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Published on: August 25, 2022
Elevated cerebrospinal fluid iron and ferritin associated with early severe ventriculomegaly in preterm
Kelly B Mahaney1, Chandana Buddhala2, Mounica Paturu2
11Department of Neurosurgery, Stanford University School of Medicine, Stanford, California.
Insights
In preterm infants with posthemorrhagic hydrocephalus (PHH) after intraventricular hemorrhage (IVH), higher initial levels of cerebrospinal fluid (CSF) hemoglobin and ferritin correlate with more severe ventricular enlargement. These markers indicate prolonged clearance in severe cases.
Area of Science:
- Neonatal neurology
- Pediatric neurosurgery
- Critical care medicine
Background:
- Posthemorrhagic hydrocephalus (PHH) is a severe complication of preterm intraventricular hemorrhage (IVH).
- Previous studies indicated elevated hemoglobin and ferritin in the cerebrospinal fluid (CSF) of neonates with PHH.
- Understanding the dynamics of these markers is crucial for managing PHH in extremely premature infants.
Purpose of the Study:
- To investigate whether neonates with PHH following severe initial ventriculomegaly exhibit higher initial levels and slower clearance of CSF hemoglobin and its degradation products compared to those with moderate initial ventriculomegaly.
- To correlate early ventricular enlargement severity with CSF biochemical markers in preterm neonates with PHH.
Main Methods:
- An observational cohort study involving premature neonates with severe IVH and subsequent PHH.
- CSF samples were collected via serial ventricular taps and analyzed for hemoglobin, ferritin, total iron, total bilirubin, and total protein using ELISA.
- Ventriculomegaly was quantified using the frontal occipital horn ratio (FOHR), categorizing it as severe (FOHR > 0.6) or moderate (FOHR ≤ 0.6).
Main Results:
- Higher mean CSF hemoglobin and initial/mean ferritin levels were observed in neonates with severe initial ventriculomegaly compared to those with moderate ventriculomegaly.
- CSF hemoglobin, ferritin, total iron, total bilirubin, and total protein showed nonlinear decreases over several weeks post-IVH.
- Elevated CSF ferritin and total iron were noted in the early weeks following IVH in the severe ventriculomegaly group.
Conclusions:
- In preterm neonates with PHH following severe IVH, elevated CSF hemoglobin, ferritin, and iron are linked to more severe early ventricular enlargement.
- These findings highlight the association between specific CSF biochemical markers and the degree of ventricular enlargement in PHH.
- The study provides insights into the biochemical milieu of PHH and its relationship to hydrocephalus severity.
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).
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