P2.104: Cerebrospinal Fluid Diversion in Neonatal Intraventricular Hemorrhage Does Not Reduce Biomarkers of Brain Inflammation and Injury

Background: Children born prematurely are at increased risk for intraventricular hemorrhage (IVH). Approximately one-third of neonates with IVH develop post-hemorrhagic hydrocephalus (PHH), and 10% to 20% require surgical procedures like a ventricular reservoir or ventriculoperitoneal shunt placement. Cytokines are essential components of inflammatory processes, and elevated levels of tumor necrosis factor-alpha (TNF-α) in the cerebrospinal fluid (CSF) have been associated with IVH and increased risk of PHH. Glial fibrillary acidic protein (GFAP) is a structural protein found in astrocytes and released into the CSF when astrocytes are injured. Cell-free hemoglobin and its degradation products have been associated with the causation of secondary brain injury.

IVH and ventricular enlargement lead to periventricular tissue compression, ischemia, and hypoxia, progressing to neuroinflammation and axonal degeneration, leading to cell death. CSF diversion in these patients relieves increased intracranial pressure, decreasing injury, ischemia, and inflammation. Thus, we expected a downward trend of neuroinflammatory biomarkers over time.

This study investigated the trend of hemoglobin and neuroinflammatory biomarkers and cytokines (GFAP and TNF-α) in the early weeks of CSF diversion in preterm neonates with IVH.

Methods: This prospective, observational, single-center study was conducted at an urban tertiary care center. IRB approval was obtained. The patients comprised infants with grade 3 or grade 4 IVH. All the patients had ventricular reservoirs placed as a part of neurosurgical care. The first sample was collected on the day of reservoir placement. CSF was routinely withdrawn from these patients to decompress their ventricles, and samples collected 1-3 weeks after reservoir placement were analyzed for each patient. An Enzyme-linked Immunosorbent Assay was performed using commercially available kits.

Results: Eight preterm infants were included in the study. Their median post-menstrual age (PMA) was 26.3 weeks, and their median birth weight was 765 grams. The median PMA at the time of reservoir placement was 30.64 weeks. No variables of interest significantly correlated with days since reservoir placement (Figure 1). Initially, GFAP and hemoglobin were significantly correlated (Pearson’s r = -0.682, p< 0.001), so a linear regression was conducted (slope = -0.00363). However, this relationship was no longer evident when the power of repeated measures analysis was leveraged (repeated measures correlation r = -0.473, p = 0.055).

Conclusion: This study found no significant correlation between CSF TNF-α, GFAP, and hemoglobin in the early weeks of CSF diversion in neonates with IVH. There is high variability of these measures, even within subjects. Researchers should be cautious when using single CSF biomarker measures to predict outcomes or assess treatment response for neonatal IVH. Our study offers important insights into the intricate biochemical environment of the CSF after IVH. It highlights the need for future studies with larger cohorts and CSF analysis over an extended period with additional brain injury markers.