Struggling to Understand the NEC Spectrum-Could the Integration of Metabolomics, Clinical-Laboratory Data, and Other Emerging Technologies Help Diagnosis?

Necrotizing enterocolitis (NEC) is the most prevalent and potentially fatal intestinal injury mainly affecting premature infants, with significant long-term consequences for those who survive. This review explores the scale of the problem, highlighting advancements in epidemiology, the understanding of pathophysiology, and improvements in the prediction and diagnosis of this complex, multifactorial, and multifaced disease. Additionally, we focus on the potential role of metabolomics in distinguishing NEC from other conditions, which could allow for an earlier and more accurate classification of intestinal injuries in infants.

Antibiotics, Analgesic Sedatives, and Antiseizure Medications Frequently Used in Critically Ill Neonates: A Narrative Review.

Antibiotic, analgesic sedative, and antiseizure medications are among the most commonly used medications in preterm/sick neonates, who are at high risk of nosocomial infections, central nervous system complications, and are exposed to numerous painful/stressful procedures. These severe and potentially life-threatening complications may have serious short- and long-term consequences and should be prevented and/or promptly treated. The reported variability in the medications used in neonates indicates the lack of adequate neonatal studies regarding their effectiveness and safety.

Antifungal Drug Usage in European Neonatal Units: A Multicenter Weekly Point Prevalence Study.

Background: Data on antifungal prescribing in neonatal patients are limited to either single-center or single-country studies or to 1-day recording. Therefore, we assessed antifungal longitudinal usage in neonatal units (NUs) within Europe.

Methods: CALYPSO, a prospective weekly point prevalence study on antifungal drug usage in NUs in 18 hospitals (8 European countries), was conducted in 2020 during a 12-week period.

An Update on Pharmacologic Management of Neonatal Hypotension: When, Why, and Which Medication.

Anti-hypotensive treatment, which includes dopamine, dobutamine, epinephrine, norepinephrine, milrinone, vasopressin, terlipressin, levosimendan, and glucocorticoids, is a long-established intervention in neonates with arterial hypotension (AH). However, there are still gaps in knowledge and issues that need clarification. The main questions and challenges that neonatologists face relate to the reference ranges of arterial blood pressure in presumably healthy neonates in relation to gestational and postnatal age; the arterial blood pressure level that potentially affects perfusion of critical organs; the incorporation of targeted echocardiography and near-infrared spectroscopy for assessing heart function and cerebral perfusion in clinical practice; the indication, timing, and choice of medication for each individual patient; the limited randomized clinical trials in neonates with sometimes conflicting results; and the sparse data regarding the potential effect of early hypotension or anti-hypotensive medications on long-term neurodevelopment.

Intertemporal Improvement in Physicians' Perceptions of the Short-Term Adverse Outcomes of Neonatal Pain: Results of a Two-Time-Point National Survey.

Pain in early life may seriously impact neonatal outcomes. This study aimed to evaluate whether the perceptions of physicians working in neonatal intensive care units (NICUs) of the short-term adverse outcomes associated with neonatal pain have changed over a 20-year period. Self-administered questionnaires were distributed to 117 and 145 neonatologists, pediatricians, and fellows working in level III NICUs in 2000 (T1) and 2019 (T2), respectively.

Gastric Fluid Metabolomics Predicting the Need for Surfactant Replacement Therapy in Very Preterm Infants Results of a Case-Control Study.

Respiratory distress syndrome (RDS) is a major morbidity of prematurity. In this case-control study, we prospectively evaluated whether untargeted metabolomic analysis (gas chromatography-mass spectrometry) of the gastric fluid could predict the need for surfactant in very preterm neonates. 43 infants with RDS necessitating surfactant (cases) were compared with 30 infants who were not treated with surfactant (controls).

Off-label Use of Ceftazidime/Avibactam in Neonatal Intensive Care Unit: A Real-life Experience and Literature Review.

