Alteration of Maternal Serum Ferritin in Pregnancy and Maternal-fetal Infections: A retrospective cohort study.

Objectives: To investigate the association of altered serum ferritin during pregnancy with chorioamnionitis and neonatal sepsis. Methods: This retrospective cohort study included 78,521 pregnant women who attended antenatal check-ups at maternal and child health centers in Fujian Province, China. Study lasted from January 2014 to January 2019. A total of 59,812 pregnant women were followed up. Patients with suspected infection before the delivery were selected and divided into the chorioamnionitis and non-chorioamnionitis groups according to placental pathology. Differences in late and early pregnancy serum ferritin between the two groups were compared. Multiple logistics regression was used to adjust for confounding factors and to analyze the association between serum ferritin changes and pregnancy outcomes. Importance of altered serum ferritin during pregnancy was assessed by receiver operating characteristic (ROC) curve and net reclassification index (NRI). Results: Clinical records of 8506 pregnant women were included in the study. there were 1010 (11.9%) cases of confirmed chorioamnionitis and 263 (3.1%) cases of neonatal sepsis. There was a significant difference in maternal serum ferritin changes between the groups with and without chorioamnionitis. No significant difference was detected in cases with or without neonatal sepsis. Multiple logistic regressions, corrected for confounding factors yielded similar conclusions. Maternal serum ferritin difference NRI 12.18% (p = 0.00014) was similar to the ROC results in predicting the occurrence of chorioamnionitis. Conclusion: Differential serum ferritin during pregnancy may predict chorioamnionitis but does not correlate well with neonatal sepsis.

Antibiotic Management for Early-Onset Sepsis in Neonates With Gestational Ages of ≥ 34 Weeks: The Kaiser Sepsis Calculator Versus the 2010 CDC Guidelines.

INTRODUCTION: The traditional approach to neonatal early-onset sepsis (NEOS) management, involving maternal risk factors and nonspecific neonatal symptoms, usually leads to unnecessary antibiotic use. This study addresses these concerns by evaluating the Kaiser sepsis calculator (KSC) in guiding antibiotic therapy for NEOS, especially in high-incidence facilities (over 4/1,000 live births), by comparing it against the 2010 Centers for Disease Control and Prevention (CDC) guidelines for neonates ≥34 weeks with suspected sepsis, thereby emphasizing its implications for personalized patient care. METHODS: This is a prospective observational study. All neonates of 34 gestational weeks or more, presenting with either maternal risk factors or sepsis symptoms within 12 hours of birth, were included in the study. The analysis focused on antibiotic recommendations by the 2010 CDC guidelines versus those by the KSC at presumed (0.5/1,000) and actual (16/1,000) sepsis incidence rates. RESULTS: NEOS was identified in 14 cases (14.1%). Compared to the KSC, at an incidence rate of 16 per 1,000, the KSC resulted in a significant 32.3% reduction in antibiotic treatment (74 cases (74.7%) vs. 42 cases (42.4%), respectively; p < 0.001). The calculator advised immediate antibiotic utilization for 13 out of 14 (92.9%) diagnosed cases, suggesting further evaluation for the remaining cases. When a presumed incidence of 0.5/1,000 was applied, the KSC indicated antibiotics less frequently than when using the actual rate of 16/1,000 (p<0.001) with two missed NEOS cases. CONCLUSIONS: Using the KSC led to a decrease of 32 cases (32.3%) in unnecessary antibiotic prescriptions compared to adherence to 2010 CDC guidelines. However, setting a presumed incidence below the actual rate risked missing NEOS. The calculator was effective when actual local incidence rates were used, ensuring no missed cases needing antibiotics.

Comparison of the accuracy of hematological parameters in the diagnosis of neonatal sepsis: a network meta-analysis.

