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

Abstract

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).

Keywords: cerebrospinal fluid; ferritin; intraventricular hemorrhage; iron; posthemorrhagic hydrocephalus.

FIG. 1.

Nonlinear temporal trends in Hb, ferritin, total iron, total bilirubin, and total protein adjusted for estimated gestational age at birth, demonstrating nonlinear decrements in Hb and Hb degradation products in CSF with serial ventricular taps. Figure is available in color online only.

FIG. 2.

Temporal trends in CSF ferritin and total iron differed between neonates with moderate ventriculomegaly (FOHR ≤ 0.6) and those with severe ventriculomegaly (FOHR > 0.6) at the first CSF tap. Compared to neonates with moderate ventriculomegaly at the initial CSF tap, the neonates with severe ventriculomegaly demonstrated higher initial values of CSF ferritin and total iron, with decreases in these values over time with serial ventricular taps. However, temporal trends in Hb, total bilirubin, and total protein did not differ significantly between the groups. Figure is available in color online only.

FIG. 3.

Linear regression of initial ventriculomegaly (FOHR at first CSF tap) against CSF ferritin (ng/ml) at first CSF tap. Higher levels of CSF ferritin at the initial CSF tap were associated with more severe ventricular enlargement at the initial CSF tap (higher FOHR). Figure is available in color online only.