TREM-1: A potential prognostic marker in newborns with late-onset sepsis.

Late-onset sepsis (LOS), which occurs 72 hours after birth, remains an important cause of mortality and morbidity in the neonatal intensive care unit (NICU). Differences in infant populations and the complexity of care at various NICU levels may result in varying bacteriological profiles and antibiotic susceptibility patterns. The objective of the current study was to determine and compare the bacteriological profiles, antibiotic susceptibility, and risk factors for LOS in levels III and IV NICU within a single hospital system. This was a retrospective study of infants with LOS and positive blood cultures, admitted to levels III and IV NICUs between 2012 and 2021. Of the 173 infants included in our study, 105 were admitted to the level IV NICU and 68 to the level III NICU. Infants in the level III NICU had a lower gestational age and birth weight at the time of LOS. Seventy percent of the infants had a central line. Gram-positive organisms were responsible for the vast majority of infections (75%), with coagulase-negative Staphylococcus (CoNS) being the most common bacteria in both units. Gram-negative bacteria were more frequently isolated from the level IV NICU (36.2%) compared to the level III NICU (8.8%). Escherichia coli (E. coli) and Enterobacter sp. were the most frequently isolated gram-negative bacteria. All gram-positive bacteria were susceptible to vancomycin, and all gram-negative bacteria were susceptible to meropenem. The prevalent bacteriological profile and antibiotic susceptibility patterns in the NICU should guide the choice of empiric antibiotics for LOS. It is important to monitor sepsis and antimicrobial resistance patterns in the NICU and implement risk-specific strategies to reduce the burden of LOS. · LOS in NICUs is predominantly caused by gram-positive bacteria, mainly CoNS.. · Higher frequency of gram-negative bacteria, including E. coli and Enterobacter, in level IV NICU.. · All gram-negative isolates were meropenem-sensitive; vancomycin effective for gram-positives..

BackgroundPreterm birth, particularly very preterm birth (before 32 weeks of gestation), is a leading cause of neonatal morbidity and mortality. The early neonatal period is critical for preterm infants, with hematocrit levels serving as a important physiological indicator. We aimed to assess the relationship hematocrit in the first 2 hours of life and Short Outcomes in very preterm infants.MethodsThe research was a prospective cohort study completed by Dongli Song et al. We acquired data from the DATA DRYAD website and utilized exclusively for secondary analysis. From January 2008 to April 2014, data were gathered prospectively from eligible infants at the Santa Clara Valley Medical Center. The main outcomes included any Intraventricular Hemorrhage (IVH), any Retinopathy of Prematurity (ROP), Necrotizing Enterocolitis (NEC), chronic lung disease (CLD), and late-onset sepsis (LOS). Secondary outcomes were any intubation and any transfusion. We used multivariable logistic regression analyses to calculate adjusted odd ratio (OR) with 95% CI.ResultsThis study included 312 patients in total. Hematocrit in the first 2 hours of life, considered as a continuous variable, was significantly associated with short-term outcomes in univariate analyses (P < 0.05). After adjusting for GA, BW, and sex, only any ROP, any intubation, and any transfusion were statistically significant. With adjustments for multiple factors, the odds ratios for any ROP and any transfusion in infants whose Hematocrit was 45 or more in the first two hours of life, compared to those with an HCT less than 45 were 0.43 (95% CI, 0.19 ~ 0.97, p = 0.043) and 0.29 (95% CI, 0.12 ~ 0.7, p = 0.006).ConclusionsOur study shows that higher HCT in the first 2 hours of life was statistically significant association with decreased ROP and blood transfusion in very preterm infants. Further clinical trials are necessary to confirm and validate this association.

The aim of this study (PTX-trial) is to determine the optimal dose of pentoxifylline (PTX) in preterm neonates (gestational age < 30 weeks) with (suspected) late onset sepsis (LONS). The PTX-trial is a prospective multicentre open-label sequential dose-optimization study with an adapted continual reassessment method. An up-and-down dose-response design was used, with dose step-up and step-down titration per three patients with a PTX dose of 30 mg/kg/day in 6 h for 3 days in the first group. The primary outcome was an ED75, which was defined as a both clinical and chemical effective dose for 75% of preterm neonates with LONS. In total, 30 neonates were included in the study. As an effective dose was only observed in 27% of the patients, the ED75 could not be determined. There were no significant differences in biochemical and clinical response between the different dosage groups. The largest decrease in nSOFA score after start of PTX was observed in the dosage group of 30 mg/kg/day in 6 h. In this dose-finding trial for PTX in preterm neonates, our findings reveal no discernible clinical advantage associated with either increasing or decreasing the PTX dosage. The relatively high variability in sepsis severity and patients' post-natal ages increase the uncertainty of our findings, but the standardly used dosage of 30 mg/kg/day (5 mg/kg/h for 6 h) has consistently demonstrated safe tolerability without any reported severe adverse events.

