Laura D. Serpero

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

J. Neurochem. (2012) 120, 644–659.

Urinary 1H-NMR and GC-MS metabolomics predicts early and late onset neonatal sepsis

The purpose of this article is to study one of the most significant causes of neonatal morbidity and mortality: neonatal sepsis. This pathology is due to a bacterial or fungal infection acquired during the perinatal period. Neonatal sepsis has been categorized into two groups: early onset if it occurs within 3-6 days and late onset after 4-7 days. Due to the not-specific clinical signs, along with the inaccuracy of available biomarkers, the diagnosis is still a major challenge. In this regard, the use of a combined approach based on both nuclear magnetic resonance ((1)H-NMR) and gas-chromatography-mass spectrometry (GC-MS) techniques, coupled with a multivariate statistical analysis, may help to uncover features of the disease that are still hidden. The objective of our study was to evaluate the capability of the metabolomics approach to identify a potential metabolic profile related to the neonatal septic condition. The study population included 25 neonates (15 males and 10 females): 9 (6 males and 3 females) patients had a diagnosis of sepsis and 16 were healthy controls (9 males and 7 females). This study showed a unique metabolic profile of the patients affected by sepsis compared to non-affected ones with a statistically significant difference between the two groups (p = 0.05).

Next generation biomarkers for brain injury

Abstract In perinatal medicine, there is an emerging interest on the potential usefulness of non-invasive brain biochemical monitoring in infants at risk for brain injury. To date, several biomarkers such as neuro-proteins, calcium binding proteins, oxidative stress markers, vasoactive agents, inflammatory mediators, have been investigated. Results showed that hypoxia insult, under different conditions, triggers a biochemical pathophysiological cascade of events leading to brain damage. In this setting, increased biomarkers concentrations in different biological fluids have been found to correlate with the occurrence of brain damage at short-long term both in preterm and term fetuses/newborns. However, before inclusion of any biomarker in guidelines, USA and European institutions have recently stated a panel of criteria that have to be fulfilled. Therefore, the present review offers an overview of the main biomarkers currently studied in perinatal medicine and their progresses according to institutions’ criteria.

Perinatal asphyxia: Kidney failure does not affect S100B urine concentrations

BACKGROUND S100B protein is a well-established marker of brain damage. Its importance in urine assessment is the convenience of a collection and sampling procedure that can be repeated without risk for the newborn. Since S100B is mainly eliminated by the kidneys and perinatal asphyxia (PA) is often associated with kidney failure we investigated whether S100B release might be kidney-mediated, thereby modifying the proteins reliability as a brain-damage marker. METHODS We examined a cohort of healthy (n=432) and asphyxiated newborns (n=32) in whom kidney function parameters (blood urea and creatinine concentrations and urine gravity) and urine S100B concentrations were assessed in the first hours after birth. Data were analyzed by multiple logistic regression analysis with S100B as independent variable among a variety of clinical and laboratory monitoring parameters. RESULTS S100B urine concentrations were significantly higher (P<0.01) in PA newborns than controls. No significant correlations (P>0.05, for all) between total urine S100B levels and kidney function parameters such as creatinine (r=0.03), urea (r=0.04) and urine gravity (r=0.06) were found. Multiple logistic regression analysis of a series of clinical and laboratory monitoring parameters (odds ratio at sampling: 9.47) with S100B as independent variable showed a positive significant correlation only between S100B levels (P<0.001) and the occurrence of PA. CONCLUSION The present study shows that altered kidney function is not an adverse and/or confounding factor in urine S100B assessment and marks a new step towards the introduction of longitudinal monitoring of brain constituents in clinical practice.

Human milk and formulae: Neurotrophic and new biological factors

Mother milk is widely accepted to be a unique product believed to contain biological factors involved in the regulation of newborn optimal growth including brain when compared to milk-formula milks. In this setting, there is growing evidence that in milk-formula neuro-oxidative stress biomarkers, neurotrophic proteins and calcium binding proteins, known to be involved in a cascade of events leading to brain, cardiac and vascular development/damage, are to date lacking or at a lower concentration than breast milk. Therefore, this review is aimed at offering additional insights to the role in human milk of some selected biomarkers such as: i) neurotrophic factors such as Activin A; ii) Calcium binding protein such as S100B and, iii) heat shock protein known to be involved in oxidative stress response (namely hemeoxygenase-1, HO-1 or Heat shock Protein 32, HSP32).

