Antibiotics and beyond: Unraveling the dynamics of bronchopulmonary dysplasia in very preterm infants.

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains a significant challenge in neonatal care. Prenatal inflammation and neonatal sepsis contribute to the multifactorial nature of BPD. A potential association between empirical antibiotic therapy and BPD risk has been proposed due to microbiota dysbiosis in very low birth weight premature infants. METHODS: A single centered retrospective cohort study of preterm infants (24-32 weeks gestation) from 2014 to 2021. The study compared groups that received empirical antibiotics in the first days of life and those that did not receive any antibiotic in the first days of life. The primary outcomes studied were BPD, death, and the combined outcome of BPD/death. Statistical analysis employed t-tests, Mann-Whitney U, Chi-square, and logistic regression. RESULTS: Of 454 preterm infants, 61.5% received antibiotics. This group had lower gestational age, birth weight, and Apgar scores. Antibiotic use was associated with higher incidence of BPD (35.5% vs. 10.3%), death (21.5% vs. 8.6%), and combined outcomes (54.5% vs. 18.3%). In multivariate analysis, antibiotic use independently associated with BPD (OR 2.58, p < 0.001) and combined outcome BPD/death (OR 2.06, p < 0.02). Antenatal corticosteroids provided protection against BPD, but not mortality. CONCLUSION: This study suggests an association between early empirical antibiotic use and BPD in preterm infants, emphasizing the need for judicious antibiotic practices in neonatal care.

Herpes virus entry mediator signaling blockade produces mortality in neonatal sepsis through induced cardiac dysfunction.

Introduction: Sepsis remains a major source of morbidity and mortality in neonates, and characterization of immune regulation in the neonatal septic response remains limited. HVEM is a checkpoint regulator which can both stimulate or inhibit immune responses and demonstrates altered expression after sepsis. We hypothesized that signaling via HVEM would be essential for the neonatal response to sepsis, and that therefore blockade of this pathway would improve survival to septic challenge. Methods: To explore this, neonatal mice were treated with cecal slurry (CS), CS with Anti-HVEM antibody (CS-Ab) or CS with isotype (CS-IT) and followed for 7-day survival. Mice from all treatment groups had thymus, lung, kidney and peritoneal fluid harvested, weighed, and stained for histologic evaluation, and changes in cardiac function were assessed with echocardiography. Results: Mortality was significantly higher for CS-Ab mice (72.2%) than for CS-IT mice (22.2%). CS resulted in dysregulated alveolar remodeling, but CS-Ab lungs demonstrated significantly less dysfunctional alveolar remodeling than CS alone (MCL 121.0 CS vs. 87.6 CS-Ab), as well as increased renal tubular vacuolization. No morphologic differences in alveolar septation or thymic karyorrhexis were found between CS-Ab and CS-IT. CS-Ab pups exhibited a marked decrease in heart rate (390.3 Sh vs. 342.1 CS-Ab), stroke volume (13.08 CS-IT vs. 8.83 CS-Ab) and ultimately cardiac output (4.90 Sh vs. 3.02 CS-Ab) as well as a significant increase in ejection fraction (73.74 Sh vs. 83.75 CS-Ab) and cardiac strain (40.74 Sh vs. 51.16 CS-Ab) as compared to CS-IT or Sham animals. Discussion: While receptor ligation of aspects of HVEM signaling, via antibody blockade, appears to mitigate aspects of lung injury and thymic involution, stimulatory signaling via HVEM still seems to be necessary for vascular and hemodynamic resilience and overall neonatal mouse survival in response to this experimental polymicrobial septic insult. This dissonance in the activity of anti-HVEM neutralizing antibody in neonatal animals speaks to the differences in how septic cardiac dysfunction should be considered and approached in the neonatal population.

New and old lessons from a devastating case of neonatal E coli meningitis.

