Late Sepsis Research Articles

Retinopathy of Prematurity in Eight Portuguese Neonatal Intensive Care Units: Incidence, Risk Factors, and Progression-A Prospective Multicenter Study.

Retinopathy of prematurity (ROP) is a retinal neovascular disease affecting preterm infants. Identifying risk factors for its development and progression is critical for effective screening and prevention. This study aimed to analyze the incidence of ROP and identify key risk factors for its development and progression. We conducted a prospective, observational cohort study on 455 neonates (gestational age [GA] < 32 weeks or birth weight < 1500 g) across eight Portuguese NICUs. ROP incidence was 37.8%, with 4.6% requiring treatment. Multivariate analysis identified low GA and the number of red blood cell (RBC) transfusions as significant factors for ROP development and progression. After adjusting for these variables, platelet transfusions, high maximum fraction of inspired oxygen (FiO2) in the second week, and surfactant use remained significantly associated with ROP development, while early and late sepsis, maternal chronic hypertension, and delayed enteral nutrition were associated with progression to ROP requiring treatment. These findings underscore the importance of addressing low GAs and adult RBC transfusions in ROP risk management and suggest that maximum FiO2, platelet transfusions, and sepsis also play crucial roles. Larger studies are needed to validate these results and explore preventive interventions, particularly regarding the impact of multiple adult RBC transfusions on fetal hemoglobin percentages.

RecAP administration ameliorates sepsis outcomes through modulation of gut and liver inflammation

Sepsis, broadly described as a systemic infection, is one of the leading causes of death and long-term disability worldwide. There are limited therapeutic options available that either improve survival and/or improve the quality of life in survivors. Ilofotase alfa, also known as recombinant alkaline phosphatase (recAP), has been associated with reduced mortality in a subset of patients with sepsis-associated acute kidney injury. However, whether recAP exhibits any therapeutic benefits in other organ systems beyond the kidney is less clear. The objective of this study was to evaluate the effects of recAP on survival, behavior, and intestinal inflammation in a mouse model of sepsis, cecal ligation and puncture (CLP). Following CLP, either recAP or saline vehicle was administered via daily intraperitoneal injections to determine its treatment efficacy from early through late sepsis. We found that administration of recAP suppressed indices of inflammation in the gut and liver but did not improve survival or behavioral outcomes. These results demonstrate that recAP's therapeutic efficacy in the gut and liver may provide a valuable treatment to improve long-term outcomes in sepsis survivors.

Bacterial profile of Early versus Late onset neonatal sepsis and its antimicrobial susceptibility: A 1-year retrospective study in a tertiary level teaching hospital of Nepal

Bacterial profile of Early versus Late onset neonatal sepsis and its antimicrobial susceptibility: A 1-year retrospective study in a tertiary level teaching hospital of Nepal

Cluster of Differentiation 163 Level in the Blood as a Predictor of Early and Late Onset Neonatal Sepsis

Cluster of Differentiation 163 Level in the Blood as a Predictor of Early and Late Onset Neonatal Sepsis

Newer Insights in Etiology and Pathogenesis of Neonatal Sepsis

Neonatal sepsis is a pathophysiological response to the presence of microorganisms or their toxins in the blood during the first 28 days of life. Despite advances in neonatal intensive therapy and care, sepsis is still an important cause of morbidity and mortality in neonates, especially preterm and low birth weight neonates. Early neonatal sepsis manifests itself in the first 72 hours of life. The main risk factor for early neonatal sepsis is chorioamnionitis, and the most important causative are Streptococcus group B and Escherichia coli. Late neonatal sepsis manifests itself after 72 hours of life, and most often occurs in preterm neonates. Among the causative agents of late neonatal sepsis, coagulase-negative Staphylococcus dominates. The neonates are highly dependent of the innate immune system to defend against infection. In the pathophysiological response of the organism to infection, microcirculation, neutrophils and monocytes are first activated, and then the complement and the coagulation system. Also, mitochondrial dysfunction contributes to tissue damage in neonatal sepsis. The delayed response of adaptive immunity in the neonatal period is compensated by transplacental transfer of IgG antibodies originated from the mother, but also the IgA antibodies that the neonates receive from mother's milk. Compared to adults, the immune response have quantitative and qualitative differences, which contributes to their increased susceptibility to infection.