Background: Multi/extensively drug-resistant bacterial infections have recently increased and new antimicrobial options are needed for difficult-to-treat infections. Ceftazidime/avibactam (CZA) has been approved for patients 3 months to 18 years of age, but real-life data on its off-label use in neonates and young infants are still scarce.

Materials: We report demographic, clinical and microbiologic data as well as outcome and safety of all cases of infants treated with CZA between January 1, 2021 and September 30, 2022 in a tertiary neonatal intensive care unit.

Strong Association between Inotrope Administration and Intraventricular Hemorrhage, Gestational Age, and the Use of Fentanyl in Very Low Gestational Age Infants: A Retrospective Study.

This was a single center, retrospective cohort study designed to evaluate the association between the administration of inotropes to hypotensive very low gestational age infants (VLGAI) and prenatal and neonatal risk factors. Inpatient medical records were reviewed to identify neonates treated with inotropes (treated group) and a control group for comparison. Two hundred and twenty two (222) VLGAI (less than 32 weeks' gestation) were included in the final analysis and were stratified based on timing of treatment with 83 infants (37.

Neonatal Bloodstream Infection with Ceftazidime-Avibactam-Resistant -Producing Carrying .

Background: Although ceftazidime/avibactam (CAZ/AVI) has become an important option for treating adults and children, no data or recommendations exist for neonates. We report a neonatal sepsis case due to CAZ/AVI-resistant -harboring carrying and the use of a customized active surveillance program in conjunction with enhanced infection control measures.

Methods: The index case was an extremely premature neonate hospitalized for 110 days that had been previously treated with multiple antibiotics.

Evaluation of viral concentration and extraction methods for SARS-CoV-2 recovery from wastewater using droplet digital and quantitative RT-PCR.

The ongoing pandemic caused by the emergence of SARS-CoV-2 has resulted in millions of deaths worldwide despite the various measures announced by the authorities. Wastewater-based epidemiology has the ability to provide a day-to-day estimation of the number of infected people in a fast and cost-effective manner. However, owing to the complex nature of wastewater, wastewater monitoring for viral genome copies is affected by the extensive viral fragmentation that takes place all the way to the sewage and the analytical lab.

Use of Newer and Repurposed Antibiotics against Gram-Negative Bacteria in Neonates.

Antimicrobial resistance has become a significant public health problem globally with multidrug resistant Gram negative (MDR-GN) bacteria being the main representatives. The emergence of these pathogens in neonatal settings threatens the well-being of the vulnerable neonatal population given the dearth of safe and effective therapeutic options. Evidence from studies mainly in adults is now available for several novel antimicrobial compounds, such as new β-lactam/β-lactamase inhibitors (e.

A Cohort Study of Gastric Fluid and Urine Metabolomics for the Prediction of Survival in Severe Prematurity.

Predicting survival in very preterm infants is critical in clinical medicine and parent counseling. In this prospective cohort study involving 96 very preterm infants, we evaluated whether the metabolomic analysis of gastric fluid and urine samples obtained shortly after birth could predict survival in the first 3 and 15 days of life (DOL), as well as overall survival up to hospital discharge. Gas chromatography-mass spectrometry (GC-MS) profiling was used.

Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS).

Background: There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design.

Methods And Findings: Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa).

Challenges in the Implementation of the NeoOBS Study, a Global Pragmatic Observational Cohort Study, to Investigate the Aetiology and Management of Neonatal Sepsis in the Hospital Setting.

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis.

Modifiable risk factors associated with later gut decolonization of carbapenem-resistant Gram-negative bacteria in children: a prospective cohort study.

Background: Nosocomial infections caused by carbapenem-resistant Gram-negative bacteria (CRGNB) are associated with increased mortality and prolonged hospitalization; thus, later CRGNB decolonization has significant clinical and public health implications.

Aim: To investigate modifiable/non-modifiable risk factors for CRGNB later gut decolonization in children.

