Serum biomarkers of MRI brain injury in neonatal hypoxic ischemic encephalopathy treated with whole-body hypothermia: A pilot study

Objectives: To determine if candidate biomarkers, ubiquitin carboxyl-terminal esterase L1 and glial fibrillary acidic protein, are elevated in neonates with hypoxic ischemic encephalopathy who die or have severe MRI injury compared with surviving infants with minimal or no injury on brain MRI. Design: Prospective observational study. Setting: Level IIIC outborn neonatal ICU in a free-standing children's hospital. Patients: Term newborns with moderate-to-severe hypoxic ischemic encephalopathy referred for therapeutic hypothermia Interventions: Serum specimens were collected at 0, 12, 24, and 72 hours of cooling. MRI was performed in surviving infants at target 7-10 days of life and was scored by a pediatric neuroradiologist masked to biomarker and clinical data. Measurements and Main Results: Serial biomarker levels were determined in 20 hypoxic ischemic encephalopathy patients. Ubiquitin carboxyl-terminal esterase L1 was higher at initiation and 72 hours of cooling, while glial fibrillary acidic protein was higher at 24 and 72 hours in babies with adverse outcome compared with those with favorable outcome. Conclusions: This preliminary data support further studies to evaluate ubiquitin carboxyl-terminal esterase L1 and glial fibrillary acidic protein as immediate biomarkers of cerebral injury severity in newborns with hypoxic ischemic encephalopathy.