Fetal chronic hypoxia does not affect urinary presepsin levels in newborns at birth.

OBJECTIVES: Early sepsis detection and diagnosis still constitutes an open issue since the accuracy of standard-of care parameters is biased by a series of perinatal factors including hypoxia. Therefore, we aimed at investigating the effect of fetal chronic hypoxia insult on urine levels of a promising new marker of sepsis, namely presepsin (P-SEP). METHODS: We conducted a prospective case-control study in 22 cases of early-intrauterine growth restriction (E-IUGR) compared with 22 small-for-gestational-age (SGA) newborns and 66 healthy controls. P-SEP urine samples were collected over the first 72 h from birth. Blood culture and C-reactive protein (CRP) blood levels were measured in E-IUGR and SGA infants. Perinatal standard monitoring parameters and main outcomes were also recorded. RESULTS: No significant urinary P-SEP differences (p>0.05, for all) were observed among studied groups. Moreover, no significant correlations (p>0.05, for both) between urinary P-SEP and blood CRP levels in both E-IUGR and SGA groups (R=0.08; R=0.07, respectively) were observed. CONCLUSIONS: The present results showing the lack of influence of fetal chronic hypoxia on urinary P-SEP levels offer additional data to hypothesize the possible use of urinary P-SEP measurement in neonates in daily clinical practice. Further multicenter prospective data are needed, including infants with early-onset sepsis.

Effect of temperature on presepsin pre-analytical stability in biological fluids of preterm and term newborns.

OBJECTIVES: Thermostability is one of the pre-requisites for the reliability of analytes in clinical practice and biomedical research. Although presepsin represents a promising new biomarker for the early diagnosis of sepsis in newborns, data on its stability under different storage conditions are lacking. We aimed to investigate presepsin thermostability in blood, urine and saliva samples after thawing at 4 predetermined monitoring time-points in a cohort of preterm and term infants. METHODS: We conducted an observational study, where each case served as its own control, in 24 preterm and term infants. Blood, urine and saliva samples were stored at -80 °C for 18 months, and presepsin measured in different biological fluids at thawing (T0), 24 (T1), 48 (T2) and at 72 (T3) hours after thawing. RESULTS: No significant differences (p>0.05, for all) in presepsin levels were observed at T0-T3 in the different biological fluids. Furthermore, no differences at T0-T3 were observed in presepsin levels between blood and saliva fluids, whilst urine levels were significantly higher (p<0.05, for all) than blood and saliva at T0-T3. CONCLUSIONS: Results on presepsin pre-analytical thermo-stability in different biological fluids after long-term refrigeration support the reliability of this biomarker in the diagnosis and monitoring of perinatal sepsis.

Early changes in S100B maternal blood levels can predict fetal intrauterine growth restriction.

OBJECTIVES: Intrauterine growth restriction (IUGR) represents one of the main causes of perinatal mortality and morbidity. Nowadays, IUGR early diagnosis is mandatory in order to limit the occurrence of multiorgan failure, especially the brain. Therefore, we investigated whether longitudinal S100B assessment in maternal blood could be a trustable predictor of IUGR. METHODS: We conducted a prospective study in 480 pregnancies (IUGR: n=40; small for gestational age, SGA: n=40; controls: n=400) in whom S100B was measured at three predetermined monitoring time-points (T1: 8-18 GA; T2: 19-23 GA; T3: 24-28 GA). RESULTS: Lower S100B in IUGR fetuses than SGA and controls (p<0.05, for all) at T1-T3. Receiver operating characteristic curve showed that S100B at T1 was the best predictor of IUGR (sensitivity: 100 %; specificity: 81.4 %) than T2, T3. CONCLUSIONS: The early lower S100B concentration in pregnant women lately complicated by IUGR support the notion that non-invasive early IUGR diagnosis and monitoring is becoming feasible. Results open the way to further studies aimed at diagnosing and monitoring fetal/maternal diseases at earliest time.

