Early Biochemical Indicators of Hypoxic-Ischemic Encephalopathy after Birth Asphyxia

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Abstract
Hypoxic-ischemic encephalopathy (HIE) after perinatal asphyxia is a condition in which serum concentrations of brain-specific biochemical markers may be elevated. Neuroprotective interventions in asphyxiated newborns require early indicators of brain damage to initiate therapy. We examined brain-specific creatine kinase (CK-BB), protein S-100, and neuron-specific enolase in cord blood and 2, 6, 12, and 24 h after birth in 29 asphyxiated and 20 control infants. At 2 h after birth, median (quartiles) serum CK-BB concentration was 10.0 U/L (6.0–13.0 U/L) in control infants, 16.0 U/L (13.0–23.5 U/L) in infants with no or mild HIE, and 46.5 U/L (21.4–83.0 U/L) in infants with moderate or severe HIE. Serum protein S-100 was 1.6 μg/L (1.4–2.5 μg/L) in control infants, 2.9 μg/L (1.8–4.7 μg/L) in asphyxiated infants with no or mild HIE, and 17.0 μg/L (3.2–34.1 μg/L) in infants with moderate or severe HIE 2 h after birth. No significant difference was detectable in serum neuron-specific enolase between infants with no or mild and moderate or severe HIE 2 and 6 h after birth. A combination of serum protein S-100 (cutoff value, 8.5 μg/L) and CK-BB (cutoff value, 18.8 U/L) 2 h after birth had the highest predictive value (83%) and specificity (95%) of predicting moderate and severe HIE. Cord blood pH (cutoff value, 17 mM) increase the predictive values of protein S-100 and CK-BB. We conclude that elevated serum concentrations of protein S-100 and CK-BB reliably indicate moderate and severe HIE as early as 2 h after birth.