Plasma Biomarkers of Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy.

Abstract

OBJECTIVES:

To evaluate plasma brain specific proteins and cytokines as biomarkers of brain injury in newborns with hypoxic-ischemic encephalopathy (HIE) and, secondarily, to assess the effect of erythropoietin (Epo) treatment on the relationship between biomarkers and outcomes.

STUDY DESIGN:

A study of candidate brain injury biomarkers was conducted in the context of a phase II multicenter randomized trial evaluating Epo for neuroprotection in HIE. Plasma was collected at baseline (<24 hours) and on day 5. Brain injury was assessed by magnetic resonance imaging (MRI) and neurodevelopmental assessments at 1 year. The relationships between Epo, brain-specific proteins (S100B, ubiquitin carboxy-terminal hydrolase-L1 [UCH-L1], total Tau, neuron specific enolase), cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, IL-12P70, IL-13, interferon-gamma [IFN-γ], tumor necrosis factor alpha [TNF-α], brain-derived neurotrophic factor [BDNF], monocyte chemoattractant protein-1), and brain injury were assessed.

RESULTS:

In 50 newborns with encephalopathy, elevated baseline S100B, Tau, UCH-L1, IL-1β, IL-6, IL-8, IL-10, IL-13, TNF-α, and IFN-γ levels were associated with increasing brain injury severity by MRI. Higher baseline Tau and lower day 5 BDNF were associated with worse 1 year outcomes. No statistically significant evidence of Epo treatment modification on biomarkers was detected in this small cohort.

CONCLUSIONS:

Elevated plasma brain-specific proteins and cytokine levels in the first 24 hours of life are associated with worse brain injury by MRI in newborns with HIE. Only Tau and BDNF levels were found to be related to neurodevelopmental outcomes. The effect of Epo treatment on the relationships between biomarkers and brain injury in HIE requires further study.

TRIAL REGISTRATION:

ClinicalTrials.gov: 01913340.

• Authors: An N Massaro, Yvonne W Wu, Theo K Bammler, Bryan Comstock, Amit Mathur, Robert C McKinstry, Taeun Chang, Dennis E Mayock, Sarah B Mulkey, Krisa Van Meurs, Sandra Juul
• Journal: The Journal of pediatrics (J Pediatr) Vol. 194 Pg. 67-75.e1 (03 2018) ISSN: 1097-6833 [Electronic] United States
• PMID: 29478510 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Brain-Derived Neurotrophic Factor
• Cytokines
• tau Proteins
• Erythropoietin

Topics

• Biomarkers (blood)
• Brain Injuries (blood, diagnostic imaging, etiology)
• Brain-Derived Neurotrophic Factor (blood)
• Cytokines (blood)
• Erythropoietin (therapeutic use)
• Humans
• Hypoxia-Ischemia, Brain (blood, complications, drug therapy)
• Infant, Newborn
• Magnetic Resonance Imaging
• tau Proteins (blood)