title: Biomarkers for severity of neonatal hypoxic-ischemic encephalopathy and outcomes in newborns receiving hypothermia therapy.
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.
  
  
  METHODS
  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.
authors: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: lina.chalak@utsouthwestern.edu.
authors: Lina F
authors: LF
authors: Chalak
authors: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Pablo J
authors: PJ
authors: Sánchez
authors: Department of Clinical Sciences and Statistics, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Beverley
authors: B
authors: Adams-Huet
authors: Department of Pediatrics, Brown University, Women & Infants Hospital of Rhode Island, Providence, RI.
authors: Abbot R
authors: AR
authors: Laptook
authors: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Roy J
authors: RJ
authors: Heyne
authors: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Charles R
authors: CR
authors: Rosenfeld
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D001034:Apgar Score; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000473:pathology; D002547:Cerebral Palsy / Q000453:epidemiology; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000097:blood*; D002658:Developmental Disabilities / Q000453:epidemiology; D004569:Electroencephalography; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005904:Glial Fibrillary Acidic Protein / Q000097:blood*; D006801:Humans; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000097:blood* / Q000628:therapy*; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D009460:Neurologic Examination; D010865:Pilot Projects; D011446:Prospective Studies; D017694:Rewarming; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D043222:Ubiquitin Thiolesterase / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D015415:Biomarkers; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; C507533:Ubiquitin carboxyl-Terminal Hydrolase L-1, human; D042461:Vascular Endothelial Growth Factor A; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D043222:Ubiquitin Thiolesterase