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We present a case of a preterm neonate with a type IV laryngo-tracheo-oesophageal cleft, an uncommon congenital malformation, resulting from the failure of separation of the trachea and the oesophagus during fetal development, often associated with other deformities as well. Data in the literature shows that the long-term morbidity from the entity has declined over the last decades, even though prognosis remains unfavourable for types III and IV. This report emphasizes the complex issues neonatologists are faced with, when treating neonates with this rare disorder in the first days of life, what will raise suspicion of this rare medical entity, and that direct laryngoscopy/bronchoscopy finally depicts the exact extension of the medical condition. At the same time extensive evaluation for coexisting congenital anomalies should be performed. For all the above reasons, these neonates should be treated in specialized tertiary pediatric centers for multidisciplinary prompt management, which may improve, the outcome.

Abstract Background Late-onset neonatal sepsis (LOS) is common in preterm neonates, with increasing incidence in recent years. In the present study, we examined the epidemiology, clinical presentation, and complications of LOS in Cyprus and quantified possible risk factors for the development of this condition. Methods The study subjects were preterm neonates admitted in the Neonatal Intensive Care Unit (NICU) of Archbishop Makarios III Hospital, the only neonatal tertiary centre in Cyprus. A prospective, case-control study was designed, and carried out between April 2017-October 2018. Depending on blood culture results, preterm neonates were classified as “Confirmed LOS”: positive blood culture - microorganism isolated and LOS symptoms, “Unconfirmed LOS”: negative blood culture and LOS symptoms, and “Controls” group: negative blood culture and absence of LOS symptoms. Comparisons between the 3 groups were performed and the associations between demographic, clinical and treatment characteristics with the likelihood of LOS were assessed using univariate and multivariate logistic regression. Results A total of 350 preterm neonates were included in the study and the incidence of LOS was 41.1%. 79 (22.6%) and 65 (18.6%) neonates were classified as “Confirmed LOS”, and “unconfirmed LOS” cases respectively while 206 (58.9%) served as controls. The rate of confirmed LOS ranged from 12.2% in moderate to late preterm neonates to 78.6% in extremely preterm neonates. In the multivariate model, we demonstrated an independent association between LOS and duration of hospitalization (OR: 1.06, 95%CI: 1.01–1.10), duration of ventilation (OR: 1.23, 95%CI: 1.07–1.43) and necrotising enterocolitis (OR: 3.41, 95%CI: 1.13–10.25). Conclusions The present study highlights the epidemiology of LOS in preterm neonates in Cyprus and its association with the duration of ventilation and hospitalization as well as with necrotizing enterocolitis. Establishment of protocols for the prevention of nosocomial infections during hospitalization in the NICUs and mechanical ventilation of preterm neonates is recommended.

Feto-maternal microchimerism is the bidirectional transfer of cells through the placenta during pregnancy that can affect the health of both the mother and the offspring, even in childhood or adulthood. However, microchimerism seems to have different consequences in the mother, who already has a developed immune system, than in the fetus, which is vulnerable with immature defense mechanisms. Studies have shown that the presence of fetal microchimeric cells in the mother can be associated with reduced fetal growth, pre-eclampsia, miscarriage, premature birth, and the risk of autoimmune disease development in the future. However, some studies report that they may also play a positive role in the healing of maternal tissue, in cancer and cardiovascular disease. There are few studies in the literature regarding the role of maternal microchimeric cells in fetal autoimmunity. Even fewer have examined their association with the potential triggering of autoimmune diseases later in the offspring’s life. The objectives of this review were to elucidate the mechanisms underlying the potential association between maternal cells and autoimmune conditions in offspring. Based on our findings, several hypotheses have been proposed regarding possible mechanisms by which maternal cells may trigger autoimmunity. In Type 1 diabetes, maternal cells have been implicated in either attacking the offspring’s pancreatic β-cells, producing insulin, differentiating into endocrine and exocrine cells, or serving as markers of tissue damage. Additionally, several potential mechanisms have been suggested for the onset of neonatal lupus erythematosus. In this context, maternal cells may induce a graft-versus-host or host-versus-graft reaction in the offspring, function as effectors within tissues, or contribute to tissue healing. These cells have also been found to participate in inflammation and fibrosis processes, as well as differentiate into myocardial cells, potentially triggering an immune response. Moreover, the involvement of maternal microchimeric cells has been supported in conditions such as juvenile idiopathic inflammatory myopathies, Sjögren’s syndrome, systemic sclerosis, biliary atresia, and rheumatoid arthritis. Conversely, no association has been found between maternal cells and celiac disease in offspring. These findings suggest that the role of maternal cells in autoimmunity remains a controversial topic that warrants further investigation.

Fungal colonization poses a significant risk for neonates, leading to invasive infections such as fungemia. While Candida species are the most commonly identified pathogens, other rare yeasts are increasingly reported, complicating diagnosis and treatment due to limited data on antifungal pharmacokinetics. These emerging yeasts, often opportunistic, underscore the critical need for early diagnosis and targeted therapy in neonates. This systematic review aims to comprehensively analyze all published cases of neonatal fungemia caused by rare opportunistic yeasts, examining geographical distribution, species involved, risk factors, treatment approaches, and outcomes. Searching two databases (PubMed and SCOPUS), 89 relevant studies with a total of 342 cases were identified in the 42-year period; 62% of the cases occurred in Asia. Pichia anomala (31%), Kodamaea ohmeri (16%) and Malassezia furfur (15%) dominated. Low birth weight, the use of central catheters, prematurity, and the use of antibiotics were the main risk factors (98%, 76%, 66%, and 65%, respectively). 22% of the cases had a fatal outcome (80% in Asia). The highest mortality rates were reported in Trichosporon beigelii and Trichosporon asahii cases, followed by Dirkmeia churashimamensis cases (80%, 71%, and 42% respectively). Low birth weight, the use of central catheters, the use of antibiotics, and prematurity were the main risk factors in fatal cases (84%, 74%, 70%, and 67%, respectively). 38% of the neonates received fluconazole for treatment but 46% of them, died. Moreover, the rare yeasts of this review showed high MICs to fluconazole and this should be taken into account when planning prophylactic or therapeutic strategies with this drug. In conclusion, neonatal fungemia by rare yeasts is a life-threatening and difficult-to-treat infection, often underestimated and misdiagnosed.

Background/Objectives: The primary purpose of this study was to correlate the factors influencing the onset and duration of exclusive breastfeeding (EBF) and breastfeeding (BF) rates at different time points in baby-friendly hospitals (BFHs) in Greece. Methods: This study was conducted from October 2020 to January 2022. The sample consisted of 1201 mothers with corresponding newborn births out of the total 7201 that took place during the same period. We used a questionnaire that the mothers answered during the first hour after birth, before being discharged from the maternity hospital, and at the 2nd, 4th, and 6th month of the infant’s life. The results were compared with the data of the national study from 2017 (concerning births from general maternity hospitals and not only from BFHs). Results: The EBF rate within 1 h after birth was 71.3%, which gradually declined to 21.2% in the 6th month. Between the two studies, differences were recorded in BF and EBF rates at the 6th and 4th month of the infants’ life, respectively, especially in mothers who are less likely to breastfeed (e.g., those without breastfeeding experience, those over 40 years old, etc.). Conclusion: This study showed that EBF and BF rates are higher in infants born in BFHs compared to non-BFHs both during their hospitalization in the first days of life and during the first 6 months of life. BFHs also play a decisive role in mothers who, due to their socio-economic profile, have lower chances of starting to breastfeed.

