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

Gazzolo, Diego; Marinoni, Emanuela; Iorio, Raffaele; Bruschettini, Matteo; Kornacka, Maria; Lituania, Mario; Majewska, U.; Serra, Giovanni; Michetti, Fabrizio

doi:10.1097/01.ccm.0000104116.91462.cd

Cited by 84 publications

(41 citation statements)

References 33 publications

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“…One possibility is that changes in blood-brain barrier permeability as a result of fetal hypoxia itself or increased cerebral perfusion secondary to redistribution of blood flow may promote leakage of the protein from the CNS into the systemic circulation (23,24). Alternatively, S100␤ may be released from the placenta during hypoxemic conditions.…”

Section: Discussionmentioning

confidence: 99%

Acute Hypoxia Increases S100β Protein in Association with Blood Flow Redistribution away from Peripheral Circulations in Fetal Sheep

et al. 2005

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We investigated in fetal sheep during late gestation the effects of acute hypoxemia on fetal plasma S100␤ protein concentrations and how these relate to fetal redistribution of blood flow and acid-base status. Under general anesthesia, five Welsh Mountain sheep fetuses were instrumented with vascular catheters, and transit-time flow transducers were implanted around a femoral artery and an umbilical artery. At least 5 d after surgery, fetuses were subjected to 1 h of normoxia, 0.5 h of hypoxemia, and 1 h of recovery. Hypoxemia induced significant falls in fetal pH a , arterial oxygen pressure, acid-base excess, and [HCO 3 Ϫ ], without alteration to arterial partial pressure of carbon dioxide. An increase in arterial blood pressure, a fall in heart rate, an increase in femoral vascular resistance, and a decrease in umbilical vascular resistance occurred in all fetuses. During hypoxemia, plasma S100␤ increased significantly and remained elevated until the end of the protocol. Within individual fetuses, plasma S100␤ correlated with femoral vascular resistance and pH. In contrast, no relationship was found between S100␤ and umbilical vascular resistance. This study reports for the first time that a controlled period of fetal hypoxemia with associated acidemia leads to persistent elevations in plasma S100␤ concentrations that strongly correlate with hemodynamic changes that are known to occur during fetal blood flow redistribution. These findings open up a new role for changes in fetal S100␤ concentrations as a possible early marker of fetal hypoxia with associated acidemia in perinatal medicine. The S100␤ proteins are members of a multigenic family of calcium-modulated peptides characterized by a helix-loophelix structure. They were first identified as a protein fraction detectable in brain and found to be mostly of low molecular weight of~10,000 Da. They are called S100 because of their solubility in a 100% saturated solution with ammonium sulfate. In the nervous system, the protein is concentrated in glial cells, but it can also be present in specific neuron populations. Its half-life in the circulation is~1 h, and 98% of the protein is excreted in urine (1-3).An elevation in the concentration of S100␤ in biologic fluids, such as cerebrospinal fluid and plasma, has been proposed to be a reliable marker of stress to the CNS (4 -9). During human pregnancy, the concentration of circulating S100␤ is increased in human fetuses with intrauterine growth restriction (IUGR), in particular in those who show redistribution of blood flow toward the brain (10). This is important because redistribution of blood flow away from peripheral circulations is an established cardiovascular defense response to hypoxia and asphyxia in the fetus (11). Michetti and Gazzolo (2) reported that the expression of S100␤ increases in biologic fluids in the fetus during complicated intrauterine conditions, at times when other clinical assessments miss the adverse diagnosis. More recently, it was also reported that infants with moderate and sever...

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Section: Discussionmentioning

confidence: 99%

Acute Hypoxia Increases S100β Protein in Association with Blood Flow Redistribution away from Peripheral Circulations in Fetal Sheep

et al. 2005

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“…In pre-term infants with IVH, concentrations of S100 in blood were elevated before a radiological diagnosis could be made [116] . In IUGR fe-tuses a signifi cant correlation between protein S100 and cerebral hemodynamics was observed [117] while high values of this protein were detected in term infants with asphyxia and hypoxic-ischemic encephalopathy [118] . Signifi cantly higher values of S100 protein have been demonstrated in neonates with moderate and severe hypoxic-ischemic encephalopathy, and moreover, decreasing values were reported in relation to the time and severity of brain insult [119] .…”

