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.

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.

Elevated S100B urine levels predict seizures in infants complicated by perinatal asphyxia and undergoing therapeutic hypothermia.

OBJECTIVES: Seizures (SZ) are one of the main complications occurring in infants undergoing therapeutic hypothermia (TH) due to perinatal asphyxia (PA) and hypoxic ischemic encephalopathy (HIE). Phenobarbital (PB) is the first-line therapeutic strategy, although data on its potential side-effects need elucidation. We investigated whether: i) PB administration in PA-HIE TH-treated infants affects S100B urine levels, and ii) S100B could be a reliable early predictor of SZ. METHODS: We performed a prospective case-control study in 88 PA-HIE TH infants, complicated (n=44) or not (n=44) by SZ requiring PB treatment. S100B urine levels were measured at 11 predetermined monitoring time-points from first void up to 96-h from birth. Standard-of-care monitoring parameters were also recorded. RESULTS: S100B significantly increased in the first 24-h independently from HIE severity in the cases who later developed SZ and requested PB treatment. ROC curve analysis showed that S100B, as SZ predictor, at a cut-off of 2.78 µg/L achieved a sensitivity/specificity of 63 and 84 %, positive/negative predictive values of 83 and 64 %. CONCLUSIONS: The present results offer additional support to the usefulness of S100B as a trustable diagnostic tool in the clinical daily monitoring of therapeutic and pharmacological procedures in infants complicated by PA-HIE.

Cerebral and systemic near infrared spectroscopy patterns in preterm infants treated by caffeine.

AIM: To investigate the effects of caffeine loading/maintenance administration on near-infrared spectroscopy cerebral, kidney and splanchnic patterns in preterm infants. METHODS: We conducted a multicentre case-control prospective study in 40 preterm infants (gestational age 29 ± 2 weeks) where each case acted as its own control. A caffeine loading dose of 20 mg/kg and a maintenance dose of 5 mg/kg after 24 h were administered intravenously. Near infrared spectroscopy monitoring parameters were monitored 30 min before, 30 min during and 180 min after caffeine therapy administration. RESULTS: A significant increase (p < 0.05) in splanchnic regional oxygenation and tissue function and a decrease (p < 0.05) in cerebral tissue function after loading dose was shown. A preferential hemodynamic redistribution from cerebral to splanchnic bloodstream was also observed. After caffeine maintenance dose regional oxygenation did not change in the monitored districts, while tissue function increased in kidney and splanchnic bloodstream. CONCLUSION: Different caffeine administration modalities affect cerebral/systemic oxygenation status, tissue function and hemodynamic pattern in preterm infants. Future studies correlating near infrared spectroscopy parameters and caffeine therapy are needed to determine the short/long-term effect of caffeine in preterm infants.

Circadian Gene Variants: Effects in Overweight and Obese Pregnant Women.

Obesity and overweight are common and complex conditions influenced by multiple genetic and environmental factors. Several genetic variants located in the genes involved in clock systems and fat taste perception can affect metabolic health. In particular, the polymorphisms in CLOCK and BMAL1 genes were reported to be significantly related to cardiovascular disease, metabolic syndrome, sleep reduction, and evening preference. Moreover, genetic variants in the CD36 gene have been shown to be involved in lipid metabolism, regulation of fat intake, and body weight regulation. The aim of this study is to evaluate, for the first time, the association between variants in some candidate genes (namely, BMAL1 rs7950226 (G>A), CLOCK rs1801260 (A>G), CLOCK rs4864548 (G>A), CLOCK rs3736544 (G>A), CD36 rs1984112 (A>G), CD36 rs1761667 (G>A)) and overweight/obesity (OB) in pregnant women. A total of 163 normal-weight (NW) and 128 OB participants were included. A significant correlation was observed between A-allele in CLOCK rs4864548 and an increased risk of obesity (OR: 1.97; 95% CI 1.22-3.10, p = 0.005). In addition, we found that subjects carrying the haplotype of rs1801260-A, rs4864548-A, and rs3736544-G are likely to be overweight or obese (OR 1.47, 95% CI 1.03-2.09, p = 0.030), compared with those with other haplotypes. Moreover, a significant relation was observed between third-trimester lipid parameters and genetic variants-namely, CD36 rs1984112, CD36 rs1761667, BMAL1 rs7950226, and CLOCK rs1801260. A multivariate logistic regression model revealed that CLOCK rs4864548 A-allele carriage was a strong risk factor for obesity (OR 2.05, 95% CI 1.07-3.93, p = 0.029); on the other hand, greater adherence to Mediterranean diet (OR 0.80, 95% CI 0.65-0.98, p = 0.038) and higher HDL levels (OR 0.96, 95% CI 0.94-0.99, p = 0.021) were related to a reduced risk of obesity. Interestingly, an association between maternal CLOCK rs4864548 and neonatal birthweight was detected (p = 0.025). These data suggest a potential role of the polymorphisms in clock systems and in fat taste perception in both susceptibility to overweight/obesity and influencing the related metabolic traits in pregnant women.