BACKGROUND: Currently, there are hundreds of hematological parameters used for rapid diagnosis of neonatal sepsis, but there is no network meta-analysis to compare the diagnostic efficacy of these parameters. METHODS: We searched for literature on the diagnostic neonatal sepsis and selected 20 of the most common parameters to compare their diagnostic efficacy. We used Bayesian network meta-analysis, Frequentist network meta-analysis, and individual traditional diagnostic meta-analysis to analyze the data and verify the stability of the results. Based on the above analysis, we ranked the diagnostic efficacy of 20 parameters and searched for the optimal indicator. We also conducted subgroup analysis based on different designs. GRADE was used to evaluate the quality of evidence. RESULTS: 311 articles were included in the analysis, of which 206 articles were included in the network meta-analysis. Bayesian models fond the top three of the advantage index were P-SEP, SAA, and CD64. In Individual model, P-SEP, SAA, and CD64 had the best sensitivity; ABC, SAA, and P-SEP had the best specificity. Frequentist model showed that CD64, P-SEP, and IL-10 ranked in the top three for sensitivity, while P-SEP, ABC, and I/M in specificity. Overall, P-SEP, SAA, CD64, and PCT have good sensitivity and specificity among all the three methods. The results of subgroup analysis were consistent with the overall analysis. All evidence was mostly of moderate or low quality. CONCLUSIONS: P-SEP, SAA, CD64, and PCT have good diagnostic efficacy for neonatal sepsis. However, further studies are required to confirm these findings.

Corrigendum: Xenon attenuated neonatal lipopolysaccharide exposure induced neuronal necroptosis and subsequently improved cognition in juvenile rats.

[This corrects the article DOI: 10.3389/fphar.2022.1002920.].

Neonatal intestinal colonization of Streptococcus agalactiae and the multiple modes of protection limiting translocation.

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a predominant pathogen of neonatal sepsis, commonly associated with early-onset neonatal sepsis. GBS has also been associated with cases of late-onset sepsis potentially originating from the intestine. Previous findings have shown GBS can colonize the infant intestinal tract as part of the neonatal microbiota. To better understand GBS colonization dynamics in the neonatal intestine, we collected stool and milk samples from prematurely born neonates for identification of potential pathogens in the neonatal intestinal microbiota. GBS was present in approximately 10% of the cohort, and this colonization was not associated with maternal GBS status, delivery route, or gestational weight. Interestingly, we observed the relative abundance of GBS in the infant stool negatively correlated with maternal IgA concentration in matched maternal milk samples. Using a preclinical murine model of GBS infection, we report that both vertical transmission and direct oral introduction resulted in intestinal colonization of GBS; however, translocation beyond the intestine was limited. Finally, vaccination of dams prior to breeding induced strong immunoglobulin responses, including IgA responses, which were associated with reduced mortality and GBS intestinal colonization. Taken together, we show that maternal IgA may contribute to infant immunity by limiting the colonization of GBS in the intestine.

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.

An Observational Study on C-Reactive Protein to Platelet Ratio in Neonatal Sepsis.

BACKGROUND: Neonatal sepsis is a serious medical condition affecting many individuals in the developing world. C-reactive protein (CRP) level in serum and platelet counts have been reported to have role in diagnosis of neonatal sepsis. OBJECTIVE: To evaluate the CRP to Platelet ratio (CPR) in relation to time and blood culture reports in neonatal sepsis patients from a tertiary care centre in the Marathwada region of Maharashtra. METHODS: The present observational study was conducted at the level III Neonatal Intensive Care Unit of a tertiary care centre in Aurangabad city of Marathwada region in Maharashtra from September 2022 to July 2023. The study included 120 neonates (delivered after completion of 28-42 weeks of gestation) with clinical/culture-positive sepsis. The newborns of seropositive mothers, neonates delivered in other hospitals, babies with congenital dysmorphic features, and babies requiring surgical procedures were excluded from the study. Blood samples for complete blood count (CBC) and CRP were collected on days 1, 3 and 5. Blood cultures were sent on day 1 of illness. Repeated measures ANOVA was used to compare the parameters of CPR, CRP, and platelet count in blood culture-positive and blood culture-negative neonatal sepsis patients on days 1, 3 and 5. RESULTS: Blood culture was positive in 37 (30.8%) cases. A repeated measures ANOVA showed a significant overall difference in the CPR across days 1, 3, and 5 (p = 0.006). The CPR was significantly higher in culture-positive neonates compared to culture-negative neonates (p = 0.042). CONCLUSION: Higher CPR in blood culture-positive neonates compared to blood culture-negative neonates supports the role of CPR in the diagnosis and management of neonatal sepsis.

