title: Biomarkers of brain injury in neonatal encephalopathy treated with hypothermia.
abstract: OBJECTIVE
  To determine if early serum S100B and neuron-specific enolase (NSE) levels are associated with neuroradiographic and clinical evidence of brain injury in newborns with encephalopathy.
  
  
  METHODS
  Patients who received therapeutic whole-body hypothermia were prospectively enrolled in this observational study. Serum specimens were collected at 0, 12, 24, and 72 hours of cooling. S100B and NSE levels were measured by enzyme linked immunosorbent assay. Magnetic resonance imaging was performed in surviving infants at 7-10 days of life. Standardized neurologic examination was performed by a child neurologist at 14 days of life. Multiple linear regression analyses were performed to evaluate the association between S100B and NSE levels and unfavorable outcome (death or severe magnetic resonance imaging injury/significant neurologic deficit). Cutoff values were determined by receiver operating curve analysis.
  
  
  RESULTS
  Newborns with moderate to severe encephalopathy were enrolled (n = 75). Median pH at presentation was 6.9 (range, 6.5-7.35), and median Apgar scores of 1 at 1 minute, 3 at 5 minutes, and 5 at 10 minutes. NSE and S100B levels were higher in patients with unfavorable outcomes across all time points. These results remained statistically significant after controlling for covariables, including encephalopathy grade at presentation, Apgar score at 5 minutes of life, initial pH, and clinical seizures.
  
  
  CONCLUSIONS
  Elevated serum S100B and NSE levels measured during hypothermia were associated with neuroradiographic and clinical evidence of brain injury in encephalopathic newborns. These brain-specific proteins may be useful immediate biomarkers of cerebral injury severity.
authors.affiliation: Department of Neonatology, Children's National Medical Center, Washington, DC, USA.
authors.forename: An N
authors.initials: AN
authors.lastname: Massaro
authors.forename: Taeun
authors.initials: T
authors.lastname: Chang
authors.forename: Nadja
authors.initials: N
authors.lastname: Kadom
authors.forename: Tammy
authors.initials: T
authors.lastname: Tsuchida
authors.forename: Joseph
authors.initials: J
authors.lastname: Scafidi
authors.forename: Penny
authors.initials: P
authors.lastname: Glass
authors.forename: Robert
authors.initials: R
authors.lastname: McCarter
authors.forename: Stephen
authors.initials: S
authors.lastname: Baumgart
authors.forename: Gilbert
authors.initials: G
authors.lastname: Vezina
authors.forename: Karin B
authors.initials: KB
authors.lastname: Nelson
mesh_terms: D001034:Apgar Score; D001238:Asphyxia Neonatorum / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D001927:Brain Diseases / Q000097:blood*; D001930:Brain Injuries / Q000097:blood*; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D009414:Nerve Growth Factors / Q000097:blood*; D009460:Neurologic Examination; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D012372:ROC Curve; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood*
chemical_list: D015415:Biomarkers; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D010751:Phosphopyruvate Hydratase