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.

S100B in cardiac surgery brain monitoring: friend or foe?

Recent advances in perioperative management of adult and pediatric patients requiring open heart surgery (OHS) and cardiopulmonary bypass (CPB) for cardiac and/or congenital heart diseases repair allowed a significant reduction in the mortality rate. Conversely morbidity rate pattern has a flat trend. Perioperative period is crucial since OHS and CPB are widely accepted as a deliberate hypoxic-ischemic reperfusion damage representing the cost to pay at a time when standard of care monitoring procedures can be silent or unavailable. In this respect, the measurement of neuro-biomarkers (NB), able to detect at early stage perioperative brain damage could be especially useful. In the last decade, among a series of NB, S100B protein has been investigated. After the first promising results, supporting the usefulness of the protein as predictor of short/long term adverse neurological outcome, the protein has been progressively abandoned due to a series of limitations. In the present review we offer an up-dated overview of the main S100B pros and cons in the peri-operative monitoring of adult and pediatric patients.

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.

Early predictors of abnormal MRI patterns in asphyxiated infants: S100B protein urine levels.

OBJECTIVES: The early detection and stratification of asphyxiated infants at higher risk for impaired neurodevelopment is challenging. S100B protein is a well-established biomarker of brain damage, but lacks conclusive validation according to the "gold standard" methodology for hypoxic-ischemic encephalopathy (HIE) prognostication, i.e. brain MRI. The aim of the present study was to investigate the predictive role of urinary S100B concentrations, assessed in a cohort of HIE infants receiving therapeutic hypothermia (TH), compared to brain MRI. METHODS: Assessment of urine S100B concentrations was performed by immunoluminometric assay at first void and at 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120-h after birth. Neurologic evaluation, routine laboratory parameters, amplitude-integrated electroencephalography, and cerebral ultrasound were performed according to standard protocols. Brain MRI was performed at 7-10 days of life. RESULTS: Overall, 74 HIE neonates receiving TH were included in the study. S100B correlated, already at first void, with the MRI patterns with higher concentrations in infants with the most severe MRI lesions. CONCLUSIONS: High S100B urine levels soon after birth constitute trustable predictors of brain injury as confirmed by MRI. Results support the reliability of S100B in clinical daily practice and open the way to its inclusion in the panel of parameters used for the selection of cases suitable for TH treatment.

Different Settings of Nonsynchronized Bilevel Nasal Continuous Positive Airway Pressure and Respiratory Function in Preterm Infants: A Pilot Study.

OBJECTIVE: With this study, we evaluated the short-term effects of different modes and settings of noninvasive respiratory support on gas exchange, breathing parameters, and thoracoabdominal synchrony in preterm infants in the acute phase of moderate respiratory distress syndrome. STUDY DESIGN: A feasibility crossover trial was conducted in neonates < 32 weeks' gestation on nasal continuous positive airway pressure (n-CPAP) or bilevel n-CPAP. Infants were delivered the following settings in consecutive order for 10 minutes each: • n-CPAP (5 cm H2O) • bilevel n-CPAP 1 (Pres low = 5 cm H2O, Pres high = 7 cm H2O, T-high = 1 second, rate = 30/min) • n-CPAP (5 cm H2O) • bilevel n-CPAP 2 (Pres low = 5 cm H2O, Pres high = 7 cm H2O, T-high = 2 second, rate = 15/min) • n-CPAP (5 cm H2O). During each phase, physiologic parameters were recorded; the thoracoabdominal synchrony expressed by the phase angle (Φ) and other respiratory patterns were monitored by noncalibrated respiratory inductance plethysmography. RESULTS: Fourteen preterm infants were analyzed. The mean CPAP level was significantly lower in the n-CPAP period compared with bilevel n-CPAP 1 and 2 (p = 0.03). Higher values were achieved with bilevel n-CPAP 2 (6.2 ± 0.6 vs. 5.7 ± 0.5 cm H2O, respectively; p < 0.05). No statistical difference in the Φ was detected, nor between the three settings. CONCLUSION: Our study did not show any superiority of bilevel n-CPAP over n-CPAP. However, nonsynchronized bilevel n-CPAP might be helpful when additional pressure is needed. KEY POINTS: · There is currently a high degree of uncertainty about the superiority of one modality and setting of noninvasive respiratory over another.. · Our study confirmed that non-synchronized bilevel n-CPAP might be helpful when additional pressure is needed for recruitment.. · A T-high of 1 second could possibly be better tolerated in this population, but further research is needed..