Characteristics of Neonatal Sepsis and Predictive Values of Polyfunctional Assessment of Umbilical Cord Neutrophils Based on Single Cell Proteomic Secretion.

The early diagnosis of neonatal sepsis is crucial as it remains a prevalent cause of neonatal mortality. In this study, we conducted an analysis on the clinical data and detection indicators of 22 cases with sepsis and 62 cases without sepsis among neonates. Our findings indicate that the clinical signs observed in neonates with sepsis lack specificity. In addition, the commonly used clinical inflammatory indicators (such as leukocyte count, neutrophil-to-lymphocyte ratio [NLR], C-reactive protein [CRP], procalcitonin) exhibit limited sensitivity and specificity. Furthermore, the current clinical measures lack the assessment of inflammatory factors. Therefore, in order to enhance the accuracy of early sepsis diagnosis in neonates, we have employed a novel microfluidic-based single-cell technology platform for the analysis of 32 cytokines secreted by neutrophils at the individual cell level under various toxin stimulation conditions. We have further investigated and compared the disparities in single-cell protein secretomics between umbilical cord blood neutrophils and healthy adult peripheral neutrophils within an in vitro sepsis model. Our findings indicate that in a resting state UCB neutrophils exhibited lower polyfunctionality compared with healthy adult blood neutrophils, and notable variations in cytokine secretion profiles were detected between the two groups. However, the polyfunctionality of UCB neutrophils significantly increased and surpassed that of healthy adult neutrophils when exposed to alpha-hemolysin or lipopolysaccharide. UCB neutrophils secreted a wide range of chemokines and inflammatory factors, among which GM-CSF and IL-18 were the most significant. Furthermore, we initially categorized the functional subgroups of neutrophils by considering the secretion of five primary cytokines by neutrophils (GM-CSF, IL-18, IL-8, MIP-1ß, and MIF). The current study, for the first time, examined in detail the heterogeneity of protein secretion and the functional diversity of UCB neutrophils stimulated by different antigens. Moreover, new insight into neonatal sepsis, early diagnosis, and wider clinical applications of UCB neutrophils are provided by these data.

Enhancing Early Detection of Sepsis in Neonates through Multimodal Biosignal Integration: A Study of Pulse Oximetry, Near-Infrared Spectroscopy (NIRS), and Skin Temperature Monitoring.

Sepsis continues to be challenging to diagnose due to its non-specific clinical signs and symptoms, emphasizing the importance of early detection. Our study aimed to enhance the accuracy of sepsis diagnosis by integrating multimodal monitoring technologies with conventional diagnostic methods. The research included a total of 121 newborns, with 39 cases of late-onset sepsis, 35 cases of early-onset sepsis, and 47 control subjects. Continuous monitoring of biosignals, including pulse oximetry (PO), near-infrared spectroscopy (NIRS), and skin temperature (ST), was conducted. An algorithm was then developed in Python to identify early signs of sepsis. The model demonstrated the capability to detect sepsis 6 to 48 h in advance with an accuracy rate of 87.67 ± 7.42%. Sensitivity and specificity were recorded at 76% and 90%, respectively, with NIRS and ST having the most significant impact on predictive accuracy. Despite the promising results, limitations such as sample size, data variability, and potential biases were noted. These findings highlight the critical role of non-invasive biosensing methods in conjunction with conventional biomarkers and cultures, offering a strong foundation for early sepsis detection and improved neonatal care. Further research should be conducted to validate these results across different clinical settings.

16S rDNA Sequencing for Bacterial Identification in Preterm Infants with Suspected Early-Onset Neonatal Sepsis.

