UCH-L1 and GFAP Serum Levels in Neonates with Hypoxic-Ischemic Encephalopathy: A Single Center Pilot Study

Abstract

Objective: We examined two potential biomarkers of brain damage in hypoxic-ischemic encephalopathy (HIE) neonates: glial fibrillary acidic protein (GFAP; a marker of gliosis) and ubiquitin C-terminal hydrolase L1 (UCH-L1; a marker of neuronal injury). We hypothesized that the biomarkers would be measurable in cord blood of healthy neonates and could serve as a normative reference for brain injury in HIE infants. We further hypothesized that higher levels would be detected in serum samples of HIE neonates and would correlate with brain damage on magnetic resonance imaging (MRI) and later developmental outcomes.?

Study design: Serum UCH-L1 and GFAP concentrations from HIE neonates (n = 16) were compared to controls (n = 11). The relationship between biomarker concentrations of HIE neonates and brain damage (MRI) and developmental outcomes (Bayley-III) was examined using Pearson correlation coefficients and a mixed model design.

Result: Both biomarkers were detectable in cord blood from control subjects. UCH-L1 concentrations were higher in HIE neonates (p < 0.001), and associated with cortical injury (p < 0.055) and later motor and cognitive developmental outcomes (p < 0.05). The temporal change in GFAP concentrations during (from birth to 96 h of age) predicted motor developmental outcomes (p < 0.05) and injury to the basal ganglia and white matter.

Conclusion: Ubiquitin C-terminal hydrolase L1 and GFAP should be explored further as promising serum biomarkers of brain damage and later neurodevelopmental outcomes in neonates with HIE.

Keywords: GFAP; HIE; UCH-L1; biomarkers.

Figure 1

The serum concentrations of UCH-L1 (A) and GFAP (B) in neonates with HIE are compared with control neonates. Increased serum levels of UCH-L1 at 0–6 h in HIE patients (n = 4) compared with controls (n = 11), p < 0.0001. The serum concentration of GFAP did not differ statistically from the control population.

Figure 2

Receiver–operator characteristic plots of UCH-L1 and GFAP at different time point in detecting HIE. Area under curve (AUC with 95% confidence interval) for UCH-L1 is 1.00, 0.83 (0.57–1.00), and 0.73 (0.51–0.94) for 0–6, 12, and 24 h, respectively. AUC (95% CI) for GFAP is 0.58 (0.15–1.00), 0.61 (0.33–0.88), and 0.64 (0.41–0.87) for 0–6, 12, and 24 h, respectively.

Figure 3

The serum concentrations of UCH-L1 and GFAP in neonates with HIE are plotted over the time of sample collection. The serum concentrations are expressed as the mean ± SEM. The serum concentration of UCH-L1 decreased rapidly over the initial 24 h with the highest concentrations obtained at 0–6 h (A). The serum concentrations of GFAP increased over the 96 h of sampling (B).

Figure 4

The serum concentrations of UCH-L1 (A) and GFAP (B) in neonates with HIE who had good (black boxes and lines) and poor developmental outcomes (gray boxes and lines) are plotted over the 96 h sampling period. The mean serum concentrations are represented by the line while the bar represents the minimum and maximum serum concentrations.