S100B Protein in Urine of Preterm Newborns with Ominous Outcome

Abstract

Prematurity is an important cause of perinatal death, and no reliable biochemical/biophysical markers exist to identify newborns with an increased mortality risk. We aimed to use S100B concentrations in urine as an early indicator of risk of neonatal death. We did a cross-sectional study using urine obtained from 165 preterm newborns, of whom 11 suffered neonatal death within the first week, 121 displayed no overt neurologic syndrome, and 33 suffered neonatal hypoxia and intraventricular hemorrhage (IVH) but not ominous outcome. Urine S100B concentrations were determined at four time-points and corrected for gestational age by conversion to multiples of median (MoM) of healthy controls of the same gestational age. Ultrasound imaging was assessed within the first 72 h from birth. In infants that died within the first week, S100B levels in urine were already higher than controls at first urination and increased progressively between the 24 and 96-h time-points. Multiple logistic regression analysis showed a significant correlation between urine S100B protein concentrations and the occurrence of neonatal death. An S100B concentration cut-off of 12.93 MoM at first urination had a sensitivity of 100% and a specificity of 97.8% for predicting an ominous outcome. The positive predictive value was 78.6%, the negative predictive value was 100%. Measurement of urine S100B protein levels in preterm newborns could be useful to identify newborns at higher risk of neonatal death. Prematurity constitutes the main cause leading to perinatal death and about 10 -15% of high-risk newborns might have an ominous outcome (1,2). The possibility of early identification of infants at higher risk of death is to date limited, inasmuch as clinical, laboratory and standard monitoring procedures may be of no avail. There is thus a constant need for practical and sensitive markers able to identify patients at higher risk as early as possible, to take immediate preventive or therapeutic measures. The inclusion of such a marker in evidence-based guidelines is eagerly awaited; however, at present no effective biochemical or biophysical tools exist to predict newborns at higher risk of perinatal death (1-4).The presence in blood of elevated concentrations of a brain constituent such as S100B protein has been described as prognostic of death in adults, and it has been suggested that measurement of this protein be included among peri-mortem procedures (5). S100B is an acidic calcium-binding protein of the EF-hand family (6) that is highly concentrated in the nervous system; it has a half-life of about 1 h and is mainly eliminated in urine (7). In this respect, raised urine S100B concentrations are a consolidated marker of brain damage in infants (8 -10) and in preterm newborns with IVH (11), whereas increased amniotic fluid S100B concentrations are a marker of fetal death (12). Because urine is a clinically accessible fluid for the measurement of S100B when monitoring newborns at high risk, we aimed to evaluate whether

Biological and methodological features of the measurement of S100B, a putative marker of brain injury

“…Recently, we evaluated urine S100B by ELISA in children without any history of brain injury or renal impairment [54]. Only 2 out of 13 children did not present detectable urine S100B, indicating the high sensitivity of our immunoassay, however the percentage of detection in urine in children should be examined in a larger sample [81].…”

Diagnostic Accuracy of S100B Urinary Testing at Birth in Full-Term Asphyxiated Newborns to Predict Neonatal Death

“…With regard to perinatal medicine, it is noteworthy that S100B has recently been shown to be a reliable diagnostic test for predicting newborns at risk of pre-perinatal death [13], [14]. Of the biological fluids in which this protein has been assessed, urine appears to be the most suitable, because it can be collected easily and sampling can be repeated without additional risks for the newborn.…”

S100β Protein Expression: Gender- and Age-Related Daily Changes

“…The conspicuous gender difference in S100b expression observed in the forebrain of adult rats finds support by research indicating a higher amount of this protein in the urine, serum or cerebrospinal fluid in evaluations of patients [20,29,30]. However, some measurements of S100b in the same fluids discount gender or age differences [21,23,31].…”