Angelica Dessì

Metabolomics in newborns with intrauterine growth retardation (IUGR): urine reveals markers of metabolic syndrome

To date, we have little knowledge on the overall metabolic status of neonates with intrauterine growth retardation (IUGR). In the last few years, the analysis of metabolomics has assumed an important clinical role in identifying “disorders” in the metabolic profile of patients. The aim of this work has been to analyze the urine metabolic profiles of neonates with IUGR and compare them with controls to define the metabolic patterns associated with this pathology. To our knowledge, this is the first study of metabolomics performed on neonates with IUGR. Recruited for the study were 26 neonates with IUGR diagnosed in the neonatal period and with weight at birth below the 10th percentile and 30 neonates of proper gestational weight at birth (controls). In the first 24 hours (prior to feeding) (T1) and about 4 days after birth (T2), a urine sample was taken non-invasively from each neonate. The samples were then frozen at −80°C up to the time of the analysis by proton nuclear magnetic resonance spectroscopy (1H-NMR). The data contained in the NMR spectra obtained from the single samples were statistically analyzed using the Principal Components Analysis and the Partial Least Squares-Discriminate Analysis. By means of a multivariate analysis of the NMR spectra obtained, it was possible to highlight the differences between the two groups (IUGRs and controls) owing to the presence of different metabolic patterns. The discriminants in the urine metabolic profiles derived essentially from significant differences in certain metabolites such as: myo-inositol, sarcosine, creatine and creatinine. The metabolomic analysis showed different urine metabolic profiles between neonates with IUGR and controls and made it possible to identify the molecules responsible for such differences.

Physiopathology of intrauterine growth retardation: from classic data to metabolomics

It is well know that adverse conditions during intrauterine life, such as intrauterine growth restriction (IUGR), can result in permanent changes in the physiology and metabolism of the newborn, which in turn leads to an increased risk of disease in adulthood (fetal origin of adult disease hypothesis). In the first part of this review the epidemiological studies in which a correlation between low birth weight and chronic pathologies in adulthood was observed are reported. The second part of the review is focused on metabolomics studies that have revealed an altered metabolism in IUGR patients compared to controls. Together with more classic biomarkers of IUGR, such as endothelin-1, leptin, protein S100B and visfatin, the new holistic metabolomics approach has assumed a crescent role in the identification of disorders in the neonatal metabolic profile, determined by the interconnection of the different processes.

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).

Drug treatments in a neonatal setting: focus on the off-label use in the first month of life

Objective The purpose of this work was to analyse drugs prescribed in the first month of life among a group of newborns admitted to the Neonatal Intensive Care Unit and Neonatal Pathology of Cagliari University Hospital. Method This pilot study was prospectively conducted during a 1-month period and involved all newborns admitted to our hospital that received a pharmacotherapy. After obtaining written parental consent, data collected from each newborn included date of birth, sex, gestational age and weight. Also, diagnosis and information about each drug administered during the first month of life: dose, frequency, route of administration, and indication for use was collected. Results Among the 79 newborn infants admitted to our hospital during the study period, 38 received a pharmacotherapy and were enrolled in our study. A total of 88 treatments were given: 41 (47%) followed the terms of the product license, 47 (53%) were used in an unlicensed or off-label manner. Conclusion Our results confirm this trend of drug use in the neonatological field and suggest the need to update information contained in the data sheets of medicines.

Osteo-Articular Infections in Newborns: Diagnosis and Treatment

Abstract Osteoarticular infections, although uncommon, represent a severe condition in neonates. Infections in newborns are largely of an acute nature, transmitted by hematogenous means. The most frequently observed etiological agents are: Staphylococcus aureus, Gram negative and group B Streptococcus spp. In the majority of acases the metaphyses of the long bone are the most commonly implicated sites, although infection may spread to the contiguous epiphysis and joint in neonates. Diagnosis of acute septic arthritis and osteomyelitis may be hindered, especially in neonates, due to the manifestation of less clear-cut characteristic symptoms and signs compared to in children. When osteomyelitis is suspected, imaging techniques used in association with blood and tissue cultures are the most reliable diagnostic tests. Antimicrobial treatment should be administered for 3-4 weeks, initially intravenously, later switching to oral medication. Surgery is indicated to drain acute abscesses or when no improvement is achieved following antibiotic treatment.

