Evaluation of Urinary S100B Protein Level and Lactate/Creatinine Ratio for Early Diagnosis and Prognostic Prediction of Neonatal Hypoxic-Ischemic Encephalopathy

Abstract

Background: Early identification and prevention of hypoxic-ischemic encephalopathy (HIE) in newborns may reduce neonatal mortality and neurological dysfunction. Objective: To analyze the diagnostic and prognostic values of urinary S100B level and lactate/creatinine ratio in newborns with HIE. Methods: Seventy-eight full-term newborns with HIE and 25 normal newborns were enrolled. The Neonatal Behavioral Neurological Assessment (NBNA) and Developmental Screening Test were scored. The concentration of urinary S100B protein was determined using the S100B enzyme-linked immunosorbent assay and the levels of urinary lactate and creatinine were measured with the enzyme colorimetric method. Results: Urinary S100B level on days 1–3 after birth and lactate/creatinine ratio on day 1 were significantly higher in newborns with HIE than those in the control group. Both indexes were positively correlated with the clinical grading of HIE. A cutoff value for the S100B level of 0.47 μg/l on day 3 after birth had a sensitivity of 90% and specificity of 92% for prediction of HIE. A lactate/creatinine ratio of more than 0.55 on day 1 showed the highest sensitivity (92%) and specificity (90%). A combination of both indexes improved the sensitivity and specificity to 99 and 97%, respectively. A negative correlation of both lactate/creatinine ratio on day 1 and S100B level on days 1–3 after birth with the NBNA score was identified on days 3, 7 and 14 after birth. The Developmental Screening Test score of 36 newborns with HIE within 6 months after birth showed that 65% of infants with moderate and high HIE had an abnormal developmental quotient. Conclusion: These data suggest that early measurement of both S100B level and lactate/creatinine ratio in the urine of newborns with HIE is a practical convenient and sensitive way to improve diagnosis on the third day of life and prognostic prediction of HIE.

Application of comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry method to identify potential biomarkers of perinatal asphyxia in a non-human primate model

“…Eight of these metabolites are novel markers of perinatal asphyxia (Tables 2 and 3). Lactate and creatinine are currently the two primary metabolites used clinically to assess the degree of hypoxic-ischemic injury due to perinatal asphyxia [43]. Our findings are consistent with the existing literature for these two compounds, and add novel biomarkers that may be clinically important.…”

Secretoneurin Serum Levels in Healthy Term Neonates and Neonates with Hypoxic-Ischaemic Encephalopathy

“…Of importance, many of these markers were investigated before the introduction of therapeutic hypothermia [24,25]. At present we still lack a biomarker that could early identify infants at risk for brain injury, especially those with mild or moderate HIE.…”

The S100B protein in biological fluids: more than a lifelong biomarker of brain distress

“…The measurement of S100B levels in urine has also been used in perinatal medicine as a means to obtain a noninvasive diagnostic tool. Thus, urine S100B concentrations have been shown to be correlated with gestational age in healthy preterm and term newborns (Gazzolo et al 2001c), and urine S100B concentrations at birth have been shown to be significantly higher in preterm newborns developing IVH and/or brain damage (Gazzolo et al 2001b(Gazzolo et al , 2003dLiu et al 2010). They have also been shown to be a valuable predictor of early neonatal death in preterm and full-term asphyxiated newborns (Gazzolo et al 2005a(Gazzolo et al , 2009.…”