TY - JOUR
T1 - Plasma Biomarkers of Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy
AU - Massaro, An N.
AU - Wu, Yvonne W.
AU - Bammler, Theo K.
AU - Comstock, Bryan
AU - Mathur, Amit
AU - McKinstry, Robert C.
AU - Chang, Taeun
AU - Mayock, Dennis E.
AU - Mulkey, Sarah B.
AU - Van Meurs, Krisa
AU - Juul, Sandra
N1 - Funding Information:
Funded by the Cerebral Palsy Alliance Research Foundation and the Thrasher Research Fund . The authors declare no conflicts of interest.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
KW - cytokine
KW - erythropoietin
KW - hypothermia
KW - magnetic resonance imaging
KW - neurodevelopment
KW - tau protein
KW - therapeutic
UR - http://www.scopus.com/inward/record.url?scp=85044672118&partnerID=8YFLogxK
U2 - 10.1016/j.jpeds.2017.10.060
DO - 10.1016/j.jpeds.2017.10.060
M3 - Article
C2 - 29478510
AN - SCOPUS:85044672118
SN - 0022-3476
VL - 194
SP - 67-75.e1
JO - Journal of Pediatrics
JF - Journal of Pediatrics
ER -