BACKGROUND: The high prevalence of suspected early-onset neonatal sepsis among preterm infants leads to immediate antibiotic administration upon admission. Notably, most blood cultures for suspected early-onset neonatal sepsis do not yield a causative pathogen. This study aimed to assess polymerase chain reaction (PCR) targeting the variable region V4 of the 16S ribosomal gene (16S rDNA) and Sanger sequencing for bacterial identification in preterm infants with suspected early-onset neonatal sepsis. METHODS: Therefore, this prospective study was conducted. Preterm infants with suspected early-onset neonatal sepsis were included in this study. The three groups were formed based on the risk of infection and clinical sepsis. Blood samples were collected upon admission to the neonatal unit for culture and molecular analysis. PCR amplification and subsequent Sanger sequencing of the V4 region of the 16S rDNA were performed. RESULTS: Twenty-eight patients were included in this study. Blood cultures were negative in 100% of the patients. Amplification and sequencing of the V4 region identified bacterial genera in 19 patients across distinct groups. The predominant taxonomically identified genus was Pseudomonas. CONCLUSIONS: Amplifying the 16S rDNA variable region through PCR and subsequent Sanger sequencing in preterm neonates with suspected early-onset neonatal sepsis can enhance the identification of microbial species that cause infection, especially in negative cultures.

Time to Positivity of Blood Culture as a Predictor of Causative Pathogens and Survival in Neonatal Sepsis: A Retrospective Cohort Study from Indonesia.

Objectives: In the blood culture procedure for neonatal sepsis, time to positivity (TTP) reflects the pathogenic bacterial load and the time required for empirical antibiotic regimen administration prior to definitive treatment. This study aims to identify the differences in TTP among causative pathogens and its predictive value for the overall survival of neonates with sepsis at a tertiary healthcare center in Indonesia. Methods: A retrospective cohort study was conducted from January 2020 to August 2022 at Dr. Soetomo General Hospital, Surabaya, Indonesia. Neonates with blood culture-proven neonatal sepsis were included in the analysis. TTP was defined as the time between the acceptance of a blood culture specimen from the neonatal intensive care unit and reports of positive culture growth by the laboratory. Results: Across 125 cases, the median TTP was 58.1 hours (IQR = 24.48). Blood cultures were positive within 48 hours for 41.6% of cases, 72 hours for 86.4%, and 96 hours for 98.4%. A significantly shorter TTP was exhibited by the three major gram-negative organisms (Klebsiella pneumoniae,Acinetobacter baumannii,Enterobacter cloacae) compared to coagulase-negative Staphylococci. The neonatal sepsis mortality rate was 49.6% during the study period. In the Cox multivariate regression model, a shorter TTP was an independently predicted mortality in the entire cohort (hazard ratio (HR) = 0.985, 95% CI: 0.973-0.998) and the gram-negative sepsis cohort group (HR = 0.983, 95% CI: 0.968-0.999). Conclusions: TTP predicts different causative pathogens and the overall survival of neonatal sepsis cases at a tertiary healthcare facility in Indonesia.

Factors associated with neonatal sepsis among neonates admitted in Kibungo Referral Hospital, Rwanda.

More than one million neonatal deaths occur every year worldwide, of which 99% take place in low-income countries. In Rwanda, nearly 71% of neonatal deaths are preventable and among these, 10% are due to neonatal sepsis. Nevertheless, limited information exists on neonatal sepsis and its associated factors in Rwanda. The objectives of the study were to find prevalence and factors associated with neonatal sepsis among neonates admitted in Kibungo Referral Hospital, Ngoma District, Rwanda. We used a retrospective cross-sectional study design reviewing a subset of neonatal, maternal and laboratory records from Kibungo Hospital in 2017. Data were reviewed and collected from March to May, 2018. Logistic regression and odds ratios were calculated to identify the factors associated with neonatal sepsis at 95% CI, p < 0.05. Of the 972 total neonates' medical records from 2017, we randomly selected 422 of which 12.8% (n = 54) had neonatal sepsis. When blood cultures were positive, 62% grew Klebsiella pneumoniae. Among neonates with sepsis, 38 (70%) recovered while 16 (30%) died. Neonatal sepsis was strongly associated with neonatal age less than or equal to three days (aOR: 2.769, 95% CI 1.312-5.843; p = 0.008); and gestational age less than 37 weeks (aOR: 4.149; CI 1.1878-9.167; p ≤ 0.001). Increased use of blood cultures including sensitivity testing, routine surface cultures of the neonatology and maternity wards facilities, and systematic ward cleaning are all important approaches to prevent and treat neonatal infections in additional to regular neonatal sepsis evaluations.