BACKGROUND: Neonatal Escherichia coli (E coli) meningitis results in significant morbidity and mortality. We present a case of a premature infant with extensive central nervous system (CNS) injury from recurrent E coli infection and the non-traditional methods necessary to identify and clear the infection. CASE PRESENTATION: The infant was transferred to our institution's pediatric intensive care unit (PICU) after recurrence of E coli CNS infection requiring neurosurgical intervention. He had been treated for early onset sepsis (EOS) with ampicillin and gentamicin for 10 days followed by rapid development of ampicillin-resistant E coli septic shock and meningitis after discontinuation of antibiotics. Sterility of the CNS was not confirmed at the end of 21 days of cefepime therapy and was subsequently followed by recurrent ampicillin-resistant E coli septic shock and CNS infection. Despite 6 weeks of appropriate therapy with sterility of CSF by traditional methods, he suffered from intractable seizures with worsening hydrocephalus. Transferred to our institution, he underwent endoscopic 3rd ventriculostomy with cyst fenestration revealing purulent fluid and significant pleocytosis. An additional 3 weeks of systemic and intraventricular antibiotics with cefepime and tobramycin were given but a significant CNS neutrophil-predominant pleocytosis persisted (average of ∼ 21,000 cells/mm3). Repeated gram stains, cultures, polymerase chain reaction (PCR) testing, and metagenomic next generation sequencing (NGS) testing of CSF were negative for pathogens but acridine orange stain (AO) revealed numerous intact rod-shaped bacteria. After the addition of ciprofloxacin, sterility and resolution of CSF pleocytosis was finally achieved. CONCLUSION: Neonatal E coli meningitis is a well-known entity but unlike other bacterial infections, it has not proven amenable to shorter, more narrow-spectrum antibiotic courses or limiting invasive procedures such as lumbar punctures. Further, microbiologic techniques to determine CSF sterility suffer from poorly understood limitations leading to premature discontinuation of antibiotics risking further neurologic damage in vulnerable hosts.

Short-term variation of the fetal heart rate as a marker of intraamniotic infection in pregnancies with preterm prelabor rupture of membranes: a historical cohort study.

INTRODUCTION: Intraamniotic infection (IAI) and subsequent early-onset neonatal sepsis (EONS) are among the main complications associated with preterm prelabor rupture of membranes (PPROM). Currently used diagnostic tools have been shown to have poor diagnostic performance for IAI. This study aimed to investigate whether the exposure to IAI before delivery is associated with short-term variation of the fetal heart rate in pregnancies with PPROM. METHODS: Observational cohort study of 678 pregnancies with PPROM, delivering between 24 + 0 and 33 + 6 gestational weeks from 2012 to 2019 in five labor units in Stockholm County, Sweden. Electronic medical records were examined to obtain background and exposure data. For the exposure IAI, we used the later diagnosis of EONS in the offspring as a proxy. EONS is strongly associated to IAI and was considered a better proxy for IAI than the histological diagnosis of acute chorioamnionitis, since acute chorioamnionitis can be observed in the absence of both positive microbiology and biochemical markers for inflammation. Cardiotocography traces were analyzed by a computerized algorithm for short-term variation of the fetal heart rate, which was the main outcome measure. RESULTS: Twenty-seven pregnancies were categorized as having an IAI, based on the proxy diagnosis of EONS after birth. Fetuses exposed to IAI had significantly lower short-term variation values in the last cardiotocography trace before birth than fetuses who were not exposed (5.25 vs 6.62 ms; unadjusted difference: -1.37, p = 0.009). After adjustment for smoking and diabetes, this difference remained significant. IAI with a later positive blood culture in the neonate (n = 12) showed an even larger absolute difference in STV (-1.65; p = 0.034), with a relative decrease of 23.5%. CONCLUSION: In pregnancies with PPROM, fetuses exposed to IAI with EONS as a proxy have lower short-term variation of the fetal heart rate than fetuses who are not exposed. Short-term variation might be useful as adjunct surveillance in pregnancies with PPROM.

Preterm infant with necrotizing enterocolitis and arteritis secondary to streptococcus gallolyticus subspecies pasteurianus.

 Streptococcus gallolyticus subspecies pasteurianus is a subtype of Streptococcus bovis (S. bovis) that has become increasingly recognized as a sepsis-causing pathogen in neonates. It is well documented that S. bovis species have a predilection to both cardiac and gastrointestinal tissue, and in adult populations, isolating these organisms in the bloodstream often triggers further evaluation for co-morbid complications such as colon cancer or endocarditis. However, no such guidance currently exists in neonatal literature. We present a case of a preterm infant with S. gallolyticus subsp. pasteurianus bacteremia presenting as necrotizing enterocolitis (NEC) not previously described in the literature. Furthermore, through a complete diagnostic evaluation, including an echocardiogram, our patient was found to have the rare complication of endocarditis.

The Novel MFG-E8-derived Oligopeptide, MOP3, Improves Outcomes in a Preclinical Murine Model of Neonatal Sepsis.