Community-acquired neonatal SARS-CoV-2 infection: case report

Background and Objectives: Data collection on the incidence of COVID-19 is conducted less frequently in newborns (NB) than in adults. In view of the small number of described neonatal SARS-CoV-2 infections, in this study, we report a clinical case of community-acquired COVID-19 infection in a newborn. Methods: Clinical characteristics were collected from the medical records from April 2021 until the final outcome of the newborn in May 2021. Results: This article discusses the case of a full-term male newborn aged 38 weeks. On the 17th day of life, this newborn was admitted to the pediatric unit with fever and zone 4 jaundice, mild lower chest retraction and tachypnea. The mother was diagnosed with COVID-19. Late neonatal sepsis with pulmonary focus was detected. The newborn was hospitalized and the antigen test for COVID-19 came back positive. The condition of the neonate rapidly deteriorated and he was referred to the neonatal intensive care unit (NICU), where he was intubated and placed on pressure-controlled mechanical ventilation. During his second week in the NICU, he developed severe pulmonary hypertension with decreased peripheral oxygen saturation and tachycardia. The newborn required blood transfusion and was put into prone position during part of the treatment. Reductions in mechanical ventilation parameters were not tolerated by the NB’s organism and he developed progressive hypoxemia. The newborn died 1 month and 3 days after hospitalization. Conclusion: Our study shows a case of community-acquired COVID-19 that progressed to the severe form of the disease.

Perinatal Outcome of Previable Premature Rupture of Membranes Before 24 Weeks of Gestation: A Single-Centered Retrospective Cohort Ctudy

OBJECTIVE: Preterm premature rupture of membranes (PPROM) has unfavorable consequences for the neonate and the mother if it occurs before 24 weeks of gestation. We aim to present our series to elucidate the course of previable PPROM and to detect maternal and neonatal outcomes. STUDY DESIGN: A single-centered retrospective cohort study that involves singleton patients diagnosed with spontaneous PPROM before 24 weeks. Data were retrieved from medical records, and maternal and neonatal outcomes were noted. RESULTS: Seventy-eight women were diagnosed with PPROM before 24 weeks, 42 patients (54%) opted for termination of pregnancy, and seven patients (9%) had spontaneous abortion. Twentynine patients (37%) gave live birth after a median latency of 47 days. Neonatal complications were respiratory distress syndrome (n=19; 65%), early sepsis (n=10; 34%), late sepsis (n=5; 17%), bronchopulmonary dysplasia (n=5;17%), retinopathy of prematurity (n=3; 10%), pneumothorax (n=5; 17%), intracranial hemorrhage (n=2; 6%), necrotizing enterocolitis (n=1; 3%) and meningitis (n=1; 3%). In the liveborn group, the neonatal survival rate was 62%. Of the survivors, twelve babies (66%) were discharged without composite neonatal morbidity. Maternal complications in the expectant management group included clinical chorioamnionitis (n=12, 33%) and placental abruption (n=2, 5%). CONCLUSION: In previable PPROM, overall half of the babies survive after expectant management. While a prolonged latency period and subsequent delivery at advanced gestational ages improve neonatal outcomes, such a conservative approach poses a substantial risk for chorioamnionitis.

Role of Serum Pancreatic Stone Protein as a New Biomarker for Diagnosis of Late Onset Neonatal Sepsis

Role of Serum Pancreatic Stone Protein as a New Biomarker for Diagnosis of Late Onset Neonatal Sepsis

Late Neonatal Sepsis in Very-low-birth-weight Premature Newborns Is Associated With Alterations in Neurodevelopment at Twenty-five Months of Age.