Soluble CD14 subtype (sCD14-ST) presepsin in critically ill preterm newborns: preliminary reference ranges

Soluble CD14 subtype (sCD14-ST), also named presepsin, is a 13 kDa truncated form of soluble CD14 (sCD14), consisting of 64 amino acid residues. Systemic inflammation and sepsis are characterized by an early, significant increase in sCD14-ST presepsin blood concentration and thus, this small polypeptide has been proposed as a novel, reliable biomarker for the management of sepsis. We enrolled twenty-six consecutive non-septic preterm newborns with gestational age (GA) between 26 and 36 weeks) admitted to NICU after the first day of life for various severe diseases. sCD14-ST presepsin was measure on whole blood samples by a rapid commercial available chemiluminescent enzyme immunoassay (CLEIA) based on a non-competitive CLEIA. The mean sCD14-ST presepsin blood level in 26 preterm newborns was 643.1 ng/L, with a standard deviation (SD) of 303.8 ng/L; the median value was 578 ng/L. Our results clearly suggest no correlation between GA and sCD14-ST presepsin blood level between 26 and 36 weeks and thus it is reasonable to adopt a unique reference range for preterm newborns.

Serratia marcescens infections and outbreaks in Neonatal intensive Care Units.

Abstract Serratia marcescensis an important cause of hospital-acquired infections, especially in neonatal intensive care units (NICUs). this review analyzes clinical signs, risk factors, biotyping and sources of infection in newborns exhibited by this bacteria as well as the therapy which is commonly used and management. This review examines the reported cases of outbreaks of S. marcescensin NiCUs published in pubmed over the last 10 years. This report highlights the different prevention and control strategies employed in order to eradicate Serratia out breaks in NICUs, including all healthcare procedures such as hand washing, introduction of alcohol-based antiseptic gel, enhanced cleaning and disinfection of medical equipment and wards, use of single-patient medical instruments, cohorting of colonized and infected infants, periodic screening cultures, earliest discharge of the infants.

Clinical impact of human breast milk metabolomics.

Metabolomics is a research field concerned with the analysis of metabolome, the complete set of metabolites in a given cell, tissue, or biological sample. Being able to provide a molecular snapshot of biological systems, metabolomics has emerged as a functional methodology in a wide range of research areas such as toxicology, pharmacology, food technology, nutrition, microbial biotechnology, systems biology, and plant biotechnology. In this review, we emphasize the applications of metabolomics in investigating the human breast milk (HBM) metabolome. HBM is the recommended source of nutrition for infants since it contains the optimal balance of nutrients for developing babies, and it provides a range of benefits for growth, immunity, and development. The molecular mechanisms beyond the inter- and intra-variability of HBM that make its composition unique are yet to be well-characterized. Although still in its infancy, the study of HBM metabolome has already proven itself to be of great value in providing insights into this biochemical variability in relation to mother phenotype, diet, disease, and lifestyle. The results of these investigations lay the foundation for further developments useful to identify normal and aberrant biochemical changes as well as to develop strategies to promote healthy infant feeding practices.

Metabolomics and the great obstetrical syndromes - GDM, PET, and IUGR

Gestational diabetes mellitus, intrauterine growth restriction, and preeclamptic toxemia are common pregnancy complications that can have detrimental effects on morbidity and mortality of the mother and fetus as well as long-term health outcomes. Although they are distinct conditions, they may occur together and are often considered together as they share a common etiology of inadequate placental perfusion. The discovery and study of preventative treatments is hampered by a lack of effective screening tools to accurately identify women at the highest risk of disease. Metabolomics, an omic science, is the global quantitative assessment of endogenous metabolites within a biological system. It has proven to be a rapid approach in the identification of biomarkers predictive of the outcome of a pathological condition and the individuals response to a pharmacological treatment. We review the current and potential applications of metabolomics in maternal-fetal medicine, focusing on its use as a biomarker for great obstetrical syndromes diagnosis.

New diagnostic possibilities in systemic neonatal infections: metabolomics

Systemic neonatal infection is a serious complication in preterm and term infants and is defined as a complex clinical syndrome caused by bacteria, fungi and virus. Sepsis remains among the leading causes of death in both developed and underdeveloped countries above all in the neonatal period. Earlier diagnosis may offer the ability to initiate treatment to prevent adverse outcomes. There have been many studies on various diagnostic haematological markers like acute phase reactants, C-reactive protein, procalcitonin, interleukins and presepsin. However, there is still no single test that satisfies the criteria as being the ideal marker for the early diagnosis of neonatal sepsis. In this regard, metabolomic analysis seems to be a promising method for determining metabolic variations correlated with systemic neonatal infections.