Dataset Information

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

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.

SUBMITTER: Gilard V

PROVIDER: S-EPMC6119335 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Gilard Vianney V Chadie Alexandra A Ferracci François-Xavier FX Brasseur-Daudruy Marie M Proust François F Marret Stéphane S Curey Sophie S

BMC pediatrics 20180831 1

<h4>Background</h4>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.<h4>Methods</h4>Among all pret ...[more]

PMID: 30170570

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Project description:Background and Purpose- Preterm neonates with intraventricular hemorrhage (IVH) are at risk for posthemorrhagic hydrocephalus and poor neurological outcomes. Iron has been implicated in ventriculomegaly, hippocampal injury, and poor outcomes following IVH. We hypothesized that levels of cerebrospinal fluid blood breakdown products and endogenous iron clearance proteins in neonates with IVH differ from those of neonates with IVH who subsequently develop posthemorrhagic hydrocephalus. Methods- Premature neonates with an estimated gestational age at birth <30 weeks who underwent lumbar puncture for clinical evaluation an average of 2 weeks after birth were evaluated. Groups consisted of controls (n=16), low-grade IVH (grades I-II; n=4), high-grade IVH (grades III-IV; n=6), and posthemorrhagic hydrocephalus (n=9). Control subjects were preterm neonates born at <30 weeks' gestation without brain abnormality or hemorrhage on cranial ultrasound, who underwent lumbar puncture for clinical purposes. Cerebrospinal fluid hemoglobin, total bilirubin, total iron, ferritin, ceruloplasmin, transferrin, haptoglobin, and hemopexin were quantified. Results- Cerebrospinal fluid hemoglobin levels were increased in posthemorrhagic hydrocephalus compared with high-grade IVH (9.45 versus 6.06 µg/mL, P<0.05) and cerebrospinal fluid ferritin levels were increased in posthemorrhagic hydrocephalus compared with controls (511.33 versus 67.08, P<0.01). No significant group differences existed for the other cerebrospinal fluid blood breakdown and iron-handling proteins tested. We observed positive correlations between ventricular enlargement (frontal occipital horn ratio) and ferritin (Pearson r=0.67), hemoglobin (Pearson r=0.68), and total bilirubin (Pearson r=0.69). Conclusions- Neonates with posthemorrhagic hydrocephalus had significantly higher levels of hemoglobin than those with high-grade IVH. Levels of blood breakdown products, hemoglobin, ferritin, and bilirubin correlated with ventricular size. There was no elevation of several iron-scavenging proteins in cerebrospinal fluid in neonates with posthemorrhagic hydrocpehalus, indicative of posthemorrhagic hydrocephalus as a disease state occurring when endogenous iron clearance mechanisms are overwhelmed.

Project description:BackgroundIntraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus (PHH) have a complex pathophysiology involving inflammatory response, ventricular zone and cell-cell junction disruption, and choroid-plexus (ChP) hypersecretion. Increased cerebrospinal fluid (CSF) cytokines, extracellular matrix proteins, and blood metabolites have been noted in IVH/PHH, but osmolality and electrolyte disturbances have not been evaluated in human infants with these conditions. We hypothesized that CSF total protein, osmolality, electrolytes, and immune cells increase in PHH.MethodsCSF samples were obtained from lumbar punctures of control infants and infants with IVH prior to the development of PHH and any neurosurgical intervention. Osmolality, total protein, and electrolytes were measured in 52 infants (18 controls, 10 low grade (LG) IVH, 13 high grade (HG) IVH, and 11 PHH). Serum electrolyte concentrations, and CSF and serum cell counts within 1-day of clinical sampling were obtained from clinical charts. Frontal occipital horn ratio (FOR) was measured for estimating the degree of ventriculomegaly. Dunn or Tukey's post-test ANOVA analysis were used for pair-wise comparisons.ResultsCSF osmolality, sodium, potassium, and chloride were elevated in PHH compared to control (p = 0.012 - < 0.0001), LGIVH (p = 0.023 - < 0.0001), and HGIVH (p = 0.015 - 0.0003), while magnesium and calcium levels were higher compared to control (p = 0.031) and LGIVH (p = 0.041). CSF total protein was higher in both HGIVH and PHH compared to control (p = 0.0009 and 0.0006 respectively) and LGIVH (p = 0.034 and 0.028 respectively). These differences were not reflected in serum electrolyte concentrations nor calculated osmolality across the groups. However, quantitatively, CSF sodium and chloride contributed 86% of CSF osmolality change between control and PHH; and CSF osmolality positively correlated with CSF sodium (r, p = 0.55,0.0015), potassium (r, p = 0.51,0.0041), chloride (r, p = 0.60,0.0004), but not total protein across the entire patient cohort. CSF total cells (p = 0.012), total nucleated cells (p = 0.0005), and percent monocyte (p = 0.016) were elevated in PHH compared to control. Serum white blood cell count increased in PHH compared to control (p = 0.042) but there were no differences in serum cell differential across groups. CSF total nucleated cells also positively correlated with CSF osmolality, sodium, potassium, and total protein (p = 0.025 - 0.0008) in the whole cohort.ConclusionsCSF osmolality increased in PHH, largely driven by electrolyte changes rather than protein levels. However, serum electrolytes levels were unchanged across groups. CSF osmolality and electrolyte changes were correlated with CSF total nucleated cells which were also increased in PHH, further suggesting PHH is a neuro-inflammatory condition.

Project description:BackgroundCerebral intraventricular hemorrhage (IVH) is a major cause of severe neurodevelopmental impairment in preterm infants. To date, no therapy is available that prevents infants from developing serious neurological disability following IVH. Thus, to develop treatment strategies for IVH, it is essential to characterize the initial sequence of molecular events that leads to brain damage. In this study, we investigated extracellular hemoglobin (Hb) as a causal initiator of inflammation in preterm IVH.MethodsUsing a preterm rabbit pup model, we investigated the molecular mechanisms and events following IVH. We also characterized the concentrations of cell-free Hb metabolites and pro-inflammatory mediators in the cerebrospinal fluid (CSF) of preterm human infants and rabbit pups. Finally, Hb metabolites were evaluated as causal initiators of inflammation in primary rabbit astrocyte cell cultures.ResultsFollowing IVH in preterm rabbit pups, the intraventricular CSF concentration of cell-free methemoglobin (metHb) increased from 24 to 72 hours and was strongly correlated with the concentration of TNF? at 72 hours (r2 = 0.896, P <0.001). Also, the mRNA expression of TNF?, IL-1?, and Toll-like receptor-4 and TNF? protein levels were significantly increased in periventricular tissue at 72 hours, which was accompanied by extensive astrocyte activation (that is, glial fibrillary acidic protein (GFAP)staining). Furthermore, exposure of primary rabbit astrocyte cell cultures to metHb caused a dose-dependent increase in TNF? mRNA and protein levels, which was not observed following exposure to oxyhemoglobin (oxyHb) or hemin. Finally, a positive correlation (r2 = 0.237, P <0.03) between metHb and TNF? concentrations was observed in the CSF of preterm human infants following IVH.ConclusionsFollowing preterm IVH, increased metHb formation in the intraventricular space induces expression of pro-inflammatory cytokines. Thus, the formation of metHb might be a crucial initial event in the development of brain damage following preterm IVH. Accordingly, removal, scavenging, or neutralization of Hb could present a therapeutic opportunity and plausible approach to decreasing the damage in the immature brain following preterm IVH.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

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