Gestational diabetes mellitus (GDM) is an important health issue, as it is connected with adverse effects to the mother as well as the fetus. A factor of essence for the pathology of this disorder is the gut microbiota, which seems to have an impact on the development and course of GDM. The role of the gut microbiota on maternal reproductive health and all the changes that happen during pregnancy as well as during the neonatal period is of high interest. The correct establishment and maturation of the gut microbiota is of high importance for the development of basic biological systems. The aim of this study is to provide a systematic review of the literature on the effect of GDM on the gut microbiota of neonates, as well as possible links to morbidity and mortality of neonates born to mothers with GDM. Systematic research took place in databases including PubMed and Scopus until June 2024. Data that involved demographics, methodology, and changes to the microbiota were derived and divided based on patients with exposure to or with GDM. The research conducted on online databases revealed 316 studies, of which only 16 met all the criteria and were included in this review. Research from the studies showed great heterogeneity and varying findings at the level of changes in α and β diversity and enrichment or depletion in phylum, gene, species, and operational taxonomic units in the neonatal gut microbiota of infants born to mothers with GDM. The ways in which the microbiota of neonates and infants are altered due to GDM remain largely unclear and require further investigation. Future studies are needed to explore and clarify these mechanisms.

The human gastrointestinal ecosystem, or microbiome (comprising the total bacterial genome in an environment), plays a crucial role in influencing host physiology, immune function, metabolism, and the gut–brain axis. While bacteria, fungi, viruses, and archaea are all present in the gastrointestinal ecosystem, research on the human microbiome has predominantly focused on the bacterial component. The colonization of the human intestine by microbes during the first two years of life significantly impacts subsequent composition and diversity, influencing immune system development and long-term health. Early-life exposure to pathogens is crucial for establishing immunological memory and acquired immunity. Factors such as maternal health habits, delivery mode, and breastfeeding duration contribute to gut dysbiosis. Despite fungi’s critical role in health, particularly for vulnerable newborns, research on the gut mycobiome in infants and children remains limited. Understanding early-life factors shaping the gut mycobiome and its interactions with other microbial communities is a significant research challenge. This review explores potential factors influencing the gut mycobiome, microbial kingdom interactions, and their connections to health outcomes from childhood to adulthood. We identify gaps in current knowledge and propose future research directions in this complex field.

Background: Perinatal hypoxia may result in coagulation dysfunction. Diminished blood flow or oxygen to the fetus/neonate during the perinatal period can cause bone marrow and liver function impairment, leading to thrombocytopenia, impaired synthesis of clotting and fibrinolytic factors, and increased destruction of platelets in the small blood vessels. The goal of the present study was to evaluate the hemostatic status of newborns with perinatal hypoxia via the non-activated thromboelastometry (NATEM) assay in cord blood samples. Methods: 134 hypoxic neonates born in our maternity unit over a 1.5-year period were enrolled in this observational cohort study, and 189 healthy neonates served as the control group. Participation in the study was voluntary and parents signed informed consent prior to recruitment. Demographic and clinical data were recorded on admission, and the NATEM method was performed on cord blood samples. The following NATEM values were evaluated: clotting time (CT), alpha angle (α-angle), clot formation time (CFT), clot amplitude at 5 and 10 min. (A5, A10), maximum clot firmness (MCF), clot lysis index at 60 min. after CT (LI60), and maximum clot elasticity (MCE). Statistical analysis was conducted utilizing the SAS for Windows 9.4 software platform. Results: Neonates with perinatal hypoxia exhibited decreased fibrinolytic potential in comparison to healthy neonates, as indicated by increased LI60, and this difference was statistically significant (LΙ60: 94 (92–96) Vs 93 (91–95), p value = 0.0001). There were no statistically significant differences noted among the remaining NATEM variables. Conclusion: Our findings indicate decreased fibrinolytic potential in hypoxic neonates in comparison to healthy neonates, suggesting that NATEM could serve as an effective tool for promptly identifying hemostasis dysfunction in this group of neonates.

Background: The term congenital diaphragmatic eventration (CDE) refers to an anatomical abnormality of the diaphragm. It is a very rare condition; however, early and prompt diagnosis is of very great importance due to possible life-threatening complications. Most severely affected patients are neonates, usually presented with respiratory distress symptoms. The aim of this study was to systematically review the existing literature and to consolidate data on CDE in neonates as well as to report a case of a neonate with congenital diaphragmatic eventration of the left hemidiaphragm and clinical signs and symptoms of the gastrointestinal tract. Methods: An electronic search of the PubMed and Scopus databases was performed regarding studies evaluating the clinical presentation, diagnosis methods, treatments, and outcomes of CDE in the neonatal population. Results: Data from 93 studies were integrated into our review, reporting 204 CDE cases, and according to them, the male/female ratio was 1/1 with a predominance of right-sided eventration. The diagnosis was primarily established by chest X-ray; surgical intervention was the most frequent treatment. The recurrence rate was 8.3% (9/109 cases). Conclusions: Early and accurate diagnosis of CDE and repair of the diaphragm can prevent complications, reduce morbidity, and improve the quality of patient’s life.

Background and Objectives: congenital heart disease (CHD), cyanotic and, to a lesser degree, acyanotic, often are accompanied by coagulation abnormalities, impacting substantially morbidity and mortality. Until now, no consistent hemostatic patterns have been demonstrated in neonates and children with CHD because they represent a variable and heterogenous population. The aim of the present study is to investigate the hemostatic profile, as well as the role of ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type-1 motives), the cleaving protein of von Willebrand factor (VWF) in neonates with CHD and compare them to healthy age-matched controls. Materials and Methods: twenty neonates with a mean gestational age of 37.1 ± 2.5 weeks were included in the CHD group, and 18 healthy neonates with a mean gestational age of 38.2 ± 1.5 weeks were in the control group. Results: prothrombin time was significantly prolonged, and accordingly, factor VII (FVII) levels were significantly decreased in the CHD group in comparison to controls. Factor VIII (FVIII), VWF, and ristocetin cofactor activity (Rcof) levels were significantly higher in the study vs. control group. Concentrations of ADAMTS-13 were decreased in the CHD vs. control group, but the difference was not statistically significant. Our results, in combination, indicate a balanced hemostatic mechanism, although with greater variability in neonates with CHD, while developmental aspects of coagulation are evident in the specific patient population. Conclusions: the coagulation profile is moderately impaired early in the course of CHD, though increased thrombogenicity is already present and should not be ignored.

(1) Background: Iron is an essential metal for the proper growth and neurodevelopment of infants. To prevent and treat iron deficiency, iron supplementation or fortification is often required. It has been shown, though, that it affects the synthesis of gut microbiota. (2) Methods: This paper is a systematic review and meta-analysis of the effect of oral iron supplementation/fortification on the gut microbiota in infancy. Studies in healthy neonates and infants who received per os iron with existing data on gut microbiota were included. Three databases were searched: PUBMED, Scopus, and Google Scholar. Randomized controlled trials (RCTs) were included. Quality appraisal was assessed using the ROB2Tool. (3) Results: A total of six RCTs met inclusion criteria for a systematic review, and four of them were included in the meta-analysis using both the fixed and random effects methods. Our results showed that there is very good heterogeneity in the iron group (I2 = 62%), and excellent heterogeneity in the non-iron group (I2 = 98%). According to the meta-analysis outcomes, there is a 10.3% (95% CI: −15.0–−5.55%) reduction in the bifidobacteria population in the iron group and a −2.96% reduction for the non-iron group. There is a confirmed difference (p = 0.02) in the aggregated outcomes between iron and non-iron supplement, indicative that the bifidobacteria population is reduced when iron supplementation is given (total reduction 6.37%, 95%CI: 10.16–25.8%). (4) Conclusions: The abundance of bifidobacteria decreases when iron supplementation or fortification is given to infants.

