Burnout in doctors and nurses working in neonatal and pediatric intensive care units in a General Hospital

Aim: Health professionals working in intensive care units (ICU) are at high risk of developing the syndrome of professional burnout. The aim of the study was to explore the severity of professional burnout in doctors and nurses of neonatal (NICU) and pediatric ICUs (PICU) while identifying the factors associated with it.Study population and methods: Anonymous questionnaires were distributed to the nurses and doctors working in a NICU and PICU of a General Hospital. We utilized a 22-item questionnaire, the Maslach Burnout Inventory that evaluates three domains of burnout; emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA).Results: The response rate was 58% (52/90). The average (SD) scores were 30.71 (11.5) for EE, 10.11 (5.9) for DP, and 33.37 (8.0) for PA. DP scores were significant higher in PICU than NICU (p = 0.032) and EE and DP scores were higher in nurses than doctors (p 0.013 and p 0.0001 for EE and DP, respectively). Employees who reported health issues had a significantly higher degree of EE (p = 0.044) and appeared less satisfied with their PA (p = 0.046). Multiple regression analysis confirmed that ICU type and professional capacity were independent predictors of burnout. The age, marital status and years of ICU work did not significantly affect the burnout severity.Conclusions: There is a significant degree of burnout in the personnel of Greek PICUs and NICUs which is affected by the professional status, type of ICU, and health issues of the employees involved. The state must implement the necessary interventions that will effectively minimize burnout in ICU personnel in order to prevent the unfavorable consequences on both staff members and inpatients

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. Uni- and multivariate statistical analyses were conducted to evaluate significant metabolites and their prognostic value. Differences in several metabolites were identified between survivors and non-survivors at the time points of the study. Binary logistic regression showed that certain metabolites in gastric fluid, including arabitol, and succinic, erythronic and threonic acids, were associated with 15 DOL and overall survival. Gastric glyceric acid was also associated with 15 DOL survival. Urine glyceric acid could predict survival in the first 3 DOL and overall survival. In conclusion, non-surviving preterm infants exhibited a different metabolic profile compared with survivors, demonstrating significant discrimination with the use of GC-MS-based gastric fluid and urine analyses. The results of this study support the usefulness of metabolomics in developing survival biomarkers in very preterm infants

Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome Associated With a Novel Mutation of FOXP3 Gene

The immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare, x-linked, recessive disorder characterized by dysfunction of the T regulatory (Treg) lymphocytes leading to autoimmune diseases. Herein we report a male patient with IPEX syndrome who presented with severe diarrhea, eczema, and malabsorption leading to failure to thrive and necessitating total parenteral nutrition, as well as with liver dysfunction. Laboratory investigation showed elevated liver enzymes that declined following treatment with glucocorticosteroids and immunosuppressive drugs, marked eosinophilia, increased total IgE, and decreased Treg cells. DNA analysis revealed that the patient himself was hemizygous and his mother heterozygous for the exon 10, c.1015C>T (p.Pro339Ser) mutation of the FOXP3 gene, which has not been previously reported. The current case indicates that mutations resulting in substitution of a certain amino-acid (i.e., proline 339) by different amino-acids are manifested with different IPEX phenotypes

Stressful Newborn Memories: Pre-Conceptual, In Utero, and Postnatal Events

Early-life stressful experiences are critical for plasticity and development, shaping adult neuroendocrine response and future health. Stress response is mediated by the autonomous nervous system and the hypothalamic–pituitary–adrenal (HPA) axis while various environmental stimuli are encoded via epigenetic marks. The stress response system maintains homeostasis by regulating adaptation to the environmental changes. Pre-conceptual and in utero stressors form the fetal epigenetic profile together with the individual genetic profile, providing the background for individual stress response, vulnerability, or resilience. Postnatal and adult stressful experiences may act as the definitive switch. This review addresses the issue of how preconceptual in utero and postnatal events, together with individual differences, shape future stress responses. Putative markers of early-life adverse effects such as prematurity and low birth weight are emphasized, and the epigenetic, mitochondrial, and genomic architecture regulation of such events are discussed