Loop-mediated isothermal amplification (LAMP) assay for early on-site detection of Group B Streptococcus infection in neonatal sepsis blood sample.

BACKGROUND: Neonatal sepsis, often attributed to Group B Streptococcus (GBS) infection, poses a critical health risk to infants, demanding rapid and accurate diagnostic approaches. Existing diagnostic approaches are dependent on traditional culture methods, a process that requires substantial time and has the potential to delay crucial therapeutic assessments. METHODS: This study introduces an innovative Loop-Mediated Isothermal Amplification (LAMP) assay for the early on-site detection of GBS infection from neonatal sepsis blood samples. To develop a LAMP assay, the primers are designed for the selective targeting of a highly conserved segment within the cfb gene encoding the CAMP factor in Streptococcus agalactiae ensuring high specificity. RESULTS: Rigorous optimization of reaction conditions, including temperature and incubation time, enhances the efficiency of the LAMP assay, enabling rapid and reliable GBS detection within a short timeframe. The diagnostic efficacy of the LAMP assay was evaluated using spiked blood samples by eliminating the DNA extraction step. The simplified colorimetric LAMP assay has the capability to detect S. agalactiae in a neonatal blood sample containing 2 CFU/mL during sepsis. Additionally, the LAMP assay effectively detected S. agalactiae in both the standard and spiked blood samples, with no detectable interference with blood. CONCLUSION: This optimised LAMP assay emerges as a promising tool for early GBS detection, offering a rapid and accurate on-site solution that has the potential to inform timely interventions and improve outcomes in neonatal sepsis cases.

PeRinatal, neOnatal, and Maternal OuTcomEs with azithromycin prophylaxis in pregnancy and labour (PROMOTE-PROPHYLAXIS): systematic review and meta-analysis.

Background: Initial randomised controlled trials (RCTs) showed that prophylactic azithromycin in pregnant women improved maternal and neonatal outcomes; however, the recent evidence did not show any benefit to neonatal survival. There is conflicting evidence over the role of azithromycin prophylaxis in antenatal and intrapartum periods. We explored whether azithromycin prophylaxis in pregnant women improves maternal and neonatal outcomes. Methods: For this systematic review and meta-analysis registered on PROSPERO [CRD42023411093], we searched seven databases (PubMed, Scopus, Embase, Cochrane Library, EBSCOHost, ProQuest, and Web of Science) and clinical trial registries until 04/23/2024, for RCTs evaluating antenatal/intrapartum azithromycin prophylaxis against placebo/routine care in pregnant women. The primary outcome was neonatal mortality. Intrapartum and antenatal administration were assessed separately. We used random-effects meta-analysis. The risk of bias was assessed using the Cochrane RoB 2 tool. The GRADE approach was used to evaluate the certainty of the evidence. Findings: Screening 2161 records retrieved 20 RCTs (56,381 participants). Intrapartum azithromycin may make little or no difference to neonatal mortality [5 RCTs, 44,436 participants; Risk Ratio (RR): 1.02, 95% CI 0.86-1.20, I 2  = 0%, very low certainty], and maternal mortality [3 RCTs, 44,131 participants, RR: 1.26, 0.65-2.42, I 2  = 0%, low certainty]. Similarly, antenatal azithromycin may have little or no effect on neonatal mortality [3 RCTs; 5304 participants; RR: 0.74, 0.35-1.56, I 2  = 43%, very-low certainty] and maternal mortality [3 RCTs; 8167 participants RR: 1.62, 0.67-3.91, I 2  = 0%, low certainty]. There is no data on long-term adverse outcomes and antimicrobial resistance. Interpretation: Low to very low certainty evidence suggests that intrapartum or antenatal azithromycin prophylaxis in pregnant women might not reduce maternal or neonatal mortality. Funding: None.