Effect on splanchnic oxygenation of breast milk, fortified breast milk, and formula milk in preterm infants.

BACKGROUND: Enteral feeding induces mesenteric hemodynamic changes in preterm infants, which may vary according to the milk used. Our aim in this study was to evaluate changes of splanchnic regional oxygenation (rSO2S) measured by near-infrared spectroscopy (NIRS) in infants fed with mother's own milk (MOM), fortified human milk (FHM), or preterm formula (PTF). METHODS: Infants born at 25-31 weeks of gestational age (n = 54) received a bolus of MOM, FHM, or PTF. rSO2S and splanchnic fractional oxygen extraction ratio (FOES) were recorded 60 min before (T0), and 30 min (T1) and 120 min (T2) after the beginning of bolus feeding. RESULTS: In the MOM group, rSO2S and FOES did not change during the study period. In the FBM group, rSO2S decreased from T0 to T1 and increased from T1 to T2, while FOES changed in reverse. In the PTF group, rSO2S decreased from T0 to T1 and from T1 to T2, while FOES changed in reverse. CONCLUSIONS: Splanchnic oxygenation was not affected by MOM feeding, was transiently decreased by FBM feeding, and was persistently decreased by PTF. These results suggest that preterm infants who received PTF has higher splanchnic tissue oxygen extraction compared to those who received MOM or FBM. IMPACT: Human milk feeding is associated to a lower splanchnic energy expenditure than preterm formula feeding. Fortified human milk transiently increases splanchnic energy expenditure. Preterm formula should be used only in the absence of human milk.

S100B protein, cerebral ultrasound and magnetic resonance imaging patterns in brain injured preterm infants.

OBJECTIVES: The early detection of preterm infants (PI) at risk for intraventricular hemorrhage (IVH) and neurological sequelae still constitutes an unsolved issue. We aimed at validating the role of S100B protein in the early diagnosis and prognosis of IVH in PI by means of cerebral ultrasound (CUS) and magnetic resonance imaging (MRI) today considered standard of care procedures. METHODS: We conducted an observational case-control study in 216 PI of whom 36 with IVH and 180 controls. Standard clinical, laboratory, radiological monitoring procedures and S100B urine measurement were performed at four time-points (first void, 24, 48, 96 h) after birth. Cerebral MRI was performed at 40-42 weeks of corrected gestational age. RESULTS: Elevated (p<0.001, for all) S100B levels were observed in the IVH group at all monitoring time-point particularly at first void when standard monitoring procedures were still silent or unavailable. S100B measured at first void correlated (p<0.001) with the grade of hemorrhage by means of CUS and with the site and extension of neurological lesion (p<0.001, for all) as assessed by MRI. CONCLUSIONS: The present results showing a correlation among S100B and CUS and MRI offer additional support to the inclusion of the protein in clinical daily management of cases at risk for IVH and adverse neurological outcome. The findings open the way to further investigations in PI aimed at validating new neurobiomarkers by means of S100B.

Heart rate variability as possible marker of brain damage in neonates with hypoxic ischemic encephalopathy: a systematic review.

Heart rate variability (HRV) is currently considered the most valuable non-invasive test to investigate the autonomic nervous system function, based on the fact that fast fluctuations might specifically reflect changes of sympathetic and vagal activity. An association between abnormal values of HRV and brain impairment has been reported in the perinatal period, although data are still fragmentary. Considering such association, HRV has been suggested as a possible marker of brain damage also in case of hypoxic-ischemic encephalopathy following perinatal asphyxia. The aim of the present manuscript was to review systematically the current knowledge about the use of HRV as marker of cerebral injury in neonates suffering from hypoxic-ischemic encephalopathy. Findings reported in this paper were based on qualitative analysis of the reviewed data. Conclusion: A growing body of research supports the use of HRV as non-invasive, bedside tool for the monitoring of hypoxic-ischemic encephalopathy. The currently available data about the role of HRV as prognostic tool in case of hypoxic ischemic encephalopathy are promising but require further validation by future studies. What is Known: • Heart rate variability (HRV) is a non-invasive monitoring technique to assess the autonomic nervous system activity. • A correlation between abnormal HRV and cerebral injury has been reported in the perinatal period, and HRV has been suggested as possible marker of brain damage in case of hypoxic-ischemic encephalopathy. What is New: • HRV might provide precocious information about the entity of brain injury in asphyxiated neonates and be of help to design early, specific, and personalized treatments according to severity. • Further investigations are required to confirm these preliminary data.

Antenatal and Perioperative Mechanisms of Global Neurological Injury in Congenital Heart Disease.

Congenital heart defects (CHD) is one of the most common types of birth defects. Thanks to advances in surgical techniques and intensive care, the majority of children with severe forms of CHD survive into adulthood. However, this increase in survival comes with a cost. CHD survivors have neurological functioning at the bottom of the normal range. A large spectrum of central nervous system dysmaturation leads to the deficits seen in critical CHD. The heart develops early during gestation, and CHD has a profound effect on fetal brain development for the remainder of gestation. Term infants with critical CHD are born with an immature brain, which is highly susceptible to hypoxic-ischemic injuries. Perioperative blood flow disturbances due to the CHD and the use of cardiopulmonary bypass or circulatory arrest during surgery cause additional neurological injuries. Innate patient factors, such as genetic syndromes and preterm birth, and postoperative complications play a larger role in neurological injury than perioperative factors. Strategies to reduce the disability burden in critical CHD survivors are urgently needed.

Early predictors of perinatal brain damage: the role of neurobiomarkers.

The early detection of perinatal brain damage in preterm and term newborns (i.e. intraventricular hemorrhage, periventricular leukomalacia and perinatal asphyxia) still constitute an unsolved issue. To date, despite technological improvement in standard perinatal monitoring procedures, decreasing the incidence of perinatal mortality, the perinatal morbidity pattern has a flat trend. Against this background, the measurement of brain constituents could be particularly useful in the early detection of cases at risk for short-/long-term brain injury. On this scenario, the main European and US international health-care institutions promoted perinatal clinical and experimental neuroprotection research projects aimed at validating and including a panel of biomarkers in the clinical guidelines. Although this is a promising attempt, there are several limitations that do not allow biomarkers to be included in standard monitoring procedures. The main limitations are: (i) the heterogeneity of neurological complications in the perinatal period, (ii) the small cohort sizes, (iii) the lack of multicenter investigations, (iv) the different techniques for neurobiomarkers assessment, (iv) the lack of consensus for the validation of assays in biological fluids such as urine and saliva, and (v), the lack of reference curves according to measurement technique and biological fluid. In the present review we offer an up-to-date overview of the most promising developments in the use of biomarkers in the perinatal period such as calcium binding proteins (S100B protein), vasoactive agents (adrenomedullin), brain biomarkers (activin A, neuron specific enolase, glial fibrillary acidic protein, ubiquitin carboxyl-terminal hydrolase-L1) and oxidative stress markers.

Small-for-gestational-age birth is linked to cardiovascular dysfunction in early childhood.

BACKGROUND: The aim of this study was to assess clinical and echographic markers of cardiovascular dysfunction in infants born small for gestational age (SGA) compared to a control group of subjects born adequate for gestational age (AGA). METHODS: This was a single-center cross-sectional case-control study. We recruited 20 SGA and 20 gestational age-matched AGA subjects at 24 months of age. The study population underwent anthropometric and Doppler 2-dimensional echocardiographic assessments, and carotid artery intima-media thickness (cIMT) and endothelium-dependent vasodilation evaluation (FMD). The pressure-volume curve during diastole was calculated using the algorithm for the elastance calculation on 1 single beat. RESULTS: SGA children showed lower stroke volume, lower left ventricle (LV) dimensions and volume, and greater LV thickness. Diastolic function was impaired in SGA with lower capacitance and higher elastance. Birth weight standard deviation score was positively associated with capacitance and negatively associated with E/E' ratio and elastance, and in SGA infants, the end-diastolic pressure-related volume curve was shifted to the left compared to AGA. cIMT and systemic vascular resistance were significantly higher, while FMD was lower, in SGA compared to AGA; birth weight standard deviation score was directly correlated with FMD and inversely correlated with cIMT. Finally, a longer breastfeeding duration was associated to a lower cIMT even after correction for confounding factors. CONCLUSIONS: This study shows that infants born SGA present an early and subtle cardiovascular dysfunction compared to AGA controls. These alterations are strongly related to weight at birth. Finally, breastfeeding exerts an important protective and beneficial cardiovascular effect.

Monitoring the effectiveness of hypothermia in perinatal asphyxia infants by urinary S100B levels.

Background Perinatal asphyxia is a major cause of mortality and morbidity in neonates: The aim of the present study was to investigate, by means of longitudinal assessment of urinary S100B, the effectiveness of hypothermia, in infants complicated by perinatal asphyxia and hypoxic-ischemic encephalopathy. Methods We performed a retrospective case-control study in 108 asphyxiated infants, admitted to nine tertiary departments for neonatal intensive care from January 2004 to July 2017, of whom 54 underwent hypothermia treatment and 54 did not. The concentrations of S100B protein in urine were measured using an immunoluminometric assay at first urination and 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120 h after birth. The results were correlated with the achievement of S100B levels within normal ranges at 72 h from hypothermia treatment. Routine laboratory parameters, longitudinal cerebral function monitoring, cerebral ultrasound and neurologic patterns were assessed according to standard protocols. Results Higher S100B concentrations were found in hypothermia-treated infants in both moderate (up to 12 h) and severe (up to 24 h) hypoxic-ischemic encephalopathy. S100B levels returned to normal ranges starting from 20 h of hypothermia treatment in moderate and from 36 h in severe hypoxic-ischemic encephalopathy. Conclusions The present results offer additional support to the usefulness of longitudinal neuro-biomarkers monitoring in asphyxiated infants treated by hypothermia. The pattern of S100B concentrations during hypothermia supports the need for further investigations aimed at reconsidering the time-window for patient recruitment and treatment, and the optimal duration of the cooling and rewarming phases of the hypothermia procedure.

NIRS cerebral patterns in healthy late preterm and term infants are gender- and gestational age-dependent.

AIM: Near-infrared spectroscopy (NIRS) has been proposed to provide reliable information concerning brain oximetry and tissue activation level in the perinatal period. We aimed to investigate whether NIRS brain patterns in healthy preterm (PT) and term (T) infants were gender- and gestational age (GA)-dependent. METHODS: We conducted an observational study in 74 newborns, from consecutive singleton pregnancies, of whom 37 were born at term (male: n = 19 female: n = 18) and 37 (male: n = 18 female: n = 19) were PT. Cerebral oximetry (crSO2 ) and fractional tissue oxygen extraction (cFTOE), were recorded on the 5th day from birth. RESULTS: crSO2 was significantly higher and cFTOE lower (p < 0.001, for both) in the PT female than male group. At term, crSO2 was significantly higher and cFTOE lower (p < 0.001, for both) in males. crSO2 (male: R = 0.84, p < 0.001; female: R = 0.74, p < 0.001) and cFTOE (male: R = 0.72, p < 0.001; female: R = 0.72, p < 0.001) in male and female groups correlated positively with GA at recording. CONCLUSION: Different brain oximetry between males and females in PT a T infants, may suggest that in the perinatal period brain development is gender- and time-dependent. Data support the use of NIRS as a feasible tool for non-invasive cerebral monitoring.

Effects of Sustained Inflation or Positive Pressure Ventilation on the Release of Adrenomedullin in Preterm Infants with Respiratory Failure at Birth.

OBJECTIVE: Delivery room (DR) management may play an important role in the development and prevention of lung injury. Therefore, in a cohort of low birth weight infants (LBW), we investigated the effects of two different lung recruitment maneuvers, such as positive pressure ventilation (PPV) and sustained inflation (SI) on adrenomedullin (AM), a well-established lung-specific vasoactive agent. STUDY DESIGN: This is a prospective case-control randomized study in 44 LBW infants spontaneously breathing with respiratory failure at birth requiring respiratory support. LBW were randomized to receive PPV (n = 22) or SI (n = 22) support. AM was measured from blood in samples collected at birth from arterial artery (BLT0) and at 1-hour (BLT1) and at 24-hour (BLT2) from peripheral venous site. AM assessment in urine samples was performed at 1-hour (URT1) and at 24-hour (URT2). RESULTS: No significant differences in AM (p > 0.05) blood (T0-T2) and urine (T1, T2) levels were observed between groups. CONCLUSION: The present data, showing the absence of any differences in AM blood and urine levels, suggest that PPV and SI are both feasible and equally effective DR maneuvers. The findings open the way to further studies evaluating the effects of PPV and SI on short-/long-term respiratory outcome through biomarkers assessment.