To evaluate the impact of late-onset sepsis (LOS) on the neurodevelopment of very-low-birth-weight (VLBW) premature infants. This is a retrospective cohort study of VLBW premature infants. The Mental Development Index (MDI) was determined for a population of 546 VLBW infants, at 14 and 25 months of age, and evaluated using the Bayley test. A history of meningitis or early neonatal sepsis was considered an exclusion criterion. The study parameters analyzed included perinatal variables, the development of neonatal comorbidities and a history of LOS. Multivariate linear regression and multinomial logistic regression analyses were performed. LOS was observed in 115 newborns, among whom microbiological testing showed that 65.0% presented Gram-positive bacteria, with Staphylococcus epidermidis being responsible for 55.4%. There was a significant association between the 25-month MDI and a history of LOS. This represents a decrease of 7.9 points in the MDI evaluation of newborns with a history of LOS. The latter history is also associated with the following neurodevelopmental alternations: mild motor disorders [odds ratio (OR): 2.75; 95% confidence intervals (CI): 1.07-7.05], moderate cognitive delay (OR: 3.07; 95% CI: 1.17-8.00) and cerebral palsy (OR: 2.41; 95% CI: 1.09-5.35). In our study cohort, LOS was associated with alterations in neurodevelopment, including reduced MDI, together with motor and cognitive disorders and cerebral palsy. To improve neurodevelopmental outcomes in this group of newborns, neonatal intensive care unit personnel should focus attention on preventing hospital-acquired infections.

Unveiling Dynamic Changes and Regulatory Mechanisms of T Cell Subsets in Sepsis Pathogenesis.

The pathogenesis of T cell subsets in sepsis during the body's resistance to infection is currently unknown. We aimed to investigate the dynamics and molecular mechanisms of T cells during the development of sepsis. Perform single-cell data analysis on peripheral blood mononuclear cells (PBMCs) specimen samples from seven healthy controls, five early-stage sepsis patients, and four late sepsis patients, and the atlas were mapped and analyzed using reference mapping to identify the T cell subpopulations specific to early sepsis. Expression network upstream to investigate the changes of regulatory transcription factors and pathways by pySCENIC. Twenty-two CD4+ T-cell subpopulations and 10 CD8+ T-cell subpopulations were identified by mapping analysis. At the early stage of sepsis, we observed altered ratios of multiple immune cells in PBMCs. Three cell types CD4 Tn cells, CD8 (GZMK+ early Tem), and CD8 (ZNF683+CXCR6- Tm) showed an upward trend (p < 0.05) in the early stages of sepsis compared to normal and returned to normal levels after two weeks. In addition, we found the presence of four sepsis-specific transcription factors (MXI1, CHD1, ARID5A, KLF9) in these three types of cells, which were validated in two external datasets. The differentially expressed genes in CD4 Tn cells, CD8 (GZMK+ early Tem), and CD8 (ZNF683+CXCR6- Tm) cells between the healthy group and the early-stage sepsis group are commonly enriched in the allograft rejection pathway. In addition, it was found that CD8 cells exhibit a trend towards differentiation into CD8 Temra cells in sepsis. We successfully depicted the dynamic changes of T cell subsets during sepsis onset and progression, which provides important clues for an in-depth understanding of T cells' function and regulatory mechanisms during sepsis pathogenesis.

Assessment of the prevalence of meningitis in clinically suspected cases of early and late onset neonatal sepsis

Background: Meningitis is more common in the neonatal period than any other time in life and is an important cause of morbidity and mortality globally. In India, rate of neonatal sepsis is reported 0.5 per 1000 live births. The major burden of neonatal sepsis and meningitis occurs in the developing world. According to WHO estimates there are approximately 5 million neonatal deaths in a year. The objective of the study is to assess the prevalence of meningitis in neonates with clinical suspicion of sepsis. Methods: The study was conducted among suspected cases of neonatal septicemia in neonatal intensive care unit (NICU), department of pediatrics, VPIMS, Lucknow. It is a prospective observational study. A total of 180 neonates were included in the study. Results: Out of 180 neonates, CSF examination of 131 (72.78%) neonates was normal, of 37 (20.56%) was suggestive of meningitis. Prevalence of meningitis in neonatal sepsis was 20.0%. It was 18.0% in early neonatal sepsis and 32.6% in late neonatal sepsis cases. Conclusions: The findings of present study suggested that there is a high risk of meningitis among neonatal sepsis cases. Cases with risk factors like twin birth, anemia, low TLC, low platelet count, acid-base imbalance and X-ray findings suggestive of pneumonitis should be kept in a high-risk category.

Malat1 regulates PMN-MDSC expansion and immunosuppression through p-STAT3 ubiquitination in sepsis.