The Special Issue has been completed with the publication of 13 review and research articles [...]

Background: Intrauterine growth restriction (IUGR) is associated with hemorrhagic and thrombotic complications during the perinatal period. Thrombocytopenia, platelet dysfunction, and prolonged standard coagulation tests are observed in this population. The aim of this study is to examine the hemostatic profile of IUGR neonates with the use of a non-activated assay (NATEM) in cord blood samples. Methods: During an 18 month period, a NATEM ROTEM assay was performed on cord blood samples of 101 IUGR neonates. A total of 189 appropriate for gestational age (AGA) neonates were used as a control group. The NATEM variables recorded include the following: clotting time (CT); clot formation time (CFT); clot amplitude at 5, 10, and 20 min (A5, A10, A20); α-angle (a°); maximum clot firmness (MCF); lysis index at 30 and 60 min (LI30, LI60); and maximum clot elasticity (MCE). Results: IUGR neonates demonstrate a hypocoagulable state, with lower A5, A10, A2, MCF, and MCE values when compared to AGA. Using multiple linear regression, we determined IUGR as an independent factor influencing all NATEM parameters (except CT and LI30) exhibiting a hypocoagulable and hypofibrinolytic profile. Platelet count was positively correlated with A5, A10, A20, MCF, alpha angle, and MCE, and negatively correlated with CFT. Conclusion: IUGR neonates appear with lower clot strength and elasticity and prolonged clot kinetics, as illustrated by ROTEM variables.

Introduction: Acrylamide, an organic compound, is, chemically speaking, a vinyl-substituted primary amide. It is produced industrially, principally as a precursor to polyacrylamides, for use in such products as plastics and cosmetics. This same compound, however, forms naturally in certain foods, both home-cooked and packaged, especially when prepared at high temperatures. We developed and validated a novel reliable technique for the determination of acrylamide in amniotic fluid. Multiple reaction monitoring (MRM) is a targeted mass spectrometry (MS) technique which enables the detection and quantification of particular molecules in a complex mixture. Thanks to its throughput, selectivity, and sensitivity, MRM-MS has been identified as offering an alternative to antibody-based studies for the purpose of biomarker verification. Our aim was to investigate the presence of acrylamide in amniotic fluid and, via the MRM-MS technique, to determine whether there is any correlation between maternal exposure to acrylamide, through a woman’s diet, and fetal growth. Methods: Our amniotic fluid bank included 40 samples from various fetal growth rates, as objectively denoted by the neonatal weight centile at delivery, while our analytical detection method was based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Acrylamide was determined with reversed phase chromatography and monitoring of two multiple reaction monitoring (MRM) transitions. Quantification was performed using the matrix-matched calibration curve. Results: Acrylamide was detected at concentrations between 7.1 and 1468 ng/mL in six out of the total of 40 amniotic fluid samples that were used. Our method limit of detection and quantification was 1.4 ng/mL and 4.6 ng/mL, respectively. The repeatability of our method ranged between 11 and 14%, expressed as relative standard deviation levels between 5 and 100 ng/mL. Conclusions: Detection of acrylamide in early second trimester amniotic fluid, for the first time in the literature to our knowledge, raises concerns about fetal health, given that published data on animal studies have attributed a number of birth defects to acrylamide. Our novel LC-MS/MS method for the determination of acrylamide in amniotic fluid proved to be effective and its performance in practice was very accurate, simple, and fast. Validation of the method revealed that the use of a matrix-matched curve is necessary for the quantification.

Neonatal sepsis is a life-threatening condition associated with significant morbidity and mortality. Sepsis-induced coagulopathy is a well-recognized entity, signifying the strong cross-talk between inflammation and coagulation. The aim of the present study was to compare the coagulation profile between the acute phase of sepsis and recovery in term and preterm neonates. Additional comparisons to healthy neonates were undertaken. Levels of clotting, anti-clotting factors and ADAMTS-13 (A disintegrin and metalloprotease with thrombospondin type-1 motives), the cleaving protein of von Willebrand factor (VWF), were measured in 16 term and preterm neonates in the acute phase of infection and following recovery, as well as in 18 healthy neonates. Clotting times were prolonged, while levels of particular clotting factors were lower in the acute phase of infection compared to controls and recovery. On the other hand, levels of fibrinogen, factor VIII (FVIII) and VWF were significantly higher in the acute phase in comparison to controls and recovery, while they remained persistently higher in the infection group compared to controls. In regard to the anticlotting mechanism, a clear suppression was observed in septic neonates. ADAMTS-13 levels were significantly lower in the acute phase of infection in comparison to controls and recovery (p = 0.015 and 0.004, respectively), while a trend toward superimposed normalization was demonstrated post infection, as higher ADAMTS-13 levels were measured in recovered neonates compared to controls (p = 0.002). The coagulation profile is considerably deranged in neonatal sepsis. ADAMTS-13 deficiency in septic neonates is a novel finding with promising future implications, as ADAMTS-13 substitution may serve as a useful therapeutic option in neonatal sepsis, prompting further investigation in future studies.

A large number of prediction models are published with the objective of allowing personalized decision making for diagnostic or prognostic purposes. Conventional statistical measures of discrimination, calibration, or other measures of model performance are not well-suited for directly and clearly assessing the clinical value of scores or biomarkers. Decision curve analysis is an increasingly popular technique used to assess the clinical utility of a prognostic or diagnostic score/rule, or even of a biomarker. Clinical utility is expressed as the net benefit, which represents the net balance of patients’ benefits and harms and considers, implicitly, the consequences of clinical actions taken in response to a certain prediction score, rule, or biomarker. The net benefit is plotted against a range of possible exchange rates, representing the spectrum of possible patients’ and clinicians’ preferences. Decision curve analysis is a powerful tool for judging whether newly published or existing scores may truly benefit patients, and represents a significant advancement in improving transparent clinical decision making. This paper is meant to be an introduction to decision curve analysis and its interpretation for clinical investigators. Given the extensive advantages, we advocate applying decision curve analysis to all models intended for use in clinical practice.

BackgroundWe aimed to develop and validate a diagnostic model for sepsis among neonates evaluated for suspected sepsis, by incorporating thromboelastometry parameters, maternal/neonatal risk factors, clinical signs/symptoms and laboratory results.MethodsThis retrospective cohort study included 291 neonates with presumed sepsis, hospitalized in a NICU, from 07/2014 to 07/2021. Laboratory tests were obtained on disease onset and prior to initiating antibiotic therapy. Τhromboelastometry extrinsically activated (EXTEM) assay was performed simultaneously and Tοllner and nSOFA scores were calculated. Sepsis diagnosis was the outcome variable. A 10-fold cross-validation least absolute shrinkage and selection operator logit regression procedure was applied to derive the final multivariable score. Clinical utility was evaluated by decision curve analysis.ResultsGestational age, CRP, considerable skin discoloration, liver enlargement, neutrophil left shift, and EXTEM A10, were identified as the strongest predictors and included in the Neonatal Sepsis Diagnostic (NeoSeD) model. NeoSeD score demonstrated excellent discrimination capacity for sepsis and septic shock with an AUC: 0.918 (95% CI, 0.884–0.952) and 0.974 (95% CI, 0.958–0.989) respectively, which was significantly higher compared to Töllner and nSOFA scores.ConclusionsThe NeoSeD score is simple, accurate, practical, and may contribute to a timely diagnosis of sepsis in neonates with suspected sepsis. External validation in multinational cohorts is necessary before clinical application.