The diagnostic performance of mean neutrophil volume in neonatal sepsis: A systematic review and meta-analysis.

BACKGROUND: There is a need for reliable diagnostic tests for early identification of sepsis to prevent neonatal mortality and antibiotic misuse. During sepsis, many immature neutrophils came into the bloodstream, altering the mean neutrophil volume (MNV) shown in the previous studies. OBJECTIVES: To summarize the diagnostic performance of mean neutrophil volume (MNV) in neonatal sepsis from the published literature. METHOD: Databases such as PubMed, Scopus, and Web of Science were searched from January 1990 to April 2023 for studies reporting MNV as a diagnostic test in neonatal sepsis. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve of MNV were estimated with reference blood culture-positive sepsis and clinical sepsis for meta-analysis. RESULT: The diagnostic performance of MNV was analyzed in 1685 neonates, including 829 septic and 856 non-septic neonates, from six prospective studies. The pooled sensitivity and specificity of MNV were 0.87 and 0.75, respectively, for neonatal sepsis; the DOR was 20.01 (95% CI: 5.90-67.82); and the AUC of the SROC for MNV was 0.81 (95% CI: 0.69-0.88). Higgins I2 was 92.1% (95% CI: 85.5%-95.7%). The diagnostic performance of MNV was better during sub-group analysis of studies reporting culture-positive sepsis (DOR 85.61). CONCLUSION: The diagnostic performance of MNV is moderate for neonatal sepsis. As the evidence originated from a small number of studies with marked heterogeneity, further large-scale diagnostic accuracy studies are recommended to resolve heterogeneity in the future.

Frozen Section of Placental Membranes and Umbilical Cord: A Valid Diagnostic Tool for Early-Onset Neonatal Sepsis Management.

Early-onset neonatal sepsis (EONS), a serious infection in newborns within 3 days, is challenging to diagnose. The current methods often lack accuracy, leading to unnecessary antibiotics or delayed treatment. This study investigates the role of the frozen section examination of placental membranes and umbilical cord (FSMU) to improve EONS diagnosis in the daily lab practice. This retrospective study reviewed data from 59 neonates with EONS risk factors who underwent FSMU according to our institutional protocol. Concordance between the FSMU and the Final Pathological Report (FPR) was assessed. The FSMU demonstrated a high concordance (Kappa = 0.88) for funisitis diagnosis, with excellent accuracy (98.3%). A moderate concordance was observed for chorioamnionitis stage and grade. The FSMU shows promise as a rapid and accurate tool for diagnosing EONS, particularly for funisitis. This study suggests that the FSMU could be a valuable tool for EONS diagnosis, enabling a more judicious antibiotic use and potentially improving outcomes for newborns.

Outcomes of interventions in neonatal sepsis: A systematic review of qualitative research.

BACKGROUND: While a systematic review exists detailing neonatal sepsis outcomes from clinical trials, there remains an absence of a qualitative systematic review capturing the perspectives of key stakeholders. OBJECTIVES: Our aim is to identify outcomes from qualitative research on any intervention to prevent or improve the outcomes of neonatal sepsis that are important to parents, other family members, healthcare providers, policymakers, and researchers as a part of the development of a core outcome set (COS) for neonatal sepsis. SEARCH STRATEGY: A literature search was carried out using MEDLINE, EMBASE, CINAHL, and PsycInfo databases. SELECTION CRITERIA: Publications describing qualitative data relating to neonatal sepsis outcomes were included. DATA COLLECTION AND ANALYSIS: Drawing on the concepts of thematic synthesis, texts related to outcomes were coded and grouped. These outcomes were then mapped to the domain headings of an existing model. MAIN RESULTS: Out of 6777 records screened, six studies were included. Overall, 19 outcomes were extracted from the included studies. The most frequently reported outcomes were those in the domains related to parents, healthcare workers and individual organ systemas such as gastrointestinal system. The remaining outcomes were classified under the headings of general outcomes, miscellaneous outcomes, survival, and infection. CONCLUSIONS: The outcomes identified in this review are different from those reported in neonatal sepsis clinical trials, thus highlighting the importance of incorporating qualitative studies into COS development to encapsulate all relevant stakeholders' perspectives.