Lutein levels in arterial cord blood correlate with neurotrophic calcium binding S100B protein in healthy preterm and term newborns.

BACKGROUND: S100B is an established biomarker of brain development and damage. Lutein (LT) is a naturally occurring xanthophyll carotenoid mainly concentrated in the central nervous system (CNS), but its neurotrophic role is still debated. We investigated whether LT cord blood concentrations correlate with S100B in a cohort of preterm and term healthy newborns. METHODS: We conducted a prospective study on the distribution of LT and S100B in arterial cord blood of healthy preterm (n = 50) and term (n = 50) newborns. RESULTS: S100B and LT showed a pattern of concentration characterized by higher levels (P < 0.01, for all) at 33-36 weeks gestation (GA) followed by a progressive decrease (P < 0.01, for all) from 37 onwards with a dip at term. Both S100B and LT were gender-dependent with significantly (P < 0.01, for all) higher levels in females in preterm and term groups. S100B (R = 0.68; P < 0.001) and LT (R = 0.40; P = 0.005) correlated with GA at sampling. A positive significant correlation (R = 0.87; P < 0.001) between S100B and LT was found. CONCLUSIONS: The present data showing a correlation between S100B and LT supports the notion of a LT trophic role in the CNS. Further investigations in high-risk infants are needed to elucidate LT involvement in the pathophysiological cascade of events leading to CNS development and damage.

Perinatal presepsin assessment: a new sepsis diagnostic tool?

Perinatal sepsis constitutes a medical emergency and is still one of the major causes of mortality and morbidity. The possibility of an early diagnosis of sepsis is still debated and controversial. In particular, clinical symptoms can be hidden by the association of sepsis with other perinatal diseases and/or by therapeutic strategies performed. In this context, there is evidence that the accuracy of standard of care diagnostic parameters (i.e. blood culture, C-reactive protein, procalcitonin) can be biased by additional confounding factors (gestational age, birth-weight, acute-chronic hypoxia). Therefore, the inclusion in clinical daily practice of new biomarkers of sepsis is of utmost importance. Of a panel of biomarkers, Presepsin (P-SEP) plays an important role in the development and response of the immune system and as an early marker of sepsis both in adult and pediatric patients. Therefore, in the present review we aim to offer an overview of the role of P-SEP in the early detection of perinatal sepsis as a trustworthy marker according to actual statements of official international institutions. Future perspectives regard the possibility of a longitudinal non-invasive biological fluids P-SEP assessment thus limiting the sample stress in high risk newborns.

Perinatal asphyxia partly affects presepsin urine levels in non-infected term infants.

OBJECTIVES: Standard of care sepsis biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) can be affected by several perinatal factors, among which perinatal asphyxia (PA) has a significant role. In this light, new early sepsis biomarkers such as presepsin (P-SEP) are needed to enact therapeutic strategies at a stage when clinical and laboratory patterns are still silent or unavailable. We aimed at investigating the potential effects of PA on longitudinal P-SEP urine levels. METHODS: We conducted an observational case-control study in 76 term infants, 38 with PA and 38 controls. Standard clinical, laboratory, radiological monitoring procedures and P-SEP urine measurement were performed at four time-points (first void, 24, 48, 96 h) after birth. RESULTS: Higher (p<0.05) CRP and PCT blood levels at T1-T3 were observed in PA than control infants whilst no differences (p>0.05, for all) at T0 were observed between groups. P-SEP urine levels were higher (p<0.05) in PA at first void and at 24 h while no differences (p>0.05) at 48 and 96 h were observed. No significant correlations were found (p>0.05) between P-SEP and urea (R=0.11) and creatinine (R=0.02) blood levels, respectively. CONCLUSIONS: The present results, showed that PA effects on P-SEP were limited up to the first 24 h following birth in absence of any kidney function bias. Data open the way to further investigations aimed at validating P-SEP assessment in non-invasive biological fluids as a reliable tool for early EOS and LOS detection in high-risk infants.