BackgroundPlatelet function of fetal growth restricted (FGR) neonates remains a field of debate. Platelet function analyzer (PFA-100) offers a quantitative in vitro assessment of primary, platelet-related hemostasis. Our aim was to examine platelet function using PFA-100 in FGR neonates and associate our results with perinatal parameters.MethodsPFA-100 was applied on 74 FGR neonates, 48 full-term (>37 weeks' gestation) and 26 preterm neonates (

Over the last few decades, there has been an ongoing debate over both the optimal feeding mode for very premature neonates (VPN) as well as what their optimal growth should be. Despite the American Academy of Pediatric declaring since 1997 that the growth of VPN should follow the trajectory of intrauterine fetal growth, differences of opinion persist, feeding policies keep changing, and the growth and development of VPN remains extremely variable not only between countries, but even between neighboring neonatal units. Even the appropriate terminology to express poor postnatal growth (extrauterine growth restriction (EGR) and postnatal growth failure (PGF)) remains a subject of ongoing discussion. A number of recent publications have shown that by implementing breast milk fortification and closely following growth and adjusting nutrition accordingly, as per the consensus guidelines of the major Neonatal Societies, we could achieve growth that closely follows birth centiles. A recent position paper from EPSGAN recommending targeted nutritional support to cover the energy and protein deficits sustained by VPN during periods of critical illness further strengthens the above findings. Conclusion: We can promote better growth of VPN by ensuring a stable administration of sufficient calories and protein, especially in the first 2 weeks of life, implementing breast milk fortification, covering energy and protein deficits due to critical illness, and increasing feeding volumes as per the latest guidelines. The adoption of universal protocol for nutrition and growth of VPN is essential and will enable better monitoring of long-term outcomes for this population.

The prevalence of chronic maternal disease is rising in the last decades in the developed world. Recent evidence indicated that the incidence of chronic maternal disease ranges from 10 to 30% of pregnancies worldwide. Several epidemiological studies in mothers with chronic diseases have mainly focused on the risk for adverse obstetric outcomes. Evidence from these studies supports a correlation between maternal chronic conditions and adverse perinatal outcomes, including increased risk for preeclampsia, cesarean section, preterm birth, and admission in the Neonatal Intensive Care Unit (NICU). However, there is a knowledge gap pertaining to the management of these women during lactation. This review aimed at summarizing the available research literature regarding breastfeeding in mothers with chronic diseases. Adjusted and evidence-based support may be required to promote breastfeeding in women with chronic diseases; however, our comprehension of breastfeeding in this subpopulation is still unclear. The literature related to breastfeeding extends in various scientific areas and multidisciplinary effort is necessary to compile an overview of current evidence and knowledge regarding breastfeeding issues in mothers with chronic diseases.

Abstract Intrauterine growth restriction (IUGR) is a fetal adverse condition, ascribed by limited oxygen and nutrient supply from the mother to the fetus. Management of IUGR is an ongoing challenge because of its connection with increased fetal mortality, preterm delivery and postnatal pathologies. Untargeted nuclear magnetic resonance (1H NMR) metabolomics was applied in 84 umbilical cord blood and maternal blood samples obtained from 48 IUGR and 36 appropriate for gestational age (AGA) deliveries. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) followed by pathway and enrichment analysis generated classification models and revealed significant metabolites that were associated with altered pathways. A clear association between maternal and cord blood altered metabolomic profile was evidenced in IUGR pregnancies. Increased levels of the amino acids alanine, leucine, valine, isoleucine and phenylalanine were prominent in IUGR pregnancies indicating a connection with impaired amino acid metabolism and transplacental flux. Tryptophan was individually connected with cord blood discrimination while 3-hydroxybutyrate assisted only maternal blood discrimination. Lower glycerol levels in IUGR samples ascribed to imbalance between gluconeogenesis and glycolysis pathways, suggesting poor glycolysis. The elevated levels of branched chain amino acids (leucine, isoleucine and valine) in intrauterine growth restricted pregnancies were linked with increased insulin resistance.

Human milk (HM) of mothers infected with or vaccinated against SARS-CoV-2 contains specific immunoglobulins, which may protect their offspring against infection or severe disease. The time frame and duration after infection or vaccination, during which these immunoglobulins are detected in HM, as well as the major factors that influence their levels, have not been fully elucidated. This systematic review aimed to collect the existing literature and describe the immune response, specifically regarding the immunoglobulins in HM after COVID-19 disease or vaccination in non-immune women. We conducted a systematic search of PubMed and Scopus databases to identify studies published up until 19 March 2023. In total, 975 articles were screened, and out of which 75 were identified as being relevant and were finally included in this review. Infection by SARS-CoV-2 virus primarily induces an IgA immune response in HM, while vaccination predominantly elevates IgG levels. These immunoglobulins give HM a neutralizing capacity against SARS-CoV-2, highlighting the importance of breastfeeding during the pandemic. The mode of immune acquisition (infection or vaccination) and immunoglobulin levels in maternal serum are factors that seem to influence immunoglobulin levels in HM. Further studies are required to determine the impact of other factors, such as infection severity, lactation period, parity, maternal age and BMI on immunoglobulin level in HM.

Τhe importance of the gut microbiome and its functions has only recently been recognized and researched in greater depth. The establishment of the human gut microbiome begins in utero, forming its adult-like phenotype in the first 2–3 years of life. Several factors affect and alter the gut microbiome composition and its metabolic functions, such as early onset of breastfeeding, mode of delivery, antibiotic administration, or exposure to chemical substances, among others. Existing data support the important connection between health status and gut microbiome homeostasis. In cases when this balance is disturbed, several disorders may arise, such as inflammatory reactions that lead to atopy, eczema, or allergic asthma. The so-called gut-brain axis refers to the complex biochemical pathways between the central nervous system and the gastrointestinal system. One of the most fascinating areas of ongoing research is the broad spectrum of neurodevelopmental disorders (NDDs) and how gut health may be associated with such disorders. The prevalence of NDDs, such as autism spectrum disorder or attention deficit hyperactivity disorder, has increased over recent years. Whether gut microbiota homeostasis plays a role in these disorders is not yet fully understood. The aim of this narrative review is to provide an account of current knowledge on how gut health is linked with these disorders. We performed a literature review in order to identify and synthesize available data that highlights the potential association between NDDs and a balanced gut microbiome in terms of composition and proper function. The connection between the gut microbiome and NDDs offers promising new opportunities for future research.

Significant cross talk occurs between inflammation and coagulation. Thus, coagulopathy is common in sepsis, potentially aggravating the prognosis. Initially, septic patients tend to exhibit a prothrombotic state through extrinsic pathway activation, cytokine-induced coagulation amplification, anticoagulant pathways suppression, and fibrinolysis impairment. In late sepsis stages, with the establishment of disseminated intravascular coagulation (DIC), hypocoagulability ensues. Traditional laboratory findings of sepsis, including thrombocytopenia, increased prothrombin time (PT) and fibrin degradation products (FDPs), and decreased fibrinogen, only present late in the course of sepsis. A recently introduced definition of sepsis-induced coagulopathy (SIC) aims to identify patients at an earlier stage when changes to coagulation status are still reversible. Nonconventional assays, such as the measurement of anticoagulant proteins and nuclear material levels, and viscoelastic studies, have shown promising sensitivity and specificity in detecting patients at risk for DIC, allowing for timely therapeutic interventions. This review outlines current insights into the pathophysiological mechanisms and diagnostic options of SIC.