INTRODUCTION: Neonatal sepsis is a devastating inflammatory condition that remains a leading cause of morbidity and mortality. Milk fat globule-EGF-factor VIII (MFG-E8) is a glycoprotein that reduces inflammation, whereas extracellular cold-inducible RNA binding protein (eCIRP) worsens inflammation. This study aimed to determine the therapeutic potential of a novel MFG-E8-derived oligopeptide 3 (MOP3) designed to clear eCIRP and protect against inflammation, organ injury, and mortality in neonatal sepsis. METHODS: C57BL6 mouse pups were injected intraperitoneally with cecal slurry (CS) and treated with MOP3 (20 µg/g) or vehicle. 10 h after injection, blood, lungs, and intestines were collected for analyses, and in a 7-day experiment, pups were monitored for differences in mortality. RESULTS: MOP3 treatment protected septic pups from inflammation by reducing eCIRP, IL-6, TNFα, and LDH. MOP3 reduced lung and intestinal inflammation and injury as assessed by reductions in tissue mRNA levels of inflammatory markers, histopathologic injury, and apoptosis in lung and intestines. MOP3 also significantly improved 7-day overall survival for CS-septic mouse pups compared to vehicle (75% vs. 46%, respectively). CONCLUSION: Deriving from MFG-E8 and designed to clear eCIRP, MOP3 protects against sepsis-induced inflammation, organ injury, and mortality in a preclinical model of neonatal sepsis, implicating it as an exciting potential new therapeutic. LEVEL OF EVIDENCE: Level 1.

Neonatal sepsis and its predictors in Ethiopia: umbrella reviews of a systematic review and meta-analysis, 2023.

Background: Although neonatal sepsis is acknowledged as the primary cause of newborn death in Ethiopia, data on its impact at the national level are limited. Strong supporting data are required to demonstrate how this affects neonatal health. This umbrella study was conducted to determine the overall prevalence of newborn sepsis and its relationship with maternal and neonatal factors. Methods: This umbrella review included five articles from various databases. The AMSTAR-2 method was used to assess the quality of included systematic review and meta-analysis studies. STATA Version 18 software was used for statistical analysis. A random-effects model was used to estimate the overall effects. Results: In this umbrella review, 9032 neonates with an outcome of interest were included. The overall pooled prevalence of neonatal sepsis was 45% (95% CI: 39-51%; I2=99.34). The overall pooled effect size showed that prematurity was significantly associated with neonatal sepsis [odds ratio=3.11 (95% CI: 2.22-3.99)]. Furthermore, maternal factors are strongly associated with neonatal sepsis. Conclusions: Nearly half of Ethiopian neonates are affected by neonatal sepsis. It is critical to reduce premature birth, low birth weight, and preterm membrane rupture to reduce the incidence of neonatal sepsis. Furthermore, it is preferable to design and strengthen policies and programs aimed at improving maternal nutritional status and treating maternal infections, which all contribute to lowering the burden of neonatal sepsis.

Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis: A prospective study of diagnostic accuracy.

OBJECTIVES: We evaluated the diagnostic accuracy of cerebrospinal fluid (CSF) inflammatory markers for diagnosing bacterial meningitis in neonates with sepsis and/or meningitis. METHODS: Cases were identified from a prospective multicenter study including patients aged 0-3 months with Group B Streptococcal (GBS) or Escherichia coli culture positive sepsis/meningitis. CSF CXCL10, MDC, IL-6, IL-8, IL-10, TNF- α, MIF, IL-1RA, CXCL13, IL-1ß, CRP and procalcitonin concentrations were measured with Luminex technology. RESULTS: In 61/373 patients (17%) residual CSF from the lumbar puncture was available, of whom 16 (26%) had definitive meningitis, 15 (25%) probable meningitis and 30 (49%) had sepsis. All biomarkers were detectable in CSF and showed significantly higher concentrations in definitive meningitis versus sepsis patients and six biomarkers in probable meningitis versus sepsis patients. Discrimination between definitive meningitis and sepsis was excellent for IL-1RA (area under the receiver operating characteristic curve [AUC] 0.93), TNF-α (AUC 0.92), CXCL10 (AUC 0.90), IL-1ß (AUC 0.92), IL-6 (AUC 0.94), IL-10 (AUC 0.93) and a combination of IL-1RA, TNF-α, CXCL-10 and CSF leukocyte count (AUC 0.95). CSF leukocyte count remained the predictor with the highest diagnostic accuracy (AUC 0.96). CONCLUSION: CSF inflammatory markers can be used to differentiate between neonatal sepsis and meningitis.

Early-onset group B streptococcal infections in five Nordic countries with different prevention policies, 1995 to 2019.