Methods: CRGNB carriers (aged from one day to 16 years) hospitalized in a tertiary level hospital (2018-2019) were included.

Delta SARS-CoV-2 variant is entirely substituted by the omicron variant during the fifth COVID-19 wave in Attica region.

Wastewater analysis is the most attractive alternative way for the quantification and variant profiling of SARS-CoV-2. Infection dynamics can be monitored by RT-qPCR assays while NGS can provide evidence for the presence of existing or new emerging SARS-CoV-2 variants. Herein, apart from the infection dynamic in Attica since June 1st, 2021, the monitoring of 9 mutations of the omicron and 4 mutations of the delta SARS-CoV-2 variants, utilizing both novel Nested-Seq and RT-PCR, is reported and the substitution of the delta variant (B.

A Prospective, Case-Control Study of Serum Metabolomics in Neonates with Late-Onset Sepsis and Necrotizing Enterocolitis.

Late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) are major causes of neonatal morbidity and mortality. In this prospective, case-control study, we evaluated the metabolic profile of neonates with LOS and NEC. Blood samples were collected from 15 septic neonates and 17 neonates with NEC at the clinical suspicion of the specific diseases.

Antimicrobial Peptides in Early-Life Host Defense, Perinatal Infections, and Necrotizing Enterocolitis-An Update.

Host defense against early-life infections such as chorioamnionitis, neonatal sepsis, or necrotizing enterocolitis (NEC) relies primarily on innate immunity, in which antimicrobial peptides (AMPs) play a major role. AMPs that are important for the fetus and neonate include α and β defensins, cathelicidin LL-37, antiproteases (elafin, SLPI), and hepcidin. They can be produced by the fetus or neonate, the placenta, chorioamniotic membranes, recruited neutrophils, and milk-protein ingestion or proteolysis.

Evolution of factors shaping the endoplasmic reticulum.

Endomembrane system compartments are significant elements in virtually all eukaryotic cells, supporting functions including protein synthesis, post-translational modifications and protein/lipid targeting. In terms of membrane area the endoplasmic reticulum (ER) is the largest intracellular organelle, but the origins of proteins defining the organelle and the nature of lineage-specific modifications remain poorly studied. To understand the evolution of factors mediating ER morphology and function we report a comparative genomics analysis of experimentally characterized ER-associated proteins involved in maintaining ER structure.

Systematic Review and Meta-Analysis of Cardiovascular Medications in Neonatal Hypotension.

Background: Comparative studies among the various cardiovascular medications used for the treatment of neonatal hypotension are lacking.

Methods: This systematic review and pairwise meta-analysis of the anti-hypotensive treatments in preterm and term infants was conducted to evaluate efficacy and impact on outcome. Electronic databases were searched up to February 2021 for relevant articles.

Lethal COG6-CDG in neonatal patient with arachnodactyly, joint contractures, and skin manifestations: Founder mutation in the Southeastern European population?

Herein, we report a lethal case of the ultra-rare COG6-congenital disorder of glycosylation (CDG) presenting with skin manifestations (scaling and erosions) and joint contractures in a neonate of Albanian origin. The patient was homozygous for a COG6 pathogenic variant, previously reported in another three individuals of Greek, Bulgarian and Turkish descent. The presence of a founder mutation in the geographical area is possible.

Plasma Lipidomic and Metabolomic Profiling after Birth in Neonates Born to SARS-CoV-19 Infected and Non-Infected Mothers at Delivery: Preliminary Results.

Pregnant women are among the high-risk populations for COVID-19, whereas the risk of vertical transmission to the fetus is very low. Nevertheless, metabolic alternations described in COVID-19 patients may also occur in pregnant women and their offspring. We prospectively evaluated the plasma lipidomic and metabolomic profiles, soon after birth, in neonates born to infected mothers (cases, = 10) and in the offspring of uninfected ones at delivery (controls, = 10).