Myeloid-derived suppressor cells (MDSCs) expand during sepsis and contribute to the development of persistent inflammation-immunosuppression-catabolism syndrome. However, the underlying mechanism remains unclear. Exploring the mechanisms of MDSCs generation may provide therapeutic targets for improving immune status in sepsis. Here, a sepsis mouse model is established by cecal ligation and perforation. Bone marrow cells at different sepsis time points are harvested to detect the proportion of MDSCs and search for differentially expressed genes by RNA-sequence. In lethal models of sepsis, polymorphonuclear-MDSCs (PMN-MDSCs) decrease in early but increase and become activated in late sepsis, which is contrary to the expression of metastasis-associated lung adenocarcinoma transcript 1 (Malat1). In vivo, Malat1 inhibitor significantly increases the mortality in mice with late sepsis. And in vitro, Malat1 down-regulation increases the proportion of PMN-MDSCs and enhanced its immunosuppressive ability. Mechanistically, Malat1 limits the differentiation of PMN-MDSCs by accelerating the degradation of phosphorylated STAT3. Furthermore, Stattic, an inhibitor of STAT3 phosphorylation, improves the survival of septic mice by inhibiting PMN-MDSCs. Overall, the study identifies a novel insight into the mechanism of sepsis-induced MDSCs and provides more evidence for targeting MDSCs in the treatment of sepsis.

Evidence on the benefits of probiotics for preterm infants.

This article reviews the evidence for the use of different strains of probiotics in the prevention of prevalent pathologies in premature neonates. A systematic review was conducted of the use of probiotics in neonates with less than 37 weeks of gestational age, based on a search for systematic reviews and observational and experimental studies performed during the period from January 2014 to February 2021. For this purpose, the PubMed, MEDLINE and Cochrane Library databases were consulted. The aim of this article was to review the existing data on the relationship between the administration of probiotics (with different strains and doses) and the risk of necrotising enterocolitis, mortality, late sepsis and other disease parameters in premature infants. The literature search obtained 240 articles, of which we selected 16, representing a total sample of over 200,000 premature infants. Analysis of the data obtained reveals statistical evidence that the combined administration of probiotics (especially of Lactobacillus and Bifidobacterium strains) reduces the incidence of grade II or higher necrotising enterocolitis, all-cause mortality, late sepsis, length of hospital stay and time until complete enteral nutrition is achieved. However, no benefits were apparent with respect to alleviating bronchopulmonary dysplasia, retinopathy of prematurity or intraventricular haemorrhage. Further research is needed to determine the most appropriate strains, doses and treatment duration for preterm infants to achieve the health benefits identified.

Matrix metalloproteinase-8 regulates dendritic cell tolerance in late polymicrobial sepsis via the nuclear factor kappa-B p65/β-catenin pathway.

Tolerogenic dendritic cells (DCs) are associated with poor prognosis of sepsis. Matrix metalloproteinases (MMPs) have been shown to have immunomodulatory effects. However, whether MMPs are involved in the functional reprogramming of DCs is unknown. The study aims to investigate the role of MMPs in sepsis-induced DCs tolerance and the potential mechanisms. A murine model of late sepsis was induced by cecal ligation and puncture (CLP). The expression levels of members of the MMP family were detected in sepsis-induced tolerogenic DCs by using microarray assessment. The potential roles and mechanisms underlying MMP8 in the differentiation, maturation and functional reprogramming of DCs during late sepsis were assessed both in vitro and in vivo. DCs from late septic mice expressed higher levels of MMP8, MMP9, MMP14, MMP19, MMP25 and MMP27, and MMP8 levels were the highest. MMP8 deficiency significantly alleviated sepsis-induced immune tolerance of DCs both in vivo and in vitro. Adoptive transfer of MMP8 knockdown post-septic bone marrow-derived DCs protected mice against sepsis-associated lethality and organ dysfunction, inhibited regulatory T-cell expansion and enhanced Th1 response. Furthermore, the effect of MMP8 on DC tolerance was found to be associated with the nuclear factor kappa-B p65/β-catenin pathway. Increased MMP8 levels in septic DCs might serve as a negative feedback loop, thereby suppressing the proinflammatory response and inducing DC tolerance.