BackgroundNeonatal early-onset disease caused by group B Streptococcus (GBS) is a leading cause of infant morbidity. Intrapartum antibiotic prophylaxis (IAP) is effective in preventing early-onset GBS disease, but there is no agreement on the optimal strategy for identifying the pregnant women requiring this treatment, and both risk-based prophylaxis (RBP) and GBS screening-based prophylaxis (SBP) are used.AimThe aim of this study was to evaluate the effect of SBP as a public health intervention on the epidemiology of early-onset GBS infections.MethodsIn 2012, Finland started the universal SBP, while Denmark, Iceland, Norway and Sweden continued with RBP. We conducted an interrupted time series analysis taking 2012 as the intervention point to evaluate the impact of this intervention. The incidences of early- and late-onset GBS infections during Period I (1995-2011) and Period II (2012-2019) were collected from each national register, covering 6,605,564 live births.ResultsIn Finland, a reduction of 58% in the incidence of early-onset GBS disease, corresponding to an incidence rate ratio (IRR) of 0.42 (95% CI: 0.34-0.52), was observed after 2012. At the same time, the pooled IRR of other Nordic countries was 0.89 (95% CI: 0.80-1.0), specifically 0.89 (95% CI: 0.70-1.5) in Denmark, 0.34 (95% CI: 0.15-0.81) in Iceland, 0.72 (95% CI: 0.59-0.88) in Norway and 0.97 (95% CI: 0.85-1.1) in Sweden.ConclusionsIn this ecological study of five Nordic countries, early-onset GBS infections were approximately halved following introduction of the SBP approach as compared with RBP.

Improved efficiency in the management of newborns with infectious risk factors by the sepsis risk calculator and clinical observation

Abstract Objective To evaluate the efficiency of the sepsis risk calculator and the serial clinical observation in the management of late preterm and term newborns with infectious risk factors. Method Single-center, observational, two-phase cohort study comparing the rates of neonates born ≥35 weeks' gestation, ≥2000 g birthweight, and without major congenital anomalies, who were screened and/or received antibiotics for early-onset neonatal sepsis risk at our center during two periods, before (January/2018-June/2019) and after (July/2019-December/2020) the implementation of the sepsis risk calculator. Results A total of 1796 (Period 1) and 1867 (Period 2) patients with infectious risk factors were included. During the second period, tests to rule out sepsis were reduced by 34.0 % (RR, 95 %CI): 0.66 (0.61, 0.71), blood cultures by 13.1 %: 0.87 (0.77, 0.98), hospital admissions by 13.5 %: 0.86 (0.76, 0.98) and antibiotic administration by 45.9 %: 0.54 (0.47, 0.63). Three cases of early-onset neonatal sepsis occurred in the first period and two in the second. Clinical serial evaluation would have detected all true cases. Conclusions The implementation of a sepsis risk calculator in the management of newborns ≥35 weeks GA, ≥2000 g birthweight, without major congenital anomalies, with infectious risk factors is safe and adequate to reduce laboratory tests, blood cultures, hospital admissions, and antibiotics administration. Serial clinical observation, in addition, could be instrumental to achieve or even improve this goal.

Prevalence of early neonatal sepsis and positive maternal culture for group B beta-hemolytic Streptococcus

SUMMARY OBJECTIVE: The aim of this study was to evaluate the prevalence of early neonatal sepsis in pregnant women with a positive culture for group B beta-hemolytic Streptococcus in a middle-income city in Southeastern Brazil. METHODS: A retrospective cohort study was conducted, involving singleton low- and high-risk pregnancies in whom group B beta-hemolytic Streptococcus cultures were evaluated between 35 and 37 weeks of gestation using vaginal and anal swabs. A specific medium (Todd-Hewitt) was used for culturing. The pregnant women were divided into two groups based on positive (n==201) and negative (n==420) cultures for group B beta-hemolytic Streptococcus. RESULTS: The maternal colonization rate by group B beta-hemolytic Streptococcus was 32.3%. The prevalence of early neonatal sepsis was 1.0% (2/201) among patients with a positive group B beta-hemolytic Streptococcus culture and 1.9% (8/420) among patients with a negative culture. Among the patients who underwent adequate prophylaxis, crystalline penicillin G was used in 51.9% (54/104), followed by cefazolin in 43.3% (45/104), ampicillin in 3.8% (4/104), and clindamycin in 1.0% (1/104). A model that included prematurity (p==0.001) proved to be an independent risk predictor of early neonatal sepsis [χ2 (1)==15.0, odds ratio: 16.9, 95% confidence interval: 4.7-61.6, p<0.001, Nagelkerke R2==0.157]. CONCLUSION: The prevalence of a positive culture for group B beta-hemolytic Streptococcus was high. However, the prevalence of early neonatal sepsis was low in pregnant women with both positive and negative group B beta-hemolytic Streptococcus cultures and in pregnant women with a positive culture who underwent both adequate and inadequate antibiotic prophylaxis. Prematurity proved to be an independent predictor of early neonatal sepsis, considering the entire study population.