(1) Background: Although invasive fungal infections are a major cause of neonatal morbidity and mortality, data on the incidence and outcomes of localized abscesses in solid organs due to fungal infections are scarce. The aim of this study was to consolidate evidence and enhance our understanding on neonatal liver abscesses due to invasive fungal infections. (2) Methods: An electronic search of the PubMed and Scopus databases was conducted, considering studies that evaluated fungal liver abscesses in the neonatal population. Data on the epidemiology, clinical course, treatment, and outcome of these infections were integrated in our study. (3) Results: Overall, 10 studies were included presenting data on 19 cases of neonatal fungal liver abscesses. Candida spp. were the most common causative pathogens (94.7%). Premature neonates constituted the majority of cases (93%), while umbilical venous catheter placement, broad spectrum antibiotics, and prolonged parenteral nutrition administration were identified as other common predisposing factors. Diagnosis was established primarily by abdominal ultrasonography. Medical therapy with antifungal agents was the mainstay of treatment, with Amphotericin B being the most common agent (47%). Abscess drainage was required in four cases (21%). Eradication of the infection was achieved in the majority of cases (80%). (4) Conclusions: Even though fungal liver abscess is a rare entity in the neonatal population, clinicians should keep it in mind in small, premature infants who fail to respond to conventional treatment for sepsis, particularly if an indwelling catheter is in situ. A high index of suspicion is necessary in order to achieve a timely diagnosis and the initiation of the appropriate treatment.

Background: The term “bacterial translocation” (BT) refers to the migration of bacteria or their products from the gastrointestinal tract to tissues located outside it, and may occur after intestinal ischemia-reperfusion injury. The term “endotoxin” is synonymous, and is used interchangeably with the term lipopolysaccharide (LPS). LPS, a component of Gram-negative gut bacteria, is a potent microbial virulence factor, that can trigger production of pro-inflammatory mediators, causing localized and systemic inflammation. The aim of this study is to investigate if neonatal asphyxia provokes BT and an increased concentration of LPS in an animal model of asphyxia in piglets. Methods: Twenty-one (21) newborn male Landrace/Large White piglets, 1–4 days old, were randomly allocated into three groups, Control (A), Asphyxia (B) and Asphyxia-Cardiopulmonary Resuscitation (CPR) (C). All animals were instrumented, anesthetized and underwent hemodynamic monitoring. In Group A, the animals were euthanized. In Group B, the endotracheal tube was occluded to cause asphyxia leading to cardiopulmonary arrest. In Group C, the animals were resuscitated after asphyxia and further monitored for 30′. Bacterial translocation was assessed by the measurement of endotoxin in blood from the portal vein and the aorta, and also by the measurement of endotoxin in mesenteric lymph nodes (MLNs) at euthanasia. The results are given as median (IQR) with LPS concentration in EU/mL. Results: BT was observed in all groups with minimum LPS concentration in the MLN and maximum concentration in the portal vein. LPS levels in the MLNs were higher in the Group B: 6.38 EU/mL (2.69–9.34) compared to the other groups (Group A: 2.1 EU/mL (1.08–2.52), Group C: 1.66 EU/mL (1.51–2.48), p = 0.012). The aorta to MLNs LPS difference (%) was lower in Group B: 0.13% (0.04–1.17), compared to Group A: 5.08% (2.2–10.7), and Group C: 3.42% (1.5–5.1)) (p = 0.042). The same was detected for portal to MLNs LPS difference (%) which was lower in Group B: 0.94% (0.5–3) compared to Group A: 4.9% (4–15), and Group C: 3.85% (1.5–5.1)) (p = 0.044). Conclusions: Neonatal asphyxia can provoke ΒΤ and increased LPS concentration in blood and tissue located outside the gastrointestinal system.

Streptococcus gallolyticus (S. gallolyticus) has been linked to the development of infections in adults; however, in neonates S. gallolyticus sepsis is very rare and resembles Group B Streptococcal infections. In this case report, we present the case of a full-term neonate who developed early-onset sepsis due to S. gallolyticus. A systematic review of the literature was also conducted. The neonate had good APGAR scores at 1′ and 5′. At 5 h postnatally, the neonate developed poor feeding and respiratory distress. She received oxygen in a head box, and a complete blood count and biochemistry, blood, CSF and body surface cultures were obtained. Empiric intravenous antibiotics (ampicillin and tobramycin) were initiated, and she was transferred to a tertiary NICU for further treatment. The neonate was mechanically ventilated and received dopamine and colloid fluids for circulatory support. A cardiology consultation revealed pulmonary hypertension on day one. S. gallolyticus was isolated in the blood culture. Central nervous system ultrasonography, brainstem auditory evoked potentials, and a second cardiology evaluation were normal on day three. Clinical and laboratory improvement was noted on day three, and the baby was discharged after a 12-day hospitalization. Follow-up visits were scheduled for reevaluation.

Background: Exclusive breastfeeding (EBF) remains the cornerstone of infant nutrition for the first six months of life, presenting multiple short and long term benefits. The purpose of this study is the demonstration of EBF rates of infants born in baby-friendly hospitals (BFH) and the factors that positively influence EBF. Methods: The study was conducted in all four of the BFH that exist in Greece, between 2020 and 2022. The study sample consisted of 1200 mothers, taken from the 7101 that delivered at those hospitals during the time of the study. A questionnaire was used that included questions to evaluate the infant’s nutrition after birth, after exiting the maternity hospital and during the 2nd, 4th and 6th month of age. The WHO guidelines on EBF and breastfeeding (BF), as well as the “Infant and Young Child Feeding” indicators, were used. Results: The EBF rate within 1 h after birth was 71.3%, which gradually declined to 21.2% in the 6th month. The respective rate of BF was 94.5% and declined to 66.1%. The logistic regression revealed that attending antenatal breastfeeding courses, vaginal delivery, full-term pregnancies and the mothers’ advanced education level constitute independent positive prognostic factors for increased EBF rates. Conclusion: The results of the first national study on BFH are presented. Despite the improvement of EBF rates in Greece, compared to the latest available data from 2018, reinforcement of EBF promotion measures is required in order to approach the WHO’s targets by 2025.

Premature birth is a major cause of mortality and morbidity in the pediatric population. Because their immune, gastrointestinal and nervous systems are not fully developed, preterm infants (

Introduction: The admission of neonates to Neonatal Intensive Care Units (NICUs) has been identified as a primary inhibiting factor in the establishment of breastfeeding. The aims of this study were to (1) estimate the prevalence and duration of breastfeeding in infants/toddlers who had been admitted to an NICU in Greece and (2) to investigate factors, associated with the NICU stay, which affected the establishment and maintenance of breastfeeding in infants/toddlers previously admitted to the NICU. Materials and methods: Data for this cohort study were retrieved from interviews with mothers of infants/toddlers who had been admitted to our NICU as neonates during the period of 2017–2019. Interviews were conducted based on a questionnaire regarding the child’s nutrition from birth to the day of the interview, including previous maternal experience with breastfeeding. Information related to the prenatal period, gestation age, delivery mode, duration of NICU stay, and neonatal feeding strategies during their hospital stay were recorded. Results: The response rate to the telephone interviews was 57%, resulting in 279 mother–infant pairs being included in this study. The results showed that 78.1% of children received maternal milk during their first days of life. Of all infants, 58.1% were exclusively breastfed during their first month, with a gradual decrease to 36.9% and 19.4% by the end of the third and sixth months of life, respectively. The prevalence of breastfed children reached 14.7% and 7.5% at the ages of twelve and eighteen months, respectively. In the multivariate analysis, prematurity emerged as an independent prognostic factor for the duration of exclusive and any breastfeeding (aHR 1.64, 95% CI: 1.03–2.62; and 1.69, 95% CI: 1.05–2.72, respectively; p < 0.05). Additionally, the nationality of the mother, NICU breastfeeding experience, the administration of maternal milk during neonatal hospital stay, and previous breastfeeding experience of the mother were independent prognostic factors for the duration of breastfeeding. Conclusions: Although breastfeeding is a top priority in our NICU, the exclusive-breastfeeding rates at 6 months were quite low for the hospitalized neonates, not reaching World Health Organization (WHO) recommendations. Mothers/families of hospitalized neonates should receive integrated psychological and practical breastfeeding support and guidance.

