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Neonatal sepsis remains a major health issue worldwide, especially for low-birth weight and premature infants, with a high risk of death and devastating sequelae. Apart from antibiotics and supportive care, there is an unmet need for adjunctive treatments to improve the outcomes of neonatal sepsis. Strong and long-standing research on adult patients has shown that vascular endothelium is a key player in the pathophysiology of sepsis and sepsis-associated organ failure, through a direct interaction with pathogens, leukocytes, platelets, and the effect of soluble circulating mediators, in part produced by endothelial cells themselves. Despite abundant evidence that the neonatal immune response to sepsis is distinct from that of adults, comparable knowledge on neonatal vascular endothelium is much more limited. Neonatal endothelial cells express lower amounts of adhesion molecules compared to adult ones, and present a reduced capacity to neutralize reactive oxygen species. Conversely, available evidence on biomarkers of endothelial damage in neonates is not as robust as in adult patients, and endothelium-targeted therapeutic opportunities for neonatal sepsis are almost unexplored. Here, we summarize current knowledge on the structure of neonatal vascular endothelium, its interactions with neonatal immune system and possible endothelium-targeted diagnostic and therapeutic tools for neonatal sepsis. Furthermore, we outline areas of basic and translational research worthy of further study, to shed light on the role of vascular endothelium in the context of neonatal sepsis.

OBJECTIVE:To investigate the impact of different stages of intrauterine inflammation (IUI) on neonatal outcomes, before and after adjusting for gestational age (GA) and other perinatal confounders. METHODS:This was an observational, prospective, single-center cohort study including all eligible neonates with GA < 35 weeks and/or birth weight ≤ 1500 g born at a 3rd level Neonatal Intensive Care Unit between 2011 and 2014. Pathological patterns of placenta, membranes and cord were classified according to Redline's criteria. Multivariable linear and logistic regression models were applied, either including or not GA among the covariates. RESULTS:Of the 807 enrolled neonates, 134 (16.6%) had signs of IUI: among these, 54.5% showed just histological chorioamnionitis (HCA), 25.4% had HCA + funisitis (FUN) stage 1, and 20.1% had HCA + FUN stage 2-3. At univariate analysis, HCA increased the risk for retinopathy of prematurity (ROP) and bronchopulmonary dysplasia, while FUN (any stage) had a deleterious impact on all outcomes investigated. After adjustment for covariates not including GA, HCA was a risk factor only for ROP (OR = 2.8, CI: 1-7.8), while FUN (any stage) was still associated with increased ORs for all outcomes (p

Extremely preterm babies are at major risk for adverse neurodevelopmental outcome, being the gestational age (GA) the main determinant for a good-quality survival. Aim of this retrospective study was to investigate the neurodevelopmental outcome in a population of extremely preterm babies admitted to a single neonatal tertiary care unit over an 8-year period. All babies born between 23+0 and 25+6 weeks of GA from January 2003 until December 2010 were retrospectively enrolled. Perinatal and neonatal variables were recorded. Motor and cognitive development was assessed using the neurofunctional scale (NFS) and the Griffith’s scales at 2 years. Fifty-five out of 122 infants survived to discharge. Survival rates doubled for each additional gestational week from 23 to 25: 16%, 38% and 74% at 23, 24 and 25 weeks GA respectively. Forty-six infants were evaluated at 2 years. A poor cognitive and motor outcome was observed in all babies born at 23 weeks. Griffith’s general quotient (GQ) was ≥76 in 62% and ≥88 in 33% of babies born between 24 and 25 weeks. No severe motor disabilities were found in 81% of babies born between 24 and 25 weeks. Preterm premature rupture of membranes, absence of prenatal steroids, intrauterine growth restriction, male, lower GA and major brain abnormalities at magnetic resonance imaging (MRI) were significantly associated with worse NFS and lower mean GQ at 2 years of age. GA, gender and abnormal MRI findings remained significantly associated with impaired NFS at the multivariate analysis. Survival rates and neurodevelopmental outcome improved with each week of GA. These results are relevant for clinicians counselling families facing an unavoidable extremely preterm birth.