Neonatal carnitine levels and products of intermediary metabolism in relation to maternal carnitine levels in normal and diabetic pregnancy

Carnitine (β-hydroxy-γ-trimethylaminobutyric acid) is an essential cofactor for the transport of long-chain fatty acids across the inner mitochondrial membrane into the mitochondrial matrix, where they are oxidized via β-oxidation. In addition, it is an important regulator in carbohydrate and amino acid metabolism and also buffers potentially toxic acylcoenzyme A (acyl-CoA) metabolites. The sufficiency of free carnitine (FC) and a stable equilibrium between FC and acylcarnitine (AC) are crucial in maintaining adequate carnitine shuttle function. The low carnitine levels in pregnancy reported in previous studies raise concerns regarding the consequences they might have for the mother and the fetus/neonate, especially in pregnancies complicated with gestational diabetes. Theoretically, gestational diabetes is an additional risk factor for carnitine insufficiency in pregnancy, since previous studies showed decreased levels of FC in patients with diabetes mellitus. Furthermore, there is no data on the impact of gestational diabetes on the carnitine shuttle of the fetus/neonate, which depends on the carnitine transfer via the placenta. So far, there is only one published study on carnitine levels in the diabetic pregnant women, which reported increased FC levels in gestational diabetes, while there is no study regarding carnitine levels in neonates born to diabetic mothers. Existing data raise questions regarding the impact of low carnitine levels observed in pregnancy on the intermediary metabolism of the mother and the offspring and the potential need for carnitine supplementation. The primary aim of this study was to investigate the carnitine shuttle system in nor-mal pregnancy and gestational diabetes as well as in the offspring, in parallel with the biochemical profile and the levels of total fatty acids and amino acids of the mother and the neonate in order to further explore whether 1. the low carnitine levels are involved in the changes of the fatty acids, carbohydrate and amino acid metabolism observed in normal pregnancy 2. these changes are exacerbated in well controlled gestational diabetes 3. the low maternal levels affect the neonatal carnitine levels 4. the potential changes in neonatal carnitine levels in normal and diabetic pregnancies are associated with altered intrauterine growth and/or intermediary metabolism of lipids, carbohydrates and amino acids in the newborn. The clarification of the role of the carnitine shuttle system in metabolic adaptation of pregnancy, diabetic and non-diabetic, could help make suggestions on the potential benefit and safety of L-carnitine supplementation to both pregnant women and neonates. To this aim, we assessed the levels of carnitine fractions in dried blood spots of diabetic and non-diabetic pregnant women and their neonates as well as in non-pregnant controls with comparable age which were subsequently related to the anthropometric and biochemical parameters and plasma levels of lipids and amino acids. [...]