S100B Protein Maternal and Fetal bloodstreams gradient in Healthy and Small for Gestational Age Pregnancies

BACKGROUND Brain S100B assessment in maternal blood has been proposed as a useful tool for early perinatal brain damage detection. Among potential confounding factors the possibility of a protein gradient between maternal and fetal bloodstreams under pathophysiological conditions is consistent. The present study investigates in healthy and small gestational age fetuses (SGA) whether S100B concentrations differ among fetal and maternal bloodstreams. METHODS We conducted a case-control study in 160 pregnancies (SGA: n=80; healthy: n=80), in which standard monitoring parameters were recorded. S100B was assessed in arterial cord and in maternal blood samples at birth. Eighty non pregnant women (NP), matched for age at sampling, served as controls (1 SGA vs. 1 healthy vs. 1 NP). RESULTS Fetal S100B in SGA and healthy groups was significantly higher (P<0.01) than that detected in the maternal district and in NP women groups, respectively. No differences in proteins gradient between fetal and maternal bloodstreams (P>0.05) were observed between groups. No differences (P>0.05) in fetal S100B have been found between the studied groups. Maternal S100B of SGA and healthy groups was significantly higher (P<0.01) than that detected in NP women. No differences in maternal S100B concentrations (P>0.05) were observed between SGA and control groups. CONCLUSION The present study shows that S100B is pregnancy-dependent with the presence of a proteins gradient between fetal and maternal bloodstreams. The present data suggests that non-invasive fetal brain monitoring is becoming possible in opening a new cue on further investigations on S100B fetal/maternal gradient changes under pathological conditions.

The clinical and diagnostic utility of S100B in preterm newborns.

Preterm birth is still the most important cause of perinatal mortality and morbidity. Follow-up studies showed that the majority of neurological abnormalities during childhood are already present in the first week after birth. In this light, the knowledge of the timing of the insult and/or of the contributing factors is of utmost relevance in order to avoid adverse neurological outcome. Notwithstanding, the considerable advances in perinatal clinical care and monitoring, the early detection of cases at risk for brain damage is still a challenge because, when radiological pictures are still negative, brain damage may be already at a subclinical stage, with symptoms hidden by therapeutic strategies. Thus, it could be very relevant to measure quantitative parameters, such as neuroproteins, able to detect subclinical lesions at a stage when routine brain monitoring procedures are still silent. In the last decade, the assay of the brain-specific protein S100B in different biological fluids proved useful information on brain function and damage in the perinatal period. Therefore, the present study provides an overview of the most recent findings on S100B role as a reliable marker of brain development/damage in preterm high risk fetuses and newborns.

Urine S100 BB and A1B dimers are valuable predictors of adverse outcome in full-term asphyxiated infants

To investigate whether S100A1B and BB dimers are predictors of early perinatal death in newborns with perinatal asphyxia (PA).

Antenatal glucocorticoid treatment affects preterm infants' S100B urine concentration in a dose-dependent manner

BACKGROUND Maternal glucocorticoid (GC) treatment is widely used to prevent lung immaturity in preterm infants. There is growing evidence that GCs may be detrimental to the Central Nervous System (CNS). We investigated whether antenatal GC administration affects CNS function in a dose-dependent manner by measuring urine concentrations of a well-established brain damage marker, S100B. METHODS We conducted a case-control-study in 70 preterm infants (1 GC vs 1 control) whose mothers received a complete GC-course (GC2, n=16), half-course (GC1, n=19), and controls (n=35). At four predetermined time-points, in the first 72 h from birth, we assessed S100B urine concentrations, using a commercially available immunoluminometric assay (Lia-mat Sangtec 100, AB Sangtec Medical, Bromma, Sweden). Data were correlated with primary neonatal outcomes (incidence of respiratory distress syndrome, length of ventilatory support and hospital stay, incidence of intraventricular hemorrhage, adverse 7th day neurological follow-up and neonatal death). RESULTS S100B in GC2 group at all monitoring time-points was significantly lower (P<0.01) than controls and GC1 group, while no differences (P>0.05) were evident between controls and GC1 group. No significant differences (P>0.05) were shown in primary outcomes between half or complete GC-course treated groups. CONCLUSION S100B levels of infants antenatally treated with GCs differed in a dose-dependent manner. Data on primary outcomes suggest that lowering antenatal GC-course may be less detrimental for brain without affecting lung maturation. Further clinical trials are needed to elucidate the low GC-course issue.

The potentials and limitations of neuro-biomarkers as predictors of outcome in neonates with birth asphyxia

Perinatal asphyxia and its complication, hypoxic-ischemic encephalopathy, are still among the major causes of perinatal mortality and morbidity. Despite accurate standard postnatal monitoring procedures, the post-insult period is crucial because at a time when radiologic pictures are still silent, brain damage may already be at a subclinical stage. Against this background, the measurement of quantitative parameters, such as constituents of nervous tissue, that are able to detect subclinical lesions at a stage when routine brain monitoring procedures are still silent, could be particularly useful. Therefore, in the present review we report the potentials and limitations of biomarkers in predicting outcome in neonates complicated by perinatal asphyxia.