ABSTRACT
Newborn infants with perinatal asphyxia are prone to the development of hypoxic-ischemic encephalopathy [HIE]. To date, there are no reliable methods for proper identification of infants who are at high risk of HIE after asphyxial insult. We sought to evaluate urinary levels of a lipid peroxidation marker, 8-isoprostane, and a brain specific protein, S100B protein, as non-invasive tools that might help early identification of postasphyxial hypoxic-ischemic brain damage and prediction of its outcome. Thirty term neonates with perinatal asphyxia were evaluated in comparison to 15 matched healthy controls. Urinary concentrations of 8-isoprostane [by ELISA] and S100B protein [by immunoluminometric technique] were determined at first urination [time 1] and repeated in a second sample obtained 24-48 hours postnatally [time 2]. Asphyxiated neonates were clinically monitored for their neurological pattern over the first two postnatal weeks and were subsequently classified as mild [grade I, n=8], moderate [grade II, n=12] and severe [grade III, n=10] HIE. Eleven of these neonates [36.7%] died in the NICU. The results obtained were interpreted in relation to the grade of HIE severity and mortality. Urinary concentrations of 8-isoprostane and S100B protein were significantly higher in asphyxiated neonates at both monitored times, as compared to controls. Levels of both markers were related to the grade of HIE severity being significantly higher in neonates who developed grade II as compared to grade I, while highest levels were found in grade III. A significant increase in urinary 8-isoprostane from time 1 to time 2 was only found in grade III [p<0.05] while S100B protein increased over that time period in grades II and III [p<0.01, respectively]. Survivors showed significantly lower mean level of each marker as compared to those with fatal outcome [p<0.001, respectively], at both monitored times. Diagnostic performance tests revealed that S100B protein was superior to 8-isoprostane, at the two monitored times, for prediction of HIE severity and mortality. At first urination, a cut-off value for S100B protein of 0.3 micro g/L could best predict development of grades II and III HIE with a positive predictive value [PPV] of 100% and an efficacy of 95.5%. Meanwhile, an optimum cut-off value of 6.89 microg/mg creatinine for 8-isoprostane, had a PPV of 90.48% and an efficacy of 88.89% for grades II and III prediction. As predictors of mortality at first urination, an optimum cut-off value for S100B protein of 2.12 micro g/L and for 8-isoprostane of 10.4 micro g/mg creatinine had corresponding PPVs of 90.9% and 90%, respectively and efficacies of 93.3% and 90%, respectively. There was no significant difference in the overall diagnostic performance of each of the two markers either for disease severity or mortality prediction between both monitored times [p>0.05, respectively]. 8-isoprostane and S100B protein levels are increased in urine following birth asphyxia. S100B protein is superior to 8-isoprostane for prediction of both HIE severity and mortality. It could be speculated that measurement of urinary concentrations of these markers, soon after birth, could serve as a clinically useful and relatively simple non-invasive tool to predict the risk for developing HIE following birth asphyxia and its short-term outcome