Η καρνιτίνη κατέχει κεντρική θέση στον μεταβολισμό των λιπών και παίζει σημαντικό ρυθμιστικό ρόλο στον μεταβολισμό των υδατανθράκων και αμινοξέων καθώς και στην απομάκρυνση τοξικών προϊόντων του μεταβολισμού. Για την αποτελεσματική λειτουργία του οχήματος καρνιτίνης, πρέπει να υπάρχει επάρκεια ελεύθερης καρνιτίνης (ΕΚ) και ισορροπία μεταξύ ΕΚ και ακυλιωμένης καρνιτίνης (ΑΚ). Προηγούμενες μελέτες ανέφεραν χαμηλά επίπεδα ΕΚ και ποικίλες μεταβολές στα επίπεδα ΑΚ στη φυσιολογική κύηση και δημιούργησαν προβληματισμό για τις συνέπειες που μπορεί να έχουν οι μεταβολές αυτές για τη μητέρα και το έμβρυο/νεογνό. Ο προβληματισμός αυτός απασχολεί ιδιαίτερα σε κυήσεις που συνοδεύονται από μεταβολικό στρες, όπως συμβαίνει στην κύηση που επιπλέκεται από διαβήτη. Θεωρητικά, ο διαβήτης της κύησης ενέχει έναν επιπρόσθετο κίνδυνο εμφάνισης ανεπάρκειας της καρνιτίνης στη μητέρα, καθώς μελέτες σε ασθενείς με διαβήτη ανέφεραν ελαττωμένα επίπεδα ΕΚ, ενώ είναι άγνωστες οι επιπτώσεις του στο όχημα καρνιτίνης του εμβρύου/νεογνού, το οποίο εξαρτάται αποκλειστικά από τη διαπλακουντιακή μεταφορά καρνιτίνης από τη μητέρα του. Μέχρι σήμερα, υπάρχει μόνο μια δημοσιευμένη μελέτη σε κυήσεις με διαβήτη, η οποία ανέφερε αυξημένη ΕΚ, ενώ δεν υπάρχει καμιά σχετική κλινική μελέτη για τα νεογνά διαβητικών μητέρων. Από τα υπάρχοντα δεδομένα προκύπτουν συγκεκριμένα ερωτήματα που αφορούν τη σημασία των χαμηλών επιπέδων καρνιτίνης για τον μεταβολισμό της εγκύου και του νεογνού σε φυσιολογική και διαβητική κύηση και την ενδεχόμενη ανάγκη θεραπείας υποκατάστασης. Ο κύριος σκοπός της μελέτης αυτής ήταν να μελετηθεί το σύστημα καρνιτίνης σε μη διαβητικές έγκυες και σε έγκυες με διαβήτη της κύησης καθώς και στα νεογέννητά τους, παράλληλα με το βιοχημικό προφίλ και τα επίπεδα των λιπαρών οξέων και αμινοξέων της μητέρας και του νεογνού, ώστε να διερευνηθεί: 1. αν τα χαμηλά επίπεδα κσρνιτίνης στην κύηση συνδέονται με τις μεταβολές στον μεταβολισμό των λιπών, υδατανθράκων και αμινοξέων, που παρατηρούνται στη φυσιολογική κύηση 2. αν οι μεταβολές αυτές επιδεινώνονται σε καλά ρυθμιζόμενο διαβήτη της κύησης 3. αν τα χαμηλά επίπεδα καρνιτίνης στη μητέρα επηρεάζουν τα επίπεδα καρνιτίνης στο νεογνό 4. αν ενδεχόμενες μεταβολές καρνιτίνης σε νεογνά φυσιολογικών ή διαβητικών κυήσεων συσχετίζονται με διαταραχές της ενδομήτριας αύξησης ή/και του εν-διάμεσου μεταβολισμού των λιπών, υδατανθράκων και αμινοξέων στο νεογέννητο. Η διερεύνηση του ρόλου του οχήματος καρνιτίνης στη μεταβολική προσαρμογή κατά την κύηση, διαβητική και μη διαβητική, μπορεί να συμβάλει στην εξαγωγή συμπερασμάτων σχετικά με το δυνητικό όφελος ή βλάβη από τη συμπληρωματική χορήγηση L-καρνιτίνης στη μητέρα και το νεογνό. Για τον σκοπό αυτό, μελετήσαμε τα επίπεδα της ελεύθερης καρνιτίνης, της ακυλκαρνιτίνης και των κλασμάτων της σε αποξηραμένη σταγόνα αίματος σε διαβητικές και μη διαβητικές έγκυες και στα νεογέννητά τους, καθώς και σε φυσιολογικές μη έγκυες γυναίκες συγκρίσιμης ηλικίας, και τα συσχετίσαμε με βασικούς ανθρωπομετρικούς δείκτες, καθώς και με το βιοχημικό προφίλ και τα επίπεδα λιπαρών οξέων ορού και αμινοξέων πλάσματος. [...