Early phosphate supplementation reduces refeeding syndrome and improves clinical outcomes in very-preterm infants: A retrospective cohort study.

To evaluate the trends in mortality for early- and late-onset neonatal sepsis, as well as the attributable risk factors at global, regional and national levels from 1990 to 2021. Early-onset sepsis occurs within 0-6 days after birth, whereas, late-onset sepsis occurs between 7 and 27 days of life. Data on deaths from early- and late-onset neonatal sepsis, as well as the proportion attributable to risk factors, was sourced from the Global Burden of Disease Study (GBD) 2021. Temporal trends in mortality rates were assessed using estimated annual percentage changes. In 2021, global deaths from early- and late-onset neonatal sepsis totalled 136 040 and 70 411, respectively, corresponding to mortality rates of 5549.9 and 965.3 per 100 000 population. Both early- and late-onset neonatal sepsis mortality declined from 1990 to 2021, with a more pronounced reduction in late-onset sepsis. However, total deaths increased in low-SDI regions, driven by early-onset sepsis. The highest mortality rates were observed in Sub-Saharan Africa, particularly in Western and Eastern Sub-Saharan Africa. In 2021, short gestation (gestational age < 38 weeks) and low birth weight (< 2500 g) were responsible for 29.6% and 66.3% of neonatal sepsis deaths globally. Mortality rates showed an inverse correlation with SDI, with higher-SDI regions experiencing faster reductions in mortality. Neonatal sepsis remains a major global health challenge, particularly in low-SDI regions. Interventions targeting preterm birth, low birth weight and healthcare infrastructure are urgently needed.

Background/Objectives: The incidence of late-onset sepsis (LOS) has increased with improved survival rates in premature infants. Blood culture, the diagnostic "gold standard", requires at least 36-72 h for results, leading to empiric antibiotic use and potential resistance. MicroRNAs (miRNAs) have emerged as promising biomarkers for sepsis in adults, but their role in neonatal LOS remains unclear. The aim of this scoping review is to identify the miRNA expression profiles of bacterial LOS in neonates. Methods: A scoping review of the literature was performed between 1 November 2023 and 31 December 2024. Results: Twelve studies fulfilled our criteria and were included in the review. Despite the considerable heterogeneity among the studies, most focused on detecting and quantifying serum microRNAs using real-time PCR, while some examined correlations with other biomarkers, such as CRP. The few microRNAs identified as common across multiple studies showed similar patterns of regulation in LOS cases. Compared to controls (no LOS), neonates with LOS exhibited significant alterations in miRNA expression. More precisely, in LOS, miRNA-181a, miRNA-23b, miRNA-181b5p, miRNA-21-5p, miRNA-34a5p, miRNA-199a3p, miRNA-1184 and miRNA-1295p were downregulated, while miRNA-16, miRNA-146a, miRNA-101, miRNA-187, miRNA-21, miRNA-15a/16 and miRNA-455-5p were upregulated. Conclusions: Currently, there is limited data regarding miRNA expression in LOS. Many studies showed altered expression of specific miRNAs in septic neonates; however, these observations need further validation in larger cohorts and/or randomized controlled trials to confirm their diagnostic potential.