Skin-to-skin contact and late-onset sepsis in newborns weighing up to 1.800g: a cohort study / 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 >174.7min/day (>2.9h/day) was relevant (p<0.001) for newborns who weighed >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 (>2.9h/day).

Resumo Objetivos: avaliar a associação entre o tempo para iniciar o primeiro contato pele a pele (CPP) e o tempo diário praticado com a taxa de sepse tardia em recém-nascidos ≤1.800g. Métodos: coorte multicêntrica realizada em unidades neonatais de três regiões geográficas brasileiras. O CPP foi registrado em ficha individual pela equipe e pais do recém-nascido. Dados maternos e neonatais foram obtidos por questionários aplicados às mães e em prontuários médicos. A análise dos dados foi realizada por algoritmo da árvore de classificação, que dividiu o conjunto de dados em subconjuntos mutuamente exclusivos que melhor descreveram a variável resposta. Resultados: 405 recém-nascidos participaram do estudo, com média de 31,3±2,7 semanas de idade gestacional e mediana de peso ao nascer 1.412g (IQ=1.164-1.605g). Realizar o primeiro CPP com até 137h de vida (≤5,7 dias) foi associado a menor taxa de sepse tardia (p=0,02) para recém-nascidos que fizeram CPP diário de 112,5 a 174,7 min/dia (1,9 a 2,9h/dia), com redução na taxa de sepse (39,3% para 27,5%). Além disso, a duração do CPP>174,7min/dia (>2,9h/dia) foi relevante (p<0,001) para os recém-nascidos >1.344g, com redução nesse desfecho (21,1% para 6%). Conclusões: o CPP mostrou-se importante para redução das taxas de sepse tardia em recém-nascidos pré-termo, especialmente quando realizado de forma oportuna (≤5,7 dias) e prolongada (>2,9h/dia).

Early-onset neonatal sepsis as a risk factor for peri-intraventricular hemorrhage in premature infants / Sepse precoce como fator de risco para hemorragia peri-intraventricular em prematuros

ABSTRACT Objective: To assess early-onset sepsis as a risk factor of peri-intraventricular hemorrhage in premature infants born at less than or equal to 34 weeks' gestation and admitted to a neonatal intensive care unit (NICU). Methods: This retrospective cohort study included premature patients born at less than or equal to 34 weeks' gestation who were admitted to the NICU of a tertiary hospital in southern Brazil, and born from January 2017 to July 2021. Data were collected from patients' medical records. Early-onset sepsis was measured according to the presence or absence of diagnosis within the first 72 hours of life, whereas the outcome, peri-intraventricular hemorrhage, was described as the presence or absence of hemorrhage, regardless of its grade. Results: Hazard ratios were calculated using Cox regression models. A total of 487 patients were included in the study, of which 169 (34.7%) had some degree of peri-intraventricular hemorrhage. Early-onset sepsis was present in 41.6% of the cases of peri-intraventricular hemorrhage, which revealed a significant association between these variables, with increased risk of the outcome in the presence of sepsis. In the final multivariate model, the hazard ratio for early-onset sepsis was 1.52 (95% confidence interval 1.01-2.27). Conclusion: Early-onset sepsis and the use of surfactants showed to increase the occurrence of the outcome in premature children born at less than or equal to 34 weeks' gestation. Meanwhile, factors such as antenatal corticosteroids and gestational age closer to 34 weeks' gestations were found to reduce the risk of peri-intraventricular hemorrhage.

RESUMO Objetivo: O objetivo do presente trabalho foi avaliar a sepse precoce como fator de risco para hemorragia peri-intraventricular (HPIV) em prematuros com 34 semanas ou menos, admitidos em Unidade de Terapia Intensiva (UTI) Neonatal. Métodos: Este estudo de coorte retrospectivo incluiu pacientes prematuros com 34 semanas ou menos, que receberam alta da UTI Neonatal de hospital terciário, no sul do Brasil, nascidos no período de janeiro de 2017 a julho de 2021. Os dados foram coletados por meio dos prontuários desses pacientes. A sepse precoce foi mensurada conforme a presença ou a ausência do diagnóstico nas primeiras 72 horas de vida. Já o desfecho, hemorragia peri-intraventricular, foi descrito conforme a presença ou ausência da hemorragia, independentemente do grau. Resultados: Hazard ratios (HR) foram calculados por meio de modelos de regressão de Cox. Foram incluídos no estudo 487 pacientes. Destes, 169 (34,7%) apresentaram algum grau de hemorragia peri-intraventricular. A sepse precoce esteve presente em 41,6% dos casos de hemorragia peri-intraventricular e apresentou associação significativa, elevando o risco do desfecho quando presente. No modelo multivariável final, o HR para a sepse precoce foi de 1,52 (intervalo de confiança de 95% — IC95% 1,01-2,27). Conclusão: Sepse precoce e uso de surfactante demonstraram aumentar a ocorrência do desfecho em crianças prematuras até 34 semanas, enquanto fatores como corticoide antenatal e idades gestacionais mais próximas a 34 semanas mostraram reduzir o risco de ocorrência hemorragia peri-intraventricular.

