ratio 2.39; 95% confidence interval 1.52-3.77), while 5-min Apgar score <5 (2.50; 1.48-4.21) and prolonged mechanical ventilation (2.19; 1.42-3.42) were associated with cPVL with low-grade IVH, and GA <27 weeks (2.63; 1.56-4.42), pneumothorax (3.04; 1.40-6.65) and prolonged mechanical ventilation (3.36; 1.88-6.01) contributed to cPVL with high-grade IVH. cPVL infants with low-grade and high-grade IVH had a higher risk of abnormal neurodevelopmental outcomes than infants with isolated cPVL at the age of 24 months. Conclusions: Isolated cPVL, cPVL with low-grade IVH and cPVL with high-grade IVH had different risk factors and neurodevelopmental outcomes, suggestive of different causal pathways.

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Section: Discussionmentioning

confidence: 50%

Isolated Cystic Periventricular Leukomalacia Differs from Cystic Periventricular Leukomalacia with Intraventricular Hemorrhage in Prevalence, Risk Factors and Outcomes in Preterm Infants

Wang

Lin²,

Tu³

et al. 2016

Neonatology

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“…One of the most consistent predictors of neurodevelopmental impairment in preterm infants is intraventricular hemorrhage (IVH) [1,2,3], which is recognized in the first few days of life (DOL) by cranial ultrasound, the standard imaging tool for the diagnosis of cerebral lesions in preterm infants and graded according to the classification of Papile et al [4]. …”

Section: Introductionmentioning

confidence: 99%

Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants (EpoRepair)

et al. 2015

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Background: Preterm infants suffering from intraventricular hemorrhage (IVH) are at increased risk for neurodevelopmental impairment. Observational data suggest that recombinant human erythropoietin (rEPO) improves long-term cognitive outcome in infants with IVH. Recent studies revealed a beneficial effect of early high-dose rEPO on white matter development in preterm infants determined by magnetic resonance imaging (MRI). Objectives: To summarize the current evidence and to delineate the study protocol of the EpoRepair trial (Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants). Methods: The study involves a review of the literature and the design of a double-blind, placebo-controlled, multicenter trial of repetitive high-dose rEPO administration, enrolling 120 very preterm infants with moderate-to-severe IVH diagnosed by cranial ultrasound in the first days of life, qualitative and quantitative MRI at term-equivalent age and long-term neurodevelopmental follow-up until 5 years of age. Results and Conclusions: The hypothesis generated by observational data that rEPO may improve long-term cognitive outcomes of preterm infants suffering from IVH are to be confirmed or refuted by the randomized controlled trial, EpoRepair.

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“…There is widespread agreement that the outcome following high-grade haemorrhage is poor [40] , and this is likely due in part to the destructive impact on the parenchyma [23] . However, the outcome following moderate/low-grade haemorrhage is more variable, with contradictory reports in the literature [41][42][43] . More advanced neuroimaging techniques have revealed that, even if development appears outwardly normal, functional MRI imaging following premature birth shows markedly abnormal connectivity and synchronisation [44,45] and volumetric analysis indicates a reduced brain size and cortical gyration [46][47][48][49] .…”

Section: Discussionmentioning

confidence: 99%

Moderate-Grade Germinal Matrix Haemorrhage Activates Cell Division in the Neonatal Mouse Subventricular Zone

et al. 2016

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Precise temporal and spatial control of the neural stem/progenitor cells within the subventricular zone (SVZ) germinal matrix of the brain is important for normal development in the third trimester and the early postnatal period. The high metabolic demands of proliferating germinal matrix precursors, coupled with the flimsy structure of the germinal matrix cerebral vasculature, are thought to account for the high rates of haemorrhage in extremely- and very-low-birth-weight preterm infants. Germinal matrix haemorrhage can commonly extend to intraventricular haemorrhage (IVH). Because neural stem/progenitor cells are sensitive to microenvironmental cues from the ventricular, intermediate, and basal domains within the germinal matrix, haemorrhage has been postulated to impact neurological outcomes through aberration of normal neural stem/progenitor cell behaviour. We developed an animal model of neonatal germinal matrix haemorrhage using stereotactic injection of autologous blood into the mouse neonatal germinal matrix. Pathological analysis at 4 days postinjury showed high rates of intraventricular extension and ventricular dilatation but low rates of parenchymal disruption outside the germinal zone, recapitulating key features of human “Papile grade III” IVH. At 4 days postinjury we observed proliferation in the wall of the lateral ventricle with significantly increased numbers of transient amplifying cells within the SVZ and the corpus callosum. Analysis at 21 days postinjury revealed that cortical development was also affected, with increased neuronal and concomitant reduced oligodendroglial differentiation. At the molecular level, we showed downregulation of the expression of the transmembrane receptor Notch2 in CD133^+ve cells of the SVZ, raising the possibility that the burst of precocious proliferation seen in our experimental mouse model and the skewed differentiation could be mediated by downregulation of the Notch pathway within the proximal/ventricular domain. These findings raise the possibility that Notch regulation plays a critical role in mediating the response of the neonatal SVZ to ischaemic and haemorrhagic insults.

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Intraventricular Hemorrhage and Developmental Outcomes at 24 Months of Age in Extremely Preterm Infants

Cited by 100 publications

References 30 publications

Isolated Cystic Periventricular Leukomalacia Differs from Cystic Periventricular Leukomalacia with Intraventricular Hemorrhage in Prevalence, Risk Factors and Outcomes in Preterm Infants

Isolated Cystic Periventricular Leukomalacia Differs from Cystic Periventricular Leukomalacia with Intraventricular Hemorrhage in Prevalence, Risk Factors and Outcomes in Preterm Infants

Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants (EpoRepair)

Moderate-Grade Germinal Matrix Haemorrhage Activates Cell Division in the Neonatal Mouse Subventricular Zone

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