PMID- 29478510
OWN - NLM
STAT- MEDLINE
DCOM- 20190215
LR  - 20190215
IS  - 1097-6833 (Electronic)
IS  - 0022-3476 (Linking)
VI  - 194
DP  - 2018 Mar
TI  - Plasma Biomarkers of Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy.
PG  - 67-75.e1
LID - S0022-3476(17)31471-3 [pii]
LID - 10.1016/j.jpeds.2017.10.060 [doi]
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]-1beta, IL-6, IL-8, IL-10, IL-12P70, IL-13, 
      interferon-gamma [IFN-gamma], tumor necrosis factor alpha [TNF-alpha], 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-1beta, IL-6, IL-8, IL-10, IL-13, TNF-alpha, and IFN-gamma 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.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Massaro, An N
AU  - Massaro AN
AD  - Department of Pediatrics, The George Washington University School of Medicine and 
      Children's National Health Systems, Washington, DC. Electronic address: 
      anguyenm@cnmc.org.
FAU - Wu, Yvonne W
AU  - Wu YW
AD  - Department of Neurology, University of California, San Francisco, San Francisco, 
      CA; Department of Pediatrics, University of California, San Francisco, San 
      Francisco, CA.
FAU - Bammler, Theo K
AU  - Bammler TK
AD  - Department of Environmental & Occupational Health Sciences, University of 
      Washington, Seattle, WA.
FAU - Comstock, Bryan
AU  - Comstock B
AD  - Department of Biostatistics, University of Washington, Seattle, WA.
FAU - Mathur, Amit
AU  - Mathur A
AD  - Department of Pediatrics, Washington University, St Louis, MO.
FAU - McKinstry, Robert C
AU  - McKinstry RC
AD  - Department of Pediatrics, Washington University, St Louis, MO; Department of 
      Radiology, Washington University, St Louis, MO.
FAU - Chang, Taeun
AU  - Chang T
AD  - Department of Pediatrics, The George Washington University School of Medicine and 
      Children's National Health Systems, Washington, DC; Department of Neurology, The 
      George Washington University School of Medicine and Children's National Health 
      Systems, Washington, DC.
FAU - Mayock, Dennis E
AU  - Mayock DE
AD  - Department of Pediatrics, University of Washington, Seattle, WA.
FAU - Mulkey, Sarah B
AU  - Mulkey SB
AD  - Department of Pediatrics, The George Washington University School of Medicine and 
      Children's National Health Systems, Washington, DC; Department of Neurology, The 
      George Washington University School of Medicine and Children's National Health 
      Systems, Washington, DC.
FAU - Van Meurs, Krisa
AU  - Van Meurs K
AD  - Department of Pediatrics, Stanford University, Palo Alto, CA.
FAU - Juul, Sandra
AU  - Juul S
AD  - Department of Pediatrics, University of Washington, Seattle, WA.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Pediatr
JT  - The Journal of pediatrics
JID - 0375410
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cytokines)
RN  - 0 (tau Proteins)
RN  - 11096-26-7 (Erythropoietin)
SB  - IM
CIN - J Pediatr. 2018 Mar;194:3. PMID: 29478504
MH  - Biomarkers/blood
MH  - Brain Injuries/*blood/diagnostic imaging/etiology
MH  - Brain-Derived Neurotrophic Factor/blood
MH  - Cytokines/blood
MH  - Erythropoietin/therapeutic use
MH  - Humans
MH  - Hypoxia-Ischemia, Brain/*blood/complications/drug therapy
MH  - Infant, Newborn
MH  - Magnetic Resonance Imaging
MH  - tau Proteins/blood
OTO - NOTNLM
OT  - cytokine
OT  - erythropoietin
OT  - hypothermia
OT  - magnetic resonance imaging
OT  - neurodevelopment
OT  - tau protein
OT  - therapeutic
EDAT- 2018/02/27 06:00
MHDA- 2019/02/16 06:00
CRDT- 2018/02/27 06:00
PHST- 2017/06/20 00:00 [received]
PHST- 2017/09/21 00:00 [revised]
PHST- 2017/10/25 00:00 [accepted]
PHST- 2018/02/27 06:00 [entrez]
PHST- 2018/02/27 06:00 [pubmed]
PHST- 2019/02/16 06:00 [medline]
AID - S0022-3476(17)31471-3 [pii]
AID - 10.1016/j.jpeds.2017.10.060 [doi]
PST - ppublish
SO  - J Pediatr. 2018 Mar;194:67-75.e1. doi: 10.1016/j.jpeds.2017.10.060.