Biomarkers for severity of neonatal hypoxic-ischemic encephalopathy and outcomes in newborns receiving hypothermia therapy

J Pediatr. 2014 Mar;164(3):468-74.e1. doi: 10.1016/j.jpeds.2013.10.067. Epub 2013 Dec 12.

Abstract

Objective: To evaluate serum neuronal and inflammatory biomarkers to determine whether measurements of umbilical cords at birth can stratify severity of hypoxic-ischemic encephalopathy (HIE), whether serial measurements differ with hypothermia-rewarming, and whether biomarkers correlate with neurological outcomes.

Study design: This is a prospective cohort of inborn term newborns with varying degrees of HIE by neurological assessment. Neuronal glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1, and inflammatory cytokines were measured in serum from umbilical artery at 6-24, 48, 72, and 78 hours of age. Neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development-III scales) were performed at 15-18 months.

Results: Twenty neonates had moderate (n = 17) or severe (n = 3) HIE and received hypothermia; 7 had mild HIE and were not cooled. At birth, serum GFAP and ubiquitin carboxyl-terminal hydrolase L1 increased with the severity of HIE (P < .001), and serial GFAP remained elevated in neonates with moderate to severe HIE. Interleukin (IL)-6, IL-8, and vascular endothelial growth factor were greater at 6-24 hours in moderate to severe vs mild HIE (P < .05). The serial values were unaffected by hypothermia-rewarming. Elevated GFAP, IL-1, IL-6, IL-8, tumor necrosis factor, interferon, and vascular endothelial growth factor at 6-24 hours were associated with abnormal neurological outcomes.

Conclusions: The severity of the hypoxic-ischemic injury can be stratified at birth because elevated neuronal biomarkers in cord serum correlated with severity of HIE and outcomes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Apgar Score
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood
  • Brain / pathology
  • Cerebral Palsy / epidemiology
  • Creatinine / blood
  • Cytokines / blood*
  • Developmental Disabilities / epidemiology
  • Electroencephalography
  • Female
  • Fetal Blood / chemistry
  • Glial Fibrillary Acidic Protein / blood*
  • Humans
  • Hypothermia, Induced*
  • Hypoxia-Ischemia, Brain / blood*
  • Hypoxia-Ischemia, Brain / therapy*
  • Infant, Newborn
  • Magnetic Resonance Imaging
  • Male
  • Neurologic Examination
  • Pilot Projects
  • Prospective Studies
  • Rewarming
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Ubiquitin Thiolesterase / blood*
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Biomarkers
  • Cytokines
  • Glial Fibrillary Acidic Protein
  • Ubiquitin carboxyl-Terminal Hydrolase L-1, human
  • Vascular Endothelial Growth Factor A
  • Creatinine
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Ubiquitin Thiolesterase