Neonatal platelet hemostasis, although it has been well described over the recent years, remains elusive in specific patient populations, including neonates from high-risk pregnancies, such as those complicated with gestational diabetes mellitus (GDM). We aimed at evaluating the platelet function of neonates born to mothers with GDM using the platelet function analyzer (PFA-100). Cord blood samples were drawn from each subject and tested with two different agonists to provide two closure time (CT) values (collagen with epinephrine (COL/EPI) and collagen with adenosine diphosphate (COL/ADP)). A total of 84 and 118 neonates formed the GDM and the control group (neonates from uncomplicated pregnancies), respectively. COL/EPI CTs were prolonged in neonates from the GDM group compared to neonates from the control group, while no statistically significant difference of COL/ADP CTs was noted between the two groups, GDM and the control. Higher COL/ADP CTs were demonstrated in neonates born via cesarean section and in neonates with blood group O. A negative correlation between COL/ADP CT and gestational age, white blood cells (WBCs) and von Willebrand factor (VWF) activity was noted in neonates from the GDM group. In conclusion, neonates from the GDM group demonstrate a more hyporesponsive phenotype of their platelets, in comparison to the control neonates.

The detection of NT-proBNP levels both in umbilical cord blood (UCB) samples and in serum samples collected from healthy term neonates during the neonatal period. A systematic review of relevant literature in accordance with PRISMA guidelines was conducted. For quality appraisal, the potential risk of bias was assessed using the BIOCROSS evaluation tool. The random-effects and fixed-effects models were used to calculate weighted mean differences with a corresponding 95% confidence interval. A total of forty (40) studies met the inclusion criteria for the systematic review. After further examination, eighteen (18) studies (1738 participants) from the UCB sample group and fourteen (14) studies (393 participants) from the serum sample group were selected to perform a meta-analysis. Using the fixed-effects model, the mean intervals of NT-proBNP in UCB and serum samples were 492 pg/mL (95% CI: 480–503 pg/mL) and 1341 pg/mL (95% CI: 1286–1397 pg/mL), respectively. A higher concentration of ΝΤ-proBNP was observed in the serum sample group compared to the UCB samples (p < 0.001). We present the intervals of NT-proBNP in UCB and in the serum of healthy term neonates. The determination of the potential effect of perinatal factors on the biomarker’s reference range was also aimed.

The aim of this systematic review and meta-analysis is the comparison of endotracheal intubation and suctioning to immediate resuscitation without intubation of non-vigorous infants > 34 weeks’ gestation delivered through meconium-stained amniotic fluid (MSAF). Randomized, non-randomized clinical trials and observational studies were included. Data sources were PubMed/Medline and Cochrane Central Registry of Controlled Trials, from 2012 to 2021. Inclusion criteria were non-vigorous infants born through MSAF with gestational age > 34 weeks and sample size ≥ 5. We calculated overall relative risks (RR) and mean differences (MD) with a 95% confidence interval (CI) to determine the impact of endotracheal suction (ETS) in non-vigorous infants born through MSAF. The outcomes presented are the incidence of neonatal mortality, meconium aspiration syndrome (MAS), transient tachypnea, need for positive pressure ventilation, respiratory support, persistent pulmonary hypertension treatment, neonatal infection, ischemic encephalopathy, admission to neonatal intensive care unit (NICU) and the duration of hospitalization between ETS and non-ETS group. Six studies with a total sample of 1026 patients fulfilled the inclusion criteria. Statistically non-significant difference was observed in RR between two groups with regards to mortality (1.22, 95% CI 0.73–2.04), occurrence of MAS (1.08, 95% CI 0.76–1.53) and other outcomes, and MD in hospitalization duration. There is no sufficient evidence to suggest initiating endotracheal suction soon after birth in non-vigorous meconium-stained infants as routine.

The non-activated thromboelastometry (NATEM) assay is a point-of-care assay that can provide a comprehensive insight into the actual hemostatic mechanism. However, there are very limited data about its use in clinical practice. The aim of this study was to systematically review the literature for any data regarding the use of NATEM in several clinical settings. A systematic review of PubMed and Scopus databases was conducted through 20 January 2022 for studies evaluating the use of the NATEM assay in different clinical settings. The literature search yielded a total of 47 publications, 30 of which met the eligibility criteria for this review. Evaluation of NATEM’s detecting ability for hemostasis disorders is limited in the literature. The results of the included studies indicate that NATEM seems to be a sensitive method for the detection of hyperfibrinolysis and may have an advantage in the diagnosis of hemostatic disorders. It could be more informative than the other ROTEM assays for detecting changes in coagulation parameters in patients who receive anticoagulants. However, the reported outcomes are highly varying among the included studies. NATEM has a high sensitivity to detect hypo- or hypercoagulability and provides a detailed insight into the whole hemostatic process from clot formation to clot breakdown. It could be a useful technique in variable fields of medicine, not only in adults, but also in pediatric and neonatal populations, to guide different hemostatic treatments and predict coagulation disorders or mortality/morbidity; this issue remains to be further investigated.

Bronchopulmonary dysplasia (BPD) is a common cause of respiratory illness in preterm newborns with high morbidity and mortality rates. At present, there are no early prognostic biomarkers that can be used in clinical practice to predict the development of BPD. In this review, we critically appraise evidence regarding the use of serum N-terminal pro-brain natriuretic peptide (NTproBNP) levels as a biomarker for BPD in neonates. Furthermore, we summarize studies assessing the feasibility of urinary NTproBNP levels as a non-invasive method to predict BPD in preterm infants. Multiple studies reported a strong association between NTproBNP serum levels and the onset of BPD. For urinary NTproBNP there is scarce evidence showing an association with BPD. Given the promising data obtained by preliminary studies, further assessment of this biomarker in both serum and urine is needed. Standardized reference values should be defined before conducting any further clinical studies.

Background: ROTEM assay has gained increasing acceptance as a method for rapid and specific coagulation pathway assessment. However, its use in the neonatal population remains limited since reference ranges have not yet been established. Aims: (1) to determine reference ranges for healthy term neonates of ROTEM parameters using non-activated assay (NATEM) in cord blood samples; (2) to assess whether delivery mode, gender, gestational age, birth weight and blood group (ABO and Rhesus) of the neonate, coagulation disorder and anticoagulant medication of the mother have an impact on NATEM parameters. Methods: NATEM assay was conducted in cord blood samples of 189 term neonates without any medical history. Results: Reference ranges (2.5th and 97.5th percentiles) are established for clotting time (CT), clot formation time (CFT), α-angle, clot amplitude at 5, 10 and 20 min (A5, A10, A20), maximum clot firmness (MCF), lysis index at 30 and 60 min (LI30, LI60, %) and maximum clot elasticity (MCE). Reference ranges for NATEM are CT 182–499 s, CFT 63–176 s, α-angle 58–78°, A5 28–52 mm, A10 37–61 mm, A20 42–66 mm, MCF 43–67 mm, LI30 97–100%, LI60 87–98% and MCE 75–203. Male neonates appear to be more hypocoagulable than females. Conclusions: We demonstrate reference ranges for healthy term neonates in NATEM assay that could be used as a reference group for future studies of neonates with an underlying pathology.