Background. Serratia marcescens, a Gram-negative organism, is a well-recognized nosocomial pathogen, especially in Neonatal Intensive Care Units (NICUs). Even if multiple point sources have been identified, the source of an outbreak often remains unknown. Because an outbreak of S. marcescens can spread rapidly, closing the Unit sometimes is necessary. Here, we report on an outbreak of S. marcescens occurred in our NICU and describe the control measures taken to stop the epidemic without closing the Unit. Material and Methods. Our Unit is a 56-bed Unit composed of two areas: a 23-bed (4 rooms) intensive-care and a 33-bed (6 rooms) intermediate-care area. After some cases of S. marcescens infection were identified during a 3-month period, a prospective epidemiological study was performed in both areas during a period of 8 months. Surveillance cultures were obtained from all neonates (pharynx, rectum, eyes, ears) at admission, at room-changing and twice weekly, from medical and nursing staff (pharynx, rectum) and from the environment (sinks, ventilators, incubators, soap dispensers, disinfectants, breast pumps, work surfaces). The following control measures were also taken: universal precautions were intensified (handwashing, gloves, masks), education of the staff was stressed, a survey was instituted to check the observance of the control measures, admissions to the NICU were limited and infected/colonized babies were strictly cohorted. Because the outbreak continued despite these control measures, we separated new admissions from hospitalized babies by using two ways in the Unit: a clean way (green) and a dirty way (red) with nurses, rooms and everything different between the green and the red babies. Results. During the study period, 589 neonates underwent surveillance cultures (14.156 samples); 32/589 (5%) infants had positive swabs. Four (12.5%) of the 32 colonized infants had clinical signs of infection: sepsis-like symptoms (2 cases) and conjunctivitis (2 cases). Twenty-two (68.8%) of the 32 colonized infants became positive in the intensive-care area; the median time from admission to the first positive culture was 13 days (range 6-83). Risk factors for infection/colonization were low birthweight (green way and the red way.Conclusions. In this outbreak, no evidence of environmental or staff reservoirs was shown. Transmission was likely horizontal, from newborn to newborn, through the hands of medical and nursing staff and the infected/colonized infants were themselves the reservoir of the pathogen. Probably, the organism was introduced into our NICU from an ex-preterm patient from another hospital (index case). The use of a clean way and a dirty way, in addition to the other control measures, appeared the most effective practice to stop the epidemic without closing the Unit.

Identifying single nucleotide polymorphisms (SNPs) in the genes involved in sepsis may help to clarify the pathophysiology of neonatal sepsis. The aim of this study was to evaluate the relationships between sepsis in pre-term neonates and genes potentially involved in the response to invasion by infectious agents. The study involved 101 pre-term neonates born between June 2008 and May 2012 with a diagnosis of microbiologically confirmed sepsis, 98 pre-term neonates with clinical sepsis and 100 randomly selected, otherwise healthy pre-term neonates born during the study period. During the study, 47 SNPs in 18 candidate genes were genotyped on Guthrie cards using an ABI PRISM 7900 HT Fast real-time and MAssARRAY for nucleic acids instruments. Genotypes CT and TT of rs1143643 (the IL1β gene) and genotype GG of rs2664349GG (the MMP-16 gene) were associated with a significantly increased overall risk of developing sepsis (p = 0.03, p = 0.05 and p = 0.03), whereas genotypes AG of rs4358188 (the BPI gene) and CT of rs1799946 (the DEFβ1 gene) were associated with a significantly reduced risk of developing sepsis (p = 0.05 for both). Among the patients with bacteriologically confirmed sepsis, only genotype GG of rs2664349 (the MMP-16 gene) showed a significant association with an increased risk (p = 0.02). Genotypes GG of rs2569190 (the CD14 gene) and AT of rs4073 (the IL8 gene) were associated with a significantly increased risk of developing severe sepsis (p = 0.05 and p = 0.01). Genotype AG of rs1800629 (the LTA gene) and genotypes CC and CT of rs1341023 (the BPI gene) were associated with a significantly increased risk of developing Gram-negative sepsis (p = 0.04, p = 0.04 and p = 0.03). These results show that genetic variability seems to play a role in sepsis in pre-term neonates by influencing susceptibility to and the severity of the disease, as well as the risk of having disease due to specific pathogens.