Impacts of COVID-19 pandemic on culture-proven sepsis in neonates.

Objective: To assess the effects of COVID-19 pandemic on the epidemiology of neonatal sepsis and the antibiotic resistance profiles of pathogens involved. Methods: This retrospective cohort study analyzed infants diagnosed with culture-proven sepsis at the neonatal department of a tertiary children's hospital in East China from January 2016 to December 2022. We compared the clinical and microbiological characteristics of neonatal sepsis cases between the pre-pandemic Phase I (2016-2019) and during the COVID-19 pandemic Phase II (2020-2022). Results: A total of 507 infants with 525 sepsis episodes were included, with 343 episodes in Phase I and 182 in Phase II. The incidence of early-onset sepsis (EOS) was significantly lower during Phase II (p < 0.05). Infants in Phase II had lower gestational ages and birth weights compared to Phase I. Clinical signs such as mottled skin, severe anemia, thrombocytopenia were more prevalent in Phase II, alongside a higher incidence of complications. Notably, necrotizing enterocolitis (NEC) (p < 0.05) and meningitis (p < 0.1) occurred more frequently during Phase II. Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) were the predominant pathogens isolated from infants of death and cases with complications. A significant decrease in the proportion of K. pneumoniae was observed in Phase II, alongside increased antibiotic resistance in both E. coli and K. pneumoniae. The period of the COVID-19 pandemic (Phase II) was identified as an independent risk factor for complications in infants with neonatal sepsis. Conclusion: COVID-19 pandemic response measures correlated with a decrease in EOS and an increase in neonatal sepsis complications and antibiotic resistance.

Myocardial performance imaging for the early identification of cardiac dysfunction in neonates with sepsis.

PURPOSE: The assessment of cardiac performance in septic new-borns is crucial for detecting hemodynamic instability and predicting outcome. The aim of the study is to assess myocardial performance in neonates with sepsis for the early identification of cardiac dysfunction. PATIENTS AND METHODS: A case control study was carried out from September 2022 to May 2023 at the Neonatal Intensive care unit, Kasturba Medical College, Manipal. A total of 68 neonates were included in the study, with 33 females and 35 males. The study population was further subdivided into 3 groups namely preterm septic neonates (n = 21), term septic neonates (n = 10) and non-septic healthy controls (n = 37). The cardiac structure and function were assessed using conventional method, Tissue Doppler imaging (Sm) and speckle tracking echocardiography (GLS). The study was approved by the Institutional Ethics Committee at Kasturba Medical College, Manipal (approval number IEC: 90/2022). The CTRI registration number for the study is CTRI/2022/09/045437 and was approved on September 12, 2022. Prior to the neonate's enrolment, informed consent was obtained from their mothers or legal guardians. RESULTS: Out of the total 68 neonates, 31 were cases and 37 were controls which included 33 females and 35 males. LV systolic function was not statistically significant between cases and controls. E/A ratio of the mitral valve was significantly lower in septic newborns than in healthy neonates. (1.01 ± 0.35 vs 1.18 ± 0.31, p < 0.05) preterm neonates showed significantly lower Lateral E' and RV E' velocities than term neonates. TAPSE was significantly lower in septic preterm neonates. (8.61 ± 1.28 vs. 10.7 ± 2.11, p < 0.05) No significant difference was noted in the Myocardial Performance Index between septic neonates and healthy neonates. LV Global Longitudinal Strain was slightly lower in preterm septic neonates than in term neonates with sepsis. CONCLUSION: Septic newborns are associated with LV diastolic dysfunction, RV systolic dysfunction and substantially higher pulmonary systolic pressures.