Purpose: The composition and the metabolic activity of the gut microbiota of breastfed and formula-fed infants has been the focus of several studies over the last two decades. Gene sequencing techniques and metabolomics in biological samples have led to expansion of our knowledge in this field. A more thorough comprehension of the metabolic role of the intestinal microbiota could assist and expedite the development of optimal feeding strategies. The aim of this systematic review is to present available data regarding the effect of the feed type on the infantile intestinal microbiota (microbial composition and metabolites) by DNA-sequencing and metabolome analysis of neonatal stool. Methods: A systematic search of the literature in PubMed was attempted to establish relevant studies. Randomized controlled trials studying the diversity and composition of gut microbiota and metabolites of infants that received different types of feed were included. The study subjects were infants/neonates born at term or preterm receiving either breast, donor, or formula milk. Formula could be either classic or fortified with probiotics, prebiotics, or both. The included trials compared the differences on metagenomics and metabolomics of infantile stool, aiming at investigating the beneficial effects of fortification of formula with synbiotics. Results: Out of 1452 papers identified by the initial search, seven were selected for inclusion, following screening for eligibility. Eligibility was determined by closer examination for relevance of the title, abstract, and subsequent full text. The results of these studies mostly support that the feed type modulates the microbiome composition. In terms of the alpha-diversity, no significant difference exists between the feeding groups, whereas significant differences were noted with regards to beta-diversity in breastfed and formula-fed infants. As for the microbial composition, the studies revealed different populations in the formula-fed group compared to the breastfed group at the phylum and genus level. Bifidobacteria supplementation of infant formula did not seem to change the proportions of Bifidobacterial sequences during the first year of life. Another finding according to the studies is that the pH of fecal samples in breastfed as well as prebiotic-supplemented formula-fed infants. was significantly lower than that of formula-fed infants. Infant milk formula with a mixture of prebiotics (GOS/FOS oligosaccharides) was shown to be capable of selectively stimulating the growth of Bifidobacteria with analogous changes in fecal pH and short-chain fatty acid content in fully formula-fed infants. Conclusions: Overall, there is evidence to support that feed type modulates the infants’ microbiome constitution. The impact of feeding on term and preterm microbiota could have potential benefits on intestinal functionality, immune system, and metabolism, and probably pursuing the host for life.

The microbiome is vital for the proper function of the gastrointestinal tract (GIT) and the maintenance of overall wellbeing. Gut ischemia may lead to disruption of the intestinal mucosal barrier, resulting in bacterial translocation. In this systematic review, according to PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines, we constructed a search query using the PICOT (Patient, Intervention, Comparison, Outcome, Time) framework. Eligible studies reported in PubMed, up to April 2021 were selected, from which, 57 publications’ data were included. According to these, escape of intraluminal potentially harmful factors into the systemic circulation and their transmission to distant organs and tissues, in utero, at birth, or immediately after, can be caused by reduced blood oxygenation. Various factors are involved in this situation. The GIT is a target organ, with high sensitivity to ischemia–hypoxia, and even short periods of ischemia may cause significant local tissue damage. Fetal hypoxia and perinatal asphyxia reduce bowel motility, especially in preterm neonates. Despite the fact that microbiome arouse the interest of scientists in recent decades, the pathophysiologic patterns which mediate in perinatal hypoxia/asphyxia conditions and gut function have not yet been well understood.

Background: Galactagogues are substances that promote lactation, although data on their effects on humans remain limited. We investigated the efficacy of Silitidil to increase milk supply and duration of breastfeeding of a specific subgroup of mothers in need of lactation support. Methods: 161 mothers from November 2018 until January 2021 were the study subjects in this retrospective study; during their hospitalization, due to neonatal or maternal factors that inhibited lactation, they were prescribed galactagogues. Mothers were surveyed by telephone interview via a 13-item questionnaire. Results: 73.91%, were primigravidas, 78.26% gave birth by cesarean section (CS) and 72.05% continued to take galactagogues after hospital discharge. Of the neonates, 24.22% were preterm ≤37 weeks of gestation, and 55.9% had birth weight (BW) between 2500 and 3500 g. With respect to breastfeeding rates, 100% were breastfed during their first week, 98.8% breastfed during the first month, 87% during the first 4 months, dropping to 56.5% at 6 months, 41% at 1 year and 19.3% over 1 year of age. Conclusions: This study demonstrates that administration of a galactagogue containing Silitidil (Piulatte-Humana) improves breastfeeding rates at from 1 until 12 months of life in mothers with low milk supply during their hospital stay. Further studies are needed to generate evidence-based strategies to improve breastfeeding outcomes.

Background: Although respiratory distress syndrome (RDS) constitutes a postnatal risk factor for bleeding and thromboembolic events in neonates, few studies have addressed this issue. We aimed to evaluate the hemostatic profile of neonates with RDS using rotational thromboelastometry (ROTEM). Methods: An observational study was conducted from November 2018 to November 2020 in the NICU of General Hospital of Nikaia “Aghios Panteleimon”. Preterm and term neonates with RDS hospitalized in the NICU were included and EXTEM (tissue factor-triggered extrinsic pathway), INTEM (ellagic acid activated intrinsic pathway), and FIBTEM (with platelet inhibitor cytochalasin D) assays were performed at the onset of the disease. Results: A hypocoagulable profile was noted in neonates with RDS compared to controls, expressed as significant prolongation of EXTEM CT (clotting time) and CFT (clot formation time), lower EXTEM A10 (amplitude at 10 min), MCF (maximum clot firmness), and LI60 (lysis index). Furthermore, prolongation of INTEM CFT and FIBTEM CT, and decreased INTEM and FIBTEM A10 and MCF were found in neonates with RDS. Multivariable logistic regression analysis showed that RDS is an independent factor for the recorded alterations in ROTEM variables. Conclusions: RDS is associated with a hypocoagulable profile and greater hyperfibrinolytic potential compared to healthy neonates.

Background: To compare the prognostic accuracy of the most commonly used indexes of mortality over time and evaluate the potential of adding thromboelastometry (ROTEM) results to these well-established clinical scores. Methods: The study population consisted of 473 consecutive term and preterm critically-ill neonates. On the first day of critical illness, modified Neonatal Multiple Organ Dysfunction (NEOMOD) scoring system, Score for Neonatal Acute Physiology (SNAP II), Perinatal extension of SNAP (SNAPPE), and SNAPPE II, were calculated and ROTEM standard extrinsically activated (EXTEM) assay was performed simultaneously. Time-to-event methodology for competing-risks was used to assess the performance of the aforementioned indexes in predicting in-hospital mortality over time. Time-dependent receiver operator characteristics curves for censored observation were compared across indexes. The addition of EXTEM parameters to each index was tested in terms of discrimination capacity. Results: The modified NEOMOD score performed similarly to SNAPPE. Both scores performed significantly better than SNAP II and SNAPPE II. Amplitude recorded at 10 min (A10) was the EXTEM parameter most strongly associated with mortality (A10 < 37 mm vs. ≥37 mm; sHR = 5.52; p < 0.001). Adding A10 to each index apparently increased the prognostic accuracy in the case of SNAP II and SNAPPE II. However, these increases did not reach statistical significance. Conclusion: Although the four existing indexes considered showed good to excellent prognostic capacity, modified NEOMOD and SNAPPE scores performed significantly better. Though larger studies are needed, adding A10 to well-established neonatal severity scores not including biomarkers of coagulopathy might improve their prediction of in-hospital mortality.