Argon inhalation attenuates systemic inflammation and rescues lung architecture during experimental neonatal sepsis.

PURPOSE: Neonatal sepsis is a systemic inflammatory infection common in premature infants and a leading cause of mortality. Argon is an emerging interest in the field of noble gas therapy. Neonates with severe sepsis are frequently mechanically ventilated creating an opportunity for inhalation therapy. We aimed to investigate argon inhalation as a novel experimental therapy in neonatal sepsis. METHODS: Sepsis was established in C57BL/6 neonatal mice by a lipopolysaccharide intraperitoneal injection on postnatal day 9. Septic pup mice were exposed to room air as well as non-septic controls. In the argon group, septic pup mice were exposed to argon (70% Ar, 30% O2) for 6 h in a temperature-controlled environment. RESULTS: At 6 h, survival was significantly enhanced when septic mice received argon compared to septic controls. Serum profiles of cytokine release were significantly attenuated as well as lung architecture restored. CONCLUSIONS: Our findings suggest that argon inhalation as a novel treatment for neonatal sepsis, reducing mortality and counteracting the acute systemic inflammatory response in the blood and preserving the architecture of the lung. This research can contribute to a paradigm shift in the treatment and outcome of neonates with sepsis.

Fibrinogen-to-Albumin Ratio in Neonatal Sepsis.

Background: Previous studies have established an association between fibrinogen-to-albumin ratio (FAR) and cancer, cardiovascular disease, and coronavirus disease 2019. However, no studies have investigated the relationship between FAR and neonatal sepsis. This study aims to evaluate the association of fibrinogen-to-albumin ratio with the presence and severity of sepsis in neonates. Methods: A total of 1292 neonates with suspected sepsis were enrolled in this study. Clinical and laboratory data were collected from electronic medical records. Neonates with final diagnosis with sepsis were divided into the sepsis group, The remaining neonates were divided into the control group. Neonates with sepsis were further categorized into mild (n = 312) and severe (n = 425) groups based on the severity of their condition. FAR was determined by dividing the plasma fibrinogen concentration (g/L) by the serum albumin concentration (g/L). The statistical analyses were conducted using the SPSS 26.0 statistical software package, as deemed appropriate. Results: FAR levels were significantly higher in neonates with sepsis compared to the control group. Additionally, a significant gradual increase in FAR was observed in the control, mild sepsis, and severe sepsis groups (P < 0.001). Correlation analysis showed that FAR had a positive correlation with PCT, CRP, and the length of hospital stay. Multiple logistic regression analysis showed that FAR was independently associated with the presence and severity of neonatal sepsis. Specifically, FAR was identified as an independent risk factor for both the presence of sepsis (OR = 8.641, 95% CI 5.708-13.080, P < 0.001) and severe sepsis (OR = 2.817, 95% CI 1.701-4.666, P < 0.001). Conclusion: FAR is significantly increased in neonates with sepsis and had a correlation with the severity of sepsis. Increased FAR was an independent predictor for the presence and severity of neonatal sepsis.

Serum calprotectin as a marker of neonatal sepsis: a hospital-based cross-sectional diagnostic study.