Clinical value of prognostic nutritional index in predicting the presence and severity of neonatal sepsis

Aim: The Prognostic Nutritional Index (PNI) is a novel inflammation biomarker that reflects the nutritional and inflammatory status of patients. While there are studies on its use in cancer, cardiovascular, and renal diseases, there are no studies on preterm neonatal late sepsis. This study aims to emphasize the value of PNI in neonatal sepsis. Materials and Methods: Newborns with a birth weight of less than 1500 grams and a gestational age of less than 32 weeks, along with healthy controls, were included in the study. The ability of PNI to predict sepsis, septic shock, and mortality was evaluated. Results: PNI was an independent and inversely related parameter to the presence and severity of neonatal sepsis. The cut-off value of PNI to predict the presence of sepsis was ≤49.5, with a sensitivity of 98.3% (95% CI: 91.1-100.0) and a specificity of 96% (95% CI: 86.3-99.5). The area under the curve (AUC) was 0.995 (95% CI: 0.957-1.000) (p&lt;0.001). The optimum cut-off value of PNI to predict the presence of septic shock was ≤37.1, with a sensitivity of 92.3% (95% CI: 64.0-99.8) and a specificity of 77.3% (95% CI: 67.7-85.2). The AUC was 0.894 (95% CI: 0.821-0.945) (p&lt;0.001). The optimum cut-off value of PNI to predict mortality was ≤37, with a sensitivity of 92.3% (95% CI: 64.0-99.8) and a specificity of 78.4% (95% CI: 68.8-86.1). The AUC was 0.899 (95% CI: 0.827-0.948) (p&lt;0.001). Conclusion: PNI can be used as an independent dynamic biomarker to predict the presence and prognosis of neonatal sepsis.

Contato pele a pele e sepse tardia em recém-nascidos com peso até 1.800g: estudo de coorte

Abstract Objectives: to evaluate the association between the time to initiate the first skin-to-skin contact (SSC) and the daily practice time with the rates of late-onset sepsis in newborns ≤1,800g. Methods: a multicentric cohort study was carried out at the neonatal units located in three Brazilian geographic regions. The SSC time was recorded in individual files by the hospital staff and the newborn’s parents. Maternal and neonatal data were obtained from medical records and through questionnaires applied to the mothers. Data analysis was carried out using a tree algorithm classification, which divided the data set into mutually exclusive subsets that best described the variable response. Results: 405 newborns participated in the study, with an average of 31.3 ± 2.7 weeks and 1,412g (QR=1,164-1,605g) as a median birth weight. The first SSC was carried out within 137 hours of life (≤5.7 days) was associated with a lower rate of late sepsis (p=0.02) for newborns who underwent daily SSC of 112.5 to 174.7 min/day (1.9 to 2.9h/day), with a reduction in the sepsis rate from 39.3% to 27.5%. Furthermore, the duration of SSC &gt;174.7min/day (&gt;2.9h/day) was relevant (p&lt;0.001) for newborns who weighed &gt;1,344g, with a reduction in this rate from 24.1% to 6%. Conclusions: SSP has been proven to be significant in reducing late-onset sepsis rates in preterm newborns, especially when carried out in a timely manner (≤5.7 days) and prolonged (&gt;2.9h/day).

PENGEMBANGAN INSTRUMEN PENGETAHUAN DAN SIKAP IBU DALAM MELAKUKAN PERAWATAN NEONATUS BERBASIS PEMODELAN RASCH

Late sepsis in babies aged 7 days or more is caused by a lack of cleanliness in newborn care by the mother. Maternal knowledge regarding neonatal care skills still needs to be considered. This research uses an instrument that must be tested for validity and reliability based on Rasch modeling so that it can be seen which question numbers are too difficult and too easy to answer so that the instrument can be accepted in research. Validity and reliability tests can use the Rasch modeling application formula (Rasch model). The aim of this research is to validate and reliability research instruments regarding mothers' knowledge and attitudes in carrying out neonatal care. The design in this research uses quantitative analysis by adopting 3 research journals. This questionnaire was tested on 30 pregnant women at the Independent Practice of Midwife Ana Mariana. The research results showed that the questionnaire was valid and reliable, meaning it was said to be suitable for use by the general public. The results of the validity test value for row variance explained by size and raw unexplained variance (total) for knowledge and attitudes are between 40-60% with Good criteria. Meanwhile, the reliability test uses item reliability and Cronbach alpha in the good category. The results found that the questionnaire was valid and reliable, meaning it could be used as a research instrument in subsequent research.