Introduction: The effects of “aggressive” neonatal feeding policies of very preterm neonates (VPN) and the risk of metabolic syndrome later in life remain questionable. We aimed to evaluate the effect of our “aggressive” nutrition policies of VPN during hospitalisation on body mass index (BMI) at ages 2 and 8 years. Materials and Methods: Eighty four VPN, who received “aggressive” nutrition during hospitalisation in an effort to minimise postnatal growth restriction (PGR) (group A), and 62 term neonates, as controls (group B), were enrolled in the study. Group A was further divided in four subgroups depending on the type (A1: fortified expressed breast milk and preterm formula; A2: exclusively preterm formula) and quantity of milk received (A3: maximum feeds 180–210 mL/kg/day; A4: maximum feeds 210 and up to 260 mL/kg/day). BMI was calculated at ages 2 and 8 years and plotted on the centile charts. Results: There was no significant difference in BMI between groups A and B at 2 and 8 years, respectively, in both absolute BMI values and their centile chart distribution. There was no significant difference in BMI at 2 and 8 years either between subgroups A1 and A2 or between subgroups A3 and A4. Conclusions: “Aggressive” and individualised feeding policy for VPN did not affect the BMI and obesity rates at ages of 2 and 8 years in our study population. The type and quantity of milk feeds had no impact on their BMI at school age. Further larger studies are needed to confirm our results.

Background: We aimed to evaluate gastric volume changes during intermittent milk feeds (IMF) and continuous milk feeds (CMF) in very premature neonates (VPN), with gastric residual volume (GRV) based on antral cross-sectional area (ACSA) measurements and to examine if there were differences in GRV between the two feeding methods. Methods: A randomized prospective clinical trial with crossover design was conducted in 31 preterm neonates (gestational age < 30 weeks). Gastric volume was assessed twice in each neonate (during IMF and CMF feeding), at 7 specific time points during a 2-h observation period by measuring ACSA changes via the ultrasound (U/S) method. Results: There was a significantly different pattern of gastric volume changes between the two feeding methods. GRV, expressed as the median percentage of ACSA measurement at 120 min relative to the higher ACSA measurement during IMF, was found to be 3% (range 0–25%) for IMF and 50% (range 15–80%) for CMF. Neonates fed with IMF had a shorter mean gastric emptying time compared to those fed with CMF (p = 0.0032). No signs of feeding intolerance were recorded in either group during the period of observation. Conclusions: Our results showed that gastric volume changes and gastric emptying time in VPN, based on ACSA measurement changes, depend on the milk feeding method. No gastrointestinal complications/adverse events were noted with GRV up to 80% with CMF.

Background: Thromboelastometry (ROTEM), as a point of care test, is an attractive tool for rapid evaluation of hemostasis. Currently, no reference ranges exist for all ROTEM assays in neonates, limiting its use in this vulnerable population. The aim of the present study was: (1) to establish reference ranges for standard extrinsically activated (EXTEM), intrinsically activated (INTEM), and fibrinogen polymerization (FIBTEM) ROTEM assays in whole blood samples of healthy term neonates; (2) to determine the impact of gender, delivery mode, and hematocrit on ROTEM parameters. Methods: EXTEM, INTEM, and FIBTEM ROTEM assays were performed simultaneously with complete blood count in 215 healthy term neonates. Results: Reference ranges (2.5th and 97.5th percentiles) were obtained for clotting time (CT), clot formation time (CFT), α-angle, clot firmness at 10 min (A10), maximum clot firmness (MCF), and lysis index at 60 min (LI60, %). Reference ranges for EXTEM were CT 38–78 s, CFT 49–148 s, A10 40–65 mm, and MCF 47–69 mm, LI60 83–98%. For INTEM, CT 134–270 s, CFT 50–142 s, A10 41–63 mm, and MCF 48–67 mm, LI60 85–97%, and finally, for FIBTEM: CT 36–85 s, A10 9–25 mm and MCF 10–26 mm, LI60 92–100%. Hematocrit values were positively correlated with CT, CFT and negatively with A10, MCF values. Conclusion: This study provides, for the first time, reference ranges for ROTEM EXTEM/INTEM/FIBTEM values simultaneously in healthy term neonates. The combined evaluation of ROTEM tests increases its diagnostic accuracy, contributing to the expansion of ROTEM use in the neonatal population.

Background: We aimed to assess whether nucleated red blood cells (NRBCs) count could serve as a diagnostic and prognostic biomarker for morbidity and mortality in critically ill neonates. Methods: The association between NRBCs count and neonatal morbidity and mortality was evaluated in an observational cohort of critically ill neonates hospitalized in our neonatal intensive care unit over a period of 69 months. The discriminative ability of NRBCs count as diagnostic and prognostic biomarkers was evaluated by performing the Receiver Operating Characteristics (ROC) curve analysis. Results: Among 467 critically ill neonates included in the study, 45 (9.6%) of them experienced in-hospital mortality. No statistically significant difference was found with regards to NRBCs count between survivors and non-survivors, although the median value for NRBCs was sometimes higher for non-survivors. ROC curve analysis showed that NRBCs is a good discriminator marker for the diagnosis of perinatal hypoxia in neonates with area under the curve (AUC) [AUC 0.710; 95% confidence interval (CI), 0.660–0.759] and predominantly in preterm neonates (AUC 0.921 (95% CI, 0.0849–0.0993)) by using a cut-off value of ≥11.2%, with 80% sensitivity and 88.7% specificity. NRBCs also revealed significant prognostic power for mortality in septic neonates (AUC 0.760 (95% CI, 0.631–0.888)) and especially in preterms with sepsis (AUC 0.816 (95% CI, 0.681–0.951)), with cut-off value ≥ 1%, resulting in 81.6% sensitivity and 78.1% specificity. Conclusion: NRBCs count may be included among the early diagnostic and prognostic markers for sick neonates.

We have read the article entitled “Applying Methods for Postnatal Growth Assessment in the Clinical Setting: Evaluation in a Longitudinal Cohort of Very Preterm infants” by Montserrat Izquierdo Renau et al [...]

Perineal groove is a well-defined clinical entity that belongs to a broader group of anorectal malformations. It is characterized by a non-epithelialized mucous membrane that appears as an erythematous sulcus in the perineal midline, extending from the posterior vaginal fourchette to the anterior anal orifice. The defect is gradually cicatrized, unless there are complications like infection, defecation disorders, trauma, and bleeding. The differential diagnosis includes several other conditions like trauma, infection, irritant dermatitis, lichen sclerosis, and ulcerated hemangioma. Since it is a rare malformation, it is often misdiagnosed and its presence often elicits unnecessary diagnostic workup and intervention. In this respect, neonatologists, dermatologists, or pediatric surgeons may under- or overestimate it. We report four cases of perineal groove out of 2250 live births at a Greek Maternity Hospital between September 2016 and April 2019. The “high” incidence of perineal groove cases in our Department allowed us to familiarize with this rare defect and minimize our clinical interventions.

Background and Objective: Peripherally inserted central catheters (PICC) and umbilical venous catheters (UVC) are frequently used for vascular access in neonatal intensive care units (NICUs). While there is a significant need for these devices for critically ill neonates, there are many complications associated with their use. We aimed at investigating the incidence of UVC and PICC complications in very low birth weight (VLBW) infants. Materials and Methods: This is an observational study performed with neonates of the tertiary General Hospital of Piraeus, Greece, during an 18 month-period. Seventy-one neonates were recruited and divided into two groups: 34 neonates with PICC and 37 neonates with UVC. We recorded: Catheter dwell time, the causes of catheter removal, other complications, infections, and catheter tip colonization rates. Results: No significant statistical differences were noticed between the 2 study groups with regards to demographic characteristics, causes for catheter removal, catheter indwelling time or the incidence of nosocomial infection. Eleven UVC tips and no PICC tips were proved colonized (p = 0.001) following catheter removal. Conclusions: The incidence of complications associated with the use of UVCs and PICCs in VLBW infants did not significantly differ in our study. Their use seems to be equally safe. Further studies, with larger samples, are necessary to confirm our results.