Elevated cerebrospinal fluid iron and ferritin associated with early severe ventriculomegaly in preterm posthemorrhagic hydrocephalus

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  • 1 Department of Neurosurgery, Stanford University School of Medicine, Stanford, California;
  • | 2 Department of Neurological Surgery, Washington University School of Medicine;
  • | 3 Department of Pediatrics, Washington University School of Medicine;
  • | 4 Department of Neurology, Washington University School of Medicine;
  • | 5 Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri; and
  • | 6 Quantitative Sciences Unit, Stanford Center for Biomedical Informatics Research (BMIR), Stanford University, Stanford, California
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OBJECTIVE

Posthemorrhagic hydrocephalus (PHH) following preterm intraventricular hemorrhage (IVH) is among the most severe sequelae of extreme prematurity and a significant contributor to preterm morbidity and mortality. The authors have previously shown hemoglobin and ferritin to be elevated in the lumbar puncture cerebrospinal fluid (CSF) of neonates with PHH. Herein, they evaluated CSF from serial ventricular taps to determine whether neonates with PHH following severe initial ventriculomegaly had higher initial levels and prolonged clearance of CSF hemoglobin and hemoglobin degradation products compared to those in neonates with PHH following moderate initial ventriculomegaly.

METHODS

In this observational cohort study, CSF samples were obtained from serial ventricular taps in premature neonates with severe IVH and subsequent PHH. CSF hemoglobin, ferritin, total iron, total bilirubin, and total protein were quantified using ELISA. Ventriculomegaly on cranial imaging was assessed using the frontal occipital horn ratio (FOHR) and was categorized as severe (FOHR > 0.6) or moderate (FOHR ≤ 0.6).

RESULTS

Ventricular tap CSF hemoglobin (mean) and ferritin (initial and mean) were higher in neonates with severe versus moderate initial ventriculomegaly. CSF hemoglobin, ferritin, total iron, total bilirubin, and total protein decreased in a nonlinear fashion over the weeks following severe IVH. Significantly higher levels of CSF ferritin and total iron were observed in the early weeks following IVH in neonates with severe initial ventriculomegaly than in those with initial moderate ventriculomegaly.

CONCLUSIONS

Among preterm neonates with PHH following severe IVH, elevated CSF hemoglobin, ferritin, and iron were associated with more severe early ventricular enlargement (FOHR > 0.6 vs ≤ 0.6 at first ventricular tap).

ABBREVIATIONS

CSF = cerebrospinal fluid; FOHR = frontal occipital horn ratio; Hb = hemoglobin; IVH = intraventricular hemorrhage; PHH = posthemorrhagic hydrocephalus.

Supplementary Materials

    • Supplemental Figure (PDF 6,184 KB)

Images from Oushy et al. (pp 195–202).

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