Poor Correlation Between Inflammatory and Brain Injury Biomarkers After Neonatal Intraventricular Hemorrhage: A Pilot Study.

Abstract

Background: This study investigated changes in hemoglobin, neuroinflammatory and brain injury biomarkers (Tumor necrosis factor-alpha (TNF-α) and glial fibrillary acidic protein (GFAP)) in early stages of cerebrospinal fluid (CSF) diversion in preterm neonates with intraventricular hemorrhage (IVH). We hypothesized that patients with higher CSF hemoglobin levels would have higher TNF-α and GFAP levels.

Methods: This prospective study included infants with grade 3 or 4 IVH. All had ventricular reservoirs were placed following standard neurosurgical care. The first CSF sample was collected day of reservoir placement. Subsequent samples were from clinically indicated CSF withdraws to decompress ventricles. Enzyme-linked Immunosorbent Assays were performed using commercially available kits and standard methods.

Results: Eight preterm infants were included in the study. Median post-menstrual age was 26.3 weeks, and median birth weight was 765 grams. No biomarkers investigated had a significant correlation with days since reservoir placement. 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 lost when the power of repeated measures analysis was leveraged (repeated measures correlation r = -0.473, p=0.055, Bonferroni adjusted alpha level =0.008).

Conclusions: This study found no significant correlation between CSF hemoglobin, TNF-α, and GFAP in the first weeks of CSF diversion in neonates with IVH. There is high variability of these measures, even within subjects. This study reveals the need for further research into neuroinflammatory and brain injury biomarkers in neonates with IVH, their usefulness in clinical decision making, and long-term outcomes.