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Serum Biomarkers of MRI Brain Injury in Neonatal Hypoxic Ischemic Encephalopathy Treated With Whole-Body Hypothermia: A Pilot Study

Massaro, An N. MD1; Jeromin, Andreas PhD2; Kadom, Nadja MD3; Vezina, Gilbert MD3; Hayes, Ronald L. PhD2; Wang, Kevin K. W. PhD2; Streeter, Jackson MD2; Johnston, Michael V. MD4

Pediatric Critical Care Medicine: March 2013 - Volume 14 - Issue 3 - p 310–317
doi: 10.1097/PCC.0b013e3182720642
Neurocritical Care

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.

1Department of Neonatology, Children’s National Medical Center, WA.

2Banyan Biomarkers, Alachua, FL.

3Department ofNeuroradiology, Children’s National Medical Center, WA.

4Department of Neuroscience, The Hugo W. Moser Research Institute at Kennedy-Krieger, Baltimore, MD.

Supported, in part, by the Pediatric Clinical Research Scholars Award (5K12RR17613-05, Dr. Massaro) and the Clinical and Translational Science Institute at Children’s National (1KL2RR031987-01, Dr. Massaro)

Drs. Jeromin, Hayes, Wang, and Streeter are employees of Banyan Biomarkers, Inc. in Alachua, FL, and disclose a competing financial interest. The remaining authors have not disclosed any potential conflicts of interest.

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©2013The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies