Vitamin K insufficiency and the prophylaxis strategy in term healthy infants: A multicentre study.

BACKGROUND/AIM: Late vitamin K deficiency bleeding (VKDB) during early infancy is a serious problem worldwide. Vitamin K (VK) deficiency commonly occurs in newborns who are exclusively breastfed. Protein Induced by VK Absence (PIVKA-II) has been identified as an early indicator of subclinical VK deficiency in neonates, surpassing prothrombin time. To assess PIVKA-II levels at 48 h, 1 and 3 months of age in full-term newborns who were exclusively breastfed and received varying VKDB prophylaxis regimens. METHODS: A prospective observational study was conducted in four hospitals, enrolling 105 newborns. PIVKA-II levels were measured using a sandwich-type enzyme-linked immunosorbent assay. RESULTS: At 48 h of age, there was no significant difference in PIVKA-II concentrations between newborns who received intramuscular administration of 1 mg of phylloquinone (VK1) and those who received oral administration of 2 mg of VK1 at birth. At 1 and 3 months of life, infants who received any supplementation regimen between 2 and 14 weeks exhibited significantly lower PIVKA-II concentrations compared to infants who received only 1 mg of intramuscular VK1 at birth. The prophylaxis involving a dose of 1 mg of intramuscular VK1 at birth followed by oral administration of 150 µg/day of VK1 from the 2nd to the 14th week of life showed the lowest PIVKA-II blood concentrations. CONCLUSIONS: Oral supplementation of VK1 after discharge significantly reduced PIVKA-II concentrations in exclusively breastfed term infants. These findings suggest the importance of oral VK1 supplementation in exclusively breastfed infants during their first 3 months of life to avoid the risk of VK insufficiency.

Cardiovascular Implications of microRNAs in Coronavirus Disease 2019.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to be a global challenge due to resulting morbidity and mortality. Cardiovascular (CV) involvement is a crucial complication in coronavirus disease 2019 (COVID-19), and no strategies are available to prevent or specifically address CV events in COVID-19 patients. The identification of molecular partners contributing to CV manifestations in COVID-19 patients is crucial for providing early biomarkers, prognostic predictors, and new therapeutic targets. The current report will focus on the role of microRNAs (miRNAs) in CV complications associated with COVID-19. Indeed, miRNAs have been proposed as valuable biomarkers and predictors of both cardiac and vascular damage occurring in SARS-CoV-2 infection. SIGNIFICANCE STATEMENT: It is essential to identify the molecular mediators of coronavirus disease 2019 (COVID-19) cardiovascular (CV) complications. This report focused on the role of microRNAs in CV complications associated with COVID-19, discussing their potential use as biomarkers, prognostic predictors, and therapeutic targets.

Untargeted lipidomics reveals specific lipid profiles in COVID-19 patients with different severity from Campania region (Italy).

COVID-19 infection evokes various systemic alterations that push patients not only towards severe acute respiratory syndrome but causes an important metabolic dysregulation with following multi-organ alteration and potentially poor outcome. To discover novel potential biomarkers able to predict disease's severity and patient's outcome, in this study we applied untargeted lipidomics, by a reversed phase ultra-high performance liquid chromatography-trapped ion mobility mass spectrometry platform (RP-UHPLC-TIMS-MS), on blood samples collected at hospital admission in an Italian cohort of COVID-19 patients (45 mild, 54 severe, 21 controls). In a subset of patients, we also collected a second blood sample in correspondence of clinical phenotype modification (longitudinal population). Plasma lipid profiles revealed several lipids significantly modified in COVID-19 patients with respect to controls and able to discern between mild and severe clinical phenotype. Severe patients were characterized by a progressive decrease in the levels of LPCs, LPC-Os, PC-Os, and, on the contrary, an increase in overall TGs, PEs, and Ceramides. A machine learning model was built by using both the entire dataset and with a restricted lipid panel dataset, delivering comparable results in predicting severity (AUC= 0.777, CI: 0.639-0.904) and outcome (AUC= 0.789, CI: 0.658-0.910). Finally, re-building the model with 25 longitudinal (t1) samples, this resulted in 21 patients correctly classified. In conclusion, this study highlights specific lipid profiles that could be used monitor the possible trajectory of COVID-19 patients at hospital admission, which could be used in targeted approaches.

Prolonged refrigeration does not alter isoprostanes concentration in human milk.

BACKGROUND: The Academy of Breastfeeding Medicine published a clinical protocol for Human Milk storage, recommending refrigeration at a temperature of 4 °C up to 4 d as the optimal conditions for the safety and bactericidal capacity of Human Milk. However, few studies were conducted to evaluate the change in milk composition during this type of refrigeration storage. AIM: To elucidate some uncertainties regarding the Human Milk composition and prolonged cold storage, we have investigated the effects of storage at 4 °C up to 96 h on an important category of oxidative stress markers: the Isoprostanes (F2-isoprostanes, F4-neuroprostanes and F3-isoprostanes). MATERIAL AND METHOD: The experiment was repeated 3 times to ensure reproducibility of the results. We enrolled 3 donating healthy mothers for each time (total: 9 mothers). Milk was collected with standard extraction methods. Immediately after collection, each Human Milk sample from each mother was pooled and then divided into 5 aliquots. One aliquot (0 h) was immediately frozen at -80 °C until the analysis. The other aliquots (24 h, 48 h, 72 h, 96 h) were stored in a refrigerator at 4 °C respectively for 24, 48, 72 and 96 h, then immediately frozen at -80 °C until the analysis. Milk samples were then used to determine concentration of Isoprostanes in Liquid Chromatography - Mass Spectrometry and Liquid Chromatography - Tandem Mass Spectrometry. RESULTS: Isoprostanes were detectable in all Human Milk samples. There was no significant trend of the concentration of the tested analytes over time. DISCUSSION AND CONCLUSION: This study provides evidence of the presence in human milk of all the tested isoprostanes: in particular, F2-isoprostanes, F4-neuroprostanes and F3-isoprostanes. Refrigeration and storage of fresh Human Milk in controlled conditions for 96 h did not significantly affect its bioactivity and nutritional quality related with these biomarkers.