Section: Biomarkersmentioning

confidence: 99%

The Timing of Neonatal Brain Damage

Bracci¹,

Perrone²,

Buonocore³

2006

Neonatology

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Although neonatal morbidity and mortality are less than in the past, the risk of pre-natal and neonatal brain damage has not been eliminated. In order to optimize pre-natal, perinatal and neonatal care, it is necessary to detect factors responsible for brain damage and obtain information about their timing. Knowledge of the timing of asphyxia, infections and circulatory abnormalities would enable obstetricians and neonatologists to improve prevention in pre-term and full-term neonates. Cardiotocography has been criticized as being too indirect a sign of fetal condition and as having various technical pitfalls, though its reliability seems to be improved by association with pulse oximetry, fetal blood pH and electrocardiography. Neuroimaging is particularly useful to determine the timing of hypoxic-ischemic brain damage. Cranial ultrasound has been used to determine the type and evolution of brain damage. Magnetic resonance has also been used to detect antenatal, perinatal and neonatal abnormalities and timing on the basis of standardized assessment of brain maturation. Advances in the interpretation of neonatal electroencephalograms have also made this technique useful for determining the timing of brain lesions. Nucleated red blood cell count in cord blood has been recognized as an important indication of the timing of pre-natal hypoxia, and even abnormal lymphocyte and thrombocyte counts may be used to establish pre-natal asphyxia. Cord blood pH and base excess are well-known markers of fetal hypoxia, but are best combined with heart rate and blood pressure. Other markers of fetal and neonatal hypoxia useful for determining the timing of brain damage are assays of lactate and markers of oxidative stress in cord blood and neonatal blood. Cytokines in blood and amniotic fluid may indicate chorioamnionitis or post-natal infections. The determination of activin and protein S100 has also been proposed. Obstetricians and neonatologists can therefore now rely on various methods for monitoring the risk of brain damage in the antenatal and post-natal periods.

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“…The findings of increased S100B concentrations in biological fluids (e.g., cerebrospinal fluid, blood, urine, and amniotic fluid) of adults (5)(6)(7), infants (8,9 ), and fetuses (10 -15 ) after cell injury in the nervous system have supported the use of S100B as a biochemical marker of brain damage (16 ).…”

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confidence: 99%

High Maternal Blood S100B Concentrations in Pregnancies Complicated by Intrauterine Growth Restriction and Intraventricular Hemorrhage

et al. 2006

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Background: Intrauterine growth restriction (IUGR) is associated with perinatal mortality and with neurologic damage from intraventricular hemorrhage (IVH). We investigated whether S100B, a neural protein found in high concentrations after cell injury in the nervous system, is increased in serum of women whose pregnancies are complicated by IUGR and whose newborns develop IVH. We also explored the prognostic accuracy of maternal serum S100B for IVH in the newborn. Methods: We conducted a case-control study of 106 pregnancies complicated by IUGR, including a subgroup (n ‫؍‬ 26) who developed IVH after birth, and 212 unaffected pregnancies matched for gestational age. Ultrasound examination, Doppler velocimetry patterns (in the utero-placental vessels and middle cerebral artery), and maternal blood collection were performed before birth; cerebral ultrasound and neurologic examinations were performed after birth. Results: S100B was higher (P <0.001) in IUGR pregnancies complicated by IVH than in those that were not and in controls. At a cutoff of 0.72 g/L, sensitivity was 100% [95% confidence interval (95% CI), 87%-100%] and specificity was 99.3% (97.5%-99.9%) for prediction of IVH

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

Abstract: 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.

Cited by 84 publications

References 33 publications

Acute Hypoxia Increases S100β Protein in Association with Blood Flow Redistribution away from Peripheral Circulations in Fetal Sheep

Acute Hypoxia Increases S100β Protein in Association with Blood Flow Redistribution away from Peripheral Circulations in Fetal Sheep

The Timing of Neonatal Brain Damage

High Maternal Blood S100B Concentrations in Pregnancies Complicated by Intrauterine Growth Restriction and Intraventricular Hemorrhage

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