Urinary S100B protein measurements: A tool for the early identification of hypoxic-ischemic encephalopathy in asphyxiated full-term infants

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Abstract
Objective Hypoxic-ischemic encephalopathy (HIE) is one of the major causes of perinatal mortality and morbidity. To date, there are no reliable methods to detect which infants will develop brain damage after asphyxia insult. Design and Setting Prospective study conducted in three tertiary departments of neonatology from December 1999 to July 2002. Participants A total of 44 infants with perinatal asphyxia and 68 control infants. Intervention Routine laboratory variables, neurologic patterns, ultrasound imaging, and urine concentrations of S100B protein were determined at nine time points. Main Outcome Measures The concentrations of S100B protein in urine were measured using an immunoluminometric assay at first urination and 4, 8, 12, 16, 20, 24, 48, and 72 hrs after birth. The results were correlated with the presence or absence of hypoxic-ischemic encephalopathy. Routine laboratory parameters and neurologic patterns were assessed at the same time as urine sampling. Results S100B protein levels were significantly higher in samples collected at all monitoring time points from newborns with perinatal asphyxia with or without hypoxic-ischemic encephalopathy than in samples from normal infants (all p < .001). When asphyxiated infants were subdivided according to the presence of mild or absence of hypoxic-ischemic encephalopathy (group A) and of moderate or severe hypoxic-ischemic encephalopathy (group B), S100B levels were significantly higher at all the predetermined monitoring time points in group B infants than group A or control infants (all p < .001). An S100B concentration cutoff of 0.41 μg/L at first urination had a sensitivity of 91.3% and a specificity of 94.6% for predicting the development of hypoxic-ischemic encephalopathy. The sensitivity and specificity of measurements obtained from 4 to 72 hrs after birth were up to 100% and 98.8%, respectively. Conclusions Longitudinal S100B protein measurements in urine soon after birth are a useful tool to identify which asphyxiated infants are at risk of hypoxic-ischemic encephalopathy and its possible neurologic sequelae.