Twinning as a risk factor for neonatal acute intestinal diseases: a case-control study.

Acute intestinal diseases (AID), including necrotizing enterocolitis and spontaneous intestinal perforation, are a group of conditions that typically present in preterm infants, and are associated with an elevated mortality and morbidity rate. The risk factors for these diseases remain largely unknown. The aim of the study is to identify the correlation between twinning and the development of AID. A single-center retrospective case-control study was conducted. We recruited all infants with a diagnosis of AID, confirmed by anatomopathology, recovered in NICU between 2010 and 2020. Considering the rarity of the outcome, 4 matched controls for each subject were randomly chosen from the overall population of newborns. Odds Ratio (OR) and 95% Confidence Interval (CI) were calculated using a conditional logistic regression model and a multivariate model by the creation of a Directed Acyclic Graph (www.dagitty.net). The study population resulted in 65 cases and 260 controls. The two groups present similar median gestational age and mean birthweight in grams. The cases have a higher frequency of neonatal pathology (defined as at least one of patent ductus arteriosus, early or late sepsis, severe respiratory distress) (84.6% vs. 51.9%), medically assisted procreation (33.8% vs. 18.8%) and periventricular leukomalacia (10.8% vs. 2.7%), and a lower frequency of steroids prophylaxis (67.7% vs. 86.9%). About 50% of cases needed surgery. The OR for the direct effect were difference from one using logistic regression booth without and with repeated measures statements: from 1.14 to 4.21 (p = .019) and from 1.16 to 4.29 (p = .016), respectively. Our study suggests that twinning may be a risk factor for the development of AID. Due to the small number of cases observed, further studies on larger populations are needed.

Effect of ethanol exposure on innate immune response in sepsis.

Alcohol use disorder, reported by 1 in 8 critically ill patients, is a risk factor for death in sepsis patients. Sepsis, the leading cause of death, kills over 270,000 patients in the United States alone and remains without targeted therapy. Immune response in sepsis transitions from an early hyperinflammation to persistent inflammation and immunosuppression and multiple organ dysfunction during late sepsis. Innate immunity is the first line of defense against pathogen invasion. Ethanol exposure is known to impair innate and adaptive immune response and bacterial clearance in sepsis patients. Specifically, ethanol exposure is known to modulate every aspect of innate immune response with and without sepsis. Multiple molecular mechanisms are implicated in causing dysregulated immune response in ethanol exposure with sepsis, but targeted treatments have remained elusive. In this article, we outline the effects of ethanol exposure on various innate immune cell types in general and during sepsis.

Comparison of Derangement of Cerebrospinal Fluid Markers in Neonates with Early and Late-Onset Sepsis

Objective: To compare derangement of cerebrospinal fluid markers in neonates with early and late-onset sepsis managed at the Neonatal Intensive Care Unit. Study Design: Comparative cross-sectional study. Setting and Duration of Study: Neonatology Department, Pak Emirates Military Hospital, Rawalpindi Pakistan, from Jul 2021 to Jun 2022. Methodology: This study was conducted on neonates managed at our Neonatal Intensive Care Unit for late or early-onset sepsis. A consultant neonatologist diagnosed neonatal sepsis based on clinical and laboratory findings. The cerebrospinal fluid routine examination was performed on all the study participants, and the derangement of various markers was compared in neonates with early and late-onset sepsis. Results: A total of 348 neonates admitted to the neonatal intensive care unit with sepsis were included in the final analysis. The mean age of the newborns included in the study was 5.38±4.53 days. Out of all the neonates in the study, 194(55.7%) had early-onset sepsis, while 154(44.3%) neonates had late-onset sepsis. All the cerebrospinal fluid markers were statistically significantly deranged in patients with late-onset sepsis (p-value&lt;0.005). Conclusion: Derangement of cerebrospinal fluid markers was seen more in patients with late-onset neonatal sepsis admitted to the neonatal intensive care unit. Emphasis should be laid on performing this necessary investigation timely in neonates with late-onset sepsis as chances of meningeal involvement are higher in this group.