Background: Despite significant advances in neonatal care, neonatal sepsis remains a major contributor to mortality, morbidity, and protracted hospitalization. The development of early possible diagnostic indicators for newborn sepsis is critical. Since calprotectin participates in major biological processes, it could be a diagnostic marker for infection/inflammation. This study aimed to estimate serum calprotectin in neonates with clinical sepsis. In addition, we compared serum calprotectin with standard sepsis markers and serum procalcitonin to evaluate its diagnostic accuracy. Methods: A hospital-based cross-sectional diagnostic study of neonates identified with clinical sepsis using standard criteria was carried out. We compared estimated serum calprotectin levels to serum procalcitonin levels and conventional sepsis markers (leucocyte count, blood culture, immature to total neutrophil ratio, and C- reactive protein). We used SPSS version 25 to analyze the data. To examine diagnostic accuracy and determine a cut-off value for serum calprotectin, we used the receiver operating characteristics (ROC) curve. Results: Of the 83 subjects included, 36.5% (30/83) had blood culture positive status, the median value of serum calprotectin being 0.93 ng/ml (0.67 to 1.3). Respiratory, cardiovascular, and gastrointestinal instabilities were present in 67.5% (56/83), 59% (49/83), and 50.1% (42/83) cases, respectively. The median values of serum calprotectin, procalcitonin, TLC, and I/T ratio between neonates withpositive blood culturesand negative culturesdid not differ significantly.. On ROC, calprotectin was not predictive for blood culture positivity (sensitivity: 50%; specificity: 44% at 0.83 ng/ml of serum calprotectin) and C-reactive protein (CRP) levels (sensitivity: 57%; specificity: 67% at serum calprotectin levels of 0.89 ng/ml). However, compared with serum procalcitonin, serum calprotectin at 1.2 ng/ml had sensitivity and specificity of 60% and 73%, respectively. Conclusions: Serum calprotectin did not show a distinct advantage over the existing sepsis markers. Serum calprotectin level at 1.2 ng/ml had a sensitivity and specificity of 60% and 73%, respectively, compared to serum procalcitonin in detecting neonatal sepsis.

Decreased incidence of late-onset sepsis during the SARS-CoV-2 pandemic in Italy: a multicentric study on a cohort of infants requiring major surgery.

Changes in the organization of the clinical care wards, requested by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, have influenced the environmental circulation of other pathogens. The implementation of prevention procedures may have led to a decrease in the incidence of healthcare-associated infections. We aimed to investigate the impact of prevention and control measures for preventing the COVID-19 spread on the incidence of bacterial sepsis and invasive fungal infections in neonates and infants requiring major surgery. We compared the incidence of bacterial and fungal sepsis and their risk factors observed before the SARS-CoV-2 pandemic (from 01/10/2018 to 29/02/2020) with those observed during the pandemic (from 01/03/2020 to 07/05/2021) in 13 level III Neonatal Intensive Care Units in Italy, through a secondary analysis of data, collected during a prospective multicenter study (REF). The patients enrolled were infants within three months of life, hospitalized in the two periods in the participating centers to undergo major surgery. Among 541 enrolled patients, 324 (59.9%) were born in the pre-pandemic period and 217 (40.1%) during the pandemic. The incidence density (ID) of any infection in the pre-pandemic period was 16.0/1000 patient days versus 13.6/1000 patient days in the pandemic period (p < 0.001). One hundred and forty-five (145/324; 44.8%) patients developed at least one episode of bacterial sepsis in the pre-pandemic period, versus 103/217 (31.8%) patients, during the pandemic (p = 0.539). Concerning fungal sepsis, 12 (3.7%) patients had one episode in the pre-pandemic period versus 11 (5.1%) patients during the pandemic (p = 0.516). The most significant differences observed in the use of healthcare procedures were the reduction of CVC days, the reduced use of antibiotics pre-surgery, and that of proton pump inhibitors during the SARS-CoV-2 pandemic compared with the previous period. CONCLUSIONS: In our cohort of patients with major surgical needs, the reduction of CVC days, pre-surgery antibiotics administration, and current use of proton pump inhibitors, during the SARS-CoV-2 pandemic, led to a decrease in the incidence of late-onset sepsis. WHAT IS KNOWN: • Most cases of late-onset sepsis in neonates are referred to as central line-associated bloodstream infections. • In adults, the COVID-19 outbreak negatively influenced healthcare-associated infection rates and infection clusters within hospitals. WHAT IS NEW: • In neonates and infants undergoing major surgery the incidence density of infections was lower in the pandemic period than before. • The most significant differences observed in the use of healthcare procedures were the reduction of CVC days, the reduced use of antibiotics before surgery, and that of proton pump inhibitors during the pandemic compared with previously.

Evaluation of Haematological Parameters and Uric Acid in the Diagnosis of Late Onset Neonatal Sepsis.