The Intertemporal Role of Respiratory Support in Improving Neonatal Outcomes: A Narrative Review

Defining improvements in healthcare can be challenging due to the need to assess multiple outcomes and measures. In neonates, although progress in respiratory support has been a key factor in improving survival, the same degree of improvement has not been documented in certain outcomes, such as bronchopulmonary dysplasia. By exploring the evolution of neonatal respiratory care over the last 60 years, this review highlights not only the scientific advances that occurred with the application of invasive mechanical ventilation but also the weakness of the existing knowledge. The contributing role of non-invasive ventilation and less-invasive surfactant administration methods as well as of certain pharmacological therapies is also discussed. Moreover, we analyze the cost–benefit of neonatal care-respiratory support and present future challenges and perspectives

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. They possess antimicrobial, immunomodulating, inflammation-regulating, and tissue-repairing properties. AMPs are expressed as early as the 13th week and increase progressively through gestation. Limited studies are available on AMP expression and levels in the fetus and neonate. Nevertheless, existing evidence supports the role of AMPs in pathogenesis of chorioamnionitis, neonatal sepsis, and NEC, and their association with disease severity. This suggests a potential role of AMPs in diagnosis, prevention, prognosis, and treatment of sepsis and NEC. Herein, we present an overview of the antimicrobial and immunomodulating properties of human AMPs, their sources in the intrauterine environment, fetus, and neonate, and their changes during pre- and post-natal infections and NEC. We also discuss emerging data regarding the potential utility of AMPs in early-life infections, as diagnostic or predictive biomarkers and as therapeutic alternatives or adjuncts to antibiotic therapy considering the increase of antibiotic resistance in neonatal intensive care units

Humoral Immunity against Measles in Mother–Infant Pairs during the First Year of Life in Greece: A Cross-Sectional Study

Measles outbreaks have surfaced in Europe during the last decades. Infants <12 months of age were the most severely affected pediatric population. The aim of this study was to investigate the duration of maternally derived measles antibodies in infants aged 1 to 12 months in relation to maternal humoral immune status and other parameters. In a prospective, cross-sectional cohort study, 124 mother/infant pairs and 63 additional infants were recruited from October 2015 through December 2019. Infants were hospitalized in a university pediatric department of a general hospital. Demographic and epidemiological data were recorded and blood samples were collected from mothers and their infants. Commercially available enzyme-linked immunosorbent assay (ELISA) was used for measuring measles antibodies. Fifty nine percent of mothers had vaccine-induced and 15% infection-acquired measles immunity. Eighty-eight percent and 94% of infants were unprotected by 5 and 10 months of age, respectively. Maternal antibody levels and infant age were significant independent predictors of infants’ antibody levels whereas the method of maternal immunity acquisition, age, and origin [Greek/non-Greek] were not. Our findings suggest that about 90% of infants are susceptible to measles beyond the age of 4 months. To our knowledge, these are the first data from Greece reported under the current community composition and epidemiological conditions

Humoral Immunity against Measles in Mother–Infant Pairs during the First Year of Life in Greece: A Cross-Sectional Study

Measles outbreaks have surfaced in Europe during the last decades. Infants <12 months of age were the most severely affected pediatric population. The aim of this study was to investigate the duration of maternally derived measles antibodies in infants aged 1 to 12 months in relation to maternal humoral immune status and other parameters. In a prospective, cross-sectional cohort study, 124 mother/infant pairs and 63 additional infants were recruited from October 2015 through December 2019. Infants were hospitalized in a university pediatric department of a general hospital. Demographic and epidemiological data were recorded and blood samples were collected from mothers and their infants. Commercially available enzyme-linked immunosorbent assay (ELISA) was used for measuring measles antibodies. Fifty nine percent of mothers had vaccine-induced and 15% infection-acquired measles immunity. Eighty-eight percent and 94% of infants were unprotected by 5 and 10 months of age, respectively. Maternal antibody levels and infant age were significant independent predictors of infants’ antibody levels whereas the method of maternal immunity acquisition, age, and origin [Greek/non-Greek] were not. Our findings suggest that about 90% of infants are susceptible to measles beyond the age of 4 months. To our knowledge, these are the first data from Greece reported under the current community composition and epidemiological conditions