Antioxidant Effect of Melatonin in Preterm Newborns.

INTRODUCTION: Preterm infants are at risk of free radical-mediated diseases from oxidative stress (OS) injury. Increased free radical generation has been demonstrated in preterm infants during the first seven days of life. Melatonin (MEL) is a powerful antioxidant and scavenger of free radicals. In preterm neonates, melatonin deficiency has been reported. Exogenous melatonin administration appears a promising strategy in the treatment of neonatal morbidities in which OS has a leading role. OBJECTIVE: The aim was to evaluate plasma MEL concentrations and OS biomarkers in preterm newborns after early administration of melatonin. METHODS: A prospective, randomized double-blind placebo-controlled pilot study was conducted from January 2019 to September 2020. Thirty-six preterm newborns were enrolled. Starting from the first day of life, 21 received a single dose of oral melatonin 0.5 mg/kg once a day, in the morning (MEL group); 15 newborns received an equivalent dose of placebo (placebo group). Samples of 0.2 mL of plasma were collected at 24 and 48 hours after MEL administration. Plasma concentrations of melatonin, non-protein-bound iron (NPBI), advanced oxidation protein products (AOPP), and F2-isoprostanes (F2-Isopr) were measured. Babies were clinically followed until discharge. RESULTS: At 24 and 48 hours after MEL administration, the MEL concentrations were significantly higher in the MEL group than in the placebo group (52759.30 ± 63529.09 vs. 28.57 ± 46.24 pg/mL and 279397.6 ± 516344.2 vs. 38.50 ± 44.01 pg/mL, respectively). NPBI and AOPP did not show any statistically significant differences between the groups both at 24 and 48 hours. At 48 hours, the mean blood concentrations of F2-Isopr were significantly lower in the MEL group than in the placebo group (36.48 ± 33.85 pg/mL vs.89.97 ± 52.01 pg/mL). CONCLUSIONS: Early melatonin administration in preterm newborns reduces lipid peroxidation in the first days of life showing a potential role to protect high-risk newborns. Trial Registration. This trial is registered with NCT04785183, Early Supplementation of Melatonin in Preterm Newborns: the Effects on Oxidative Stress.

Metabolomic Profile of Young Adults Born Preterm.

Prematurity is a risk factor for the development of chronic adult diseases. Metabolomics can correlate the biochemical changes to a determined phenotype, obtaining real information about the state of health of a subject at that precise moment. Significative differences in the metabolomic profile of preterm newborns compared to those born at term have been already identified at birth. An observational case-control study was performed at the University Hospital of Siena. The aim was to evaluate and compare the metabolomic profiles of young adults born preterm to those born at term. Urinary samples were collected from 67 young adults (18-23 years old) born preterm (mean gestational age of 30 weeks, n = 49), and at term of pregnancy (mean gestational age of 38 weeks, n = 18). The urinary spectra of young adults born preterm was different from those born at term and resembled what was previously described at birth. The Random Forest algorithm gave the best classification (accuracy 82%) and indicated the following metabolites as responsible for the classification: citrate, CH2 creatinine, fumarate and hippurate. Urine spectra are promising tools for the early identification of neonates at risk of disease in adulthood and may provide insight into the pathogenesis and effects of fetal programming and infants' outcomes.

Newborn metabolomic profile mirrors that of mother in pregnancy.

BACKGROUND: Pregnancy is characterized by multiple metabolic processes to allow proper foetal development and ensure adequate stores. Little is known about the interactions between maternal and foetal metabolism during the last phase of pregnancy. Metabolomic offers potential to discover changes in maternal metabolism in pregnancy and their relation to the newborn metabolic status. OBJECTIVE: In this study we tested the hypothesis that metabolomic status in newborns at birth depends upon the metabolomic profile of their mothers in the last phase of pregnancy. STUDY DESIGN: Urine samples were collected from 36 pregnant women three weeks before delivery and from 21 healthy term newborns within 48 h after birth. Urines were analysed using proton nuclear magnetic resonance (1H NMR) spectroscopy and NMR urine spectra were evaluated through Principal Components Analysis. RESULTS: The first component of the PCA analysis showed two distinct metabolic groups: pregnant women and newborns. A significant correlation was found between urine metabolic profiles of newborns and those of their mothers. CONCLUSION: Urine metabolomic profiles of newborns at birth mirrors that of their mothers in the last phase of pregnancy. The metabolomic approach appears to be crucial to understand the maternal effects on foetal programming and infant outcomes.