Introduction A number of parameters studied in a whole blood count can be helpful in the diagnosis of neonatal sepsis. The platelet/lymphocyte ratio (PLR) is a systemic inflammatory marker in early sepsis and has been used as a diagnostic indicator in cardiovascular events and cancer. Being one of the major antioxidants in human biological fluids, serum uric acid is responsible for neutralising free radicals. The red cell distribution width/platelet ratio (RPR) is a diagnostic marker in adult inflammatory diseases. The objective of our study is to investigate the relationship of late neonatal sepsis with whole blood count parameters and serum uric acid levels. Materials and methods Newborns older than postnatal three days who had clinical and laboratory findings of sepsis were included in the study. The study included 140 newborns who were divided into three groups, 53 in the culture-proven late sepsis group, 47 in the clinical sepsis group, and 40 in the healthy control group. The whole blood count parameters and serum uric acid levels were examined in both the clinical sepsis and proven sepsis patients at the time when they were diagnosed with sepsis. Results The birth week was significantly lower in the evidenced and clinical sepsis patients compared to the healthy control group. Development of late sepsis was significantly higher in the male gender than in healthy controls. Serum uric acid levels were significantly higher in proven or clinical sepsis than in healthy controls. The level of serum uric acid (3.77±1.6) in proven sepsis was significantly higher than the control group (2.83±1.1). The uric acid level had an area under the curve (AUC) 0.552-0.717, 35% sensitivity, 95% specificity, 94.6% positive predictive value (PPV), and 36.9% negative predictive value (NPV) in the diagnosis of proven and clinical late sepsis. Neutrophil/lymphocyte ratio (NLR) was significantly higher in proven sepsis than in healthy newborns and was higher in the clinical sepsis group than in the proven sepsis group (p: 0.002). While the mean eosinophil value was 618.5±472.1 in proven sepsis, it was 549.3±294.9 in the control group and there was a statistically significant difference between the two groups (p: 0.036). Conclusion In late-onset neonatal sepsis, the NLR level was higher, and the eosinophil level was lower in the clinical sepsis patients than in healthy newborns. We believe that a higher level of serum uric acid in sepsis is effective in the early diagnosis of patients who also had other clinical findings of sepsis.

Cultural patterns and outcome of umbilical cord care among caregivers in Africa: a systematic review.

The third leading cause of death in infants under 1-month-old is neonatal sepsis. Following the severing of the umbilical cord, bacterial infection may result in newborn sepsis and mortality. The objective of this review on cultural patterns and umbilical cord-care outcomes is to evaluate present practices and create a case for developing and implementing novel cord-care regimens in Africa. Materials and methods: In order to find published studies on cultural patterns and outcomes of umbilical cord care among caregivers in Africa from January 2015 to December 2021, we conducted a systematic literature search across six computerized bibliographic databases: Google Scholar, POPLINE, PubMed, Web of Science, Science Direct, and Scopus. As a result, a narrative synthesis of quantitative and qualitative data was employed to summarize the data from the included research. Results: There were 17 studies included in this review with 16 out of the 17 studies having a total of 5757 participants. The odds of neonatal sepsis were 13 times higher among infants whose caregivers had improper hygiene compared with those who had proper hygiene. The outcome of cord management showed that the majority (75.1%) of the umbilical cords were infected. Majority of the included studies (n=13) show that the respondents (caregivers) had a low level of knowledge and practice. Conclusion: This systematic review reveals that unsafe umbilical cord-care practices remained prevalent in some African regions. Home delivery is still a prevalent practice in some communities and inappropriate umbilical cord cleaning practices were common findings.

Bioinformatic Analysis and Machine Learning Methods in Neonatal Sepsis: Identification of Biomarkers and Immune Infiltration.

The disease neonatal sepsis (NS) poses a serious threat to life, and its pathogenesis remains unclear. Using the Gene Expression Omnibus (GEO) database, differentially expressed genes (DEGs) were identified and functional enrichment analyses were conducted. Three machine learning algorithms containing the least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE), and random forest (RF) were applied to identify the optimal feature genes (OFGs). This study conducted CIBERSORT to present the abundance of immune infiltrates between septic and control neonates and assessed the relationship between OFGs and immune cells. In total, 44 DEGs were discovered between the septic and control newborns. Throughout the enrichment analysis, DEGs were primarily related to inflammatory signaling pathways and immune responses. The OFGs derived from machine learning algorithms were intersected to yield four biomarkers, namely Hexokinase 3 (HK3), Cystatin 7 (CST7), Resistin (RETN), and Glycogenin 1 (GYG1). The potential biomarkers were validated in other datasets and LPS-stimulated HEUVCs. Septic infants showed a higher proportion of neutrophils (p < 0.001), M0 macrophages (p < 0.001), and regulatory T cells (p = 0.004). HK3, CST7, RETN, and GYG1 showed significant correlations with immune cells. Overall, the biomarkers offered promising insights into the molecular mechanisms of immune regulation for the prediction and treatment of NS.