Recent studies suggest that early achievement of full enteral feeding improves clinical outcomes among preterm infants. To examine the association between full enteral feeding and late-onset sepsis. This secondary analysis of a cohort study prospectively followed up a multicenter cohort of preterm infants with gestational ages ranging from 23 to 28 weeks born between January 1, 2012, and December 31, 2021, at 19 US academic centers. Infants without major anomalies who received enteral feedings and survived beyond postnatal day 7 were included. Full enteral feeding (≥120 mL/kg/d). The primary outcome was the incidence of late-onset sepsis confirmed through culture-positive results occurring more than 72 hours after birth and treated with antibiotics for 5 or more days. Other clinical outcomes assessed up to 36 weeks of postmenstrual age included necrotizing enterocolitis, death, and growth faltering (weight, length, or head circumference z score decrease >1.2). Risk estimates were adjusted for clinical variables associated with acute critical illness and birth year. Demographic and clinical data from 15 102 preterm infants were analyzed (mean [SD] maternal age, 28.7 [6.1] years; mean [SD] gestational age, 26.0 [1.6] weeks; mean [SD] birth weight, 875 [242] g; 7648 male [50.6%]). Between January 1, 2012, and December 31, 2021, the median (IQR) time to achieve full enteral feeding decreased from 18 (14-28) days to 14 (10-22) days, and the incidence of late-onset sepsis decreased from 21.1% to 16.5% (P = .003). In adjusted analyses, the relative risk of late-onset sepsis per each additional 1-week delay in achieving full enteral feeding was 16% higher (adjusted relative risk [ARR], 1.16; 95% CI, 1.14-1.18; P < .001). Delays in achieving full enteral feeding were also associated with a higher risk of necrotizing enterocolitis (ARR, 1.20; 95% CI, 1.16-1.24; P < .001) and growth faltering in weight (ARR, 1.08; 95% CI, 1.07-1.09), length (ARR, 1.03; 95% CI, 1.02-1.03), and head circumference (ARR, 1.07; 95% CI, 1.06-1.08; P < .001 for all). In this cohort study of preterm infants with gestational ages ranging from 23 to 28 weeks who received enteral feeds and survived beyond postnatal day 7, delays in establishing full enteral feeding were associated with a higher risk of late-onset sepsis. These results suggest that early initiation and advancement of enteral feeding have the potential to reduce the risk of late-onset sepsis, growth faltering, and necrotizing enterocolitis.

ObjectiveTo investigate the risk factors associated with complications in infants with late-onset Group B Streptococcal (GBS) sepsis, and to provide evidence for clinical intervention strategies.MethodsThis study is a retrospective case-control study. The clinical data of 101 infants with late-onset GBS sepsis, diagnosed before 3 months of age were retrospectively analyzed. According to the presence or absence of complications, the infants were divided into the complication group and the non-complication group. Univariate and multivariate analyses were performed to explore the risk factors associated with the occurrence of complications in infants with late-onset GBS sepsis. Using ROC curves to evaluate the predictive efficacy of clinical variables.ResultsA total of 101 cases of late-onset GBS sepsis met the inclusion criteria, including 41 in the non-complication group and 60 in the complication group. The gestational age in the complication group was significantly lower than that in the non-complication group (P < 0.05). Clinically, the complication group had a higher incidence of seizure, bulging anterior fontanelle, and fever, as well as a significantly lower PaO2/FiO2 ratio (P < 0.05). Laboratory findings showed that the complication group had a higher incidence of hypoalbuminemia, concomitant positivity in blood and cerebrospinal fluid cultures, elevated creatinine and blood urea nitrogen levels, and significantly lower pH and albumin levels (P < 0.05). In addition, the complication group exhibited significantly higher Pediatric Sequential Organ Failure Assessment (pSOFA) scores, Pediatric Logistic Organ Dysfunction Score 2 (PELOD-2) scores, and higher proportion of patients with high pSOFA (>3.50) and PELOD-2 scores (>3.50) (P < 0.05). Multivariate analysis revealed that high PELOD-2 score, high pSOFA score, high creatinine levels and hypoalbuminemia were risk factors for the development of complications in infants with late-onset GBS sepsis; the ROC curve constructed using these predictors demonstrated excellent discriminative ability, with an AUC of 0.858 (95% CI: 0.782–0.934), sensitivity of 77.78%, and specificity of 82.61%.ConclusionHigh PELOD-2 score, high pSOFA score, high creatinine levels, and hypoalbuminemia independently predict complications in late-onset GBS sepsis infants, enabling early risk stratification and tailored treatment to improve outcomes.

This study determined factors associated with persistent bloodstream infections (BSIs) for infants in the NICU to identify when follow up blood cultures (FUBCs) have increased utility. Single center study of all infants in a level IV NICU (n = 121) with a positive blood culture over a five-year period. Clinical and microbiological variables were examined with bivariate and multi-regression analyses to identify factors associated with persistent BSI, defined as growth of the same organism >48 h after the index culture. The recovery of Staphylococcus aureus (OR = 6.10, p < 0.001), male sex (OR = 3.31, p = 0.020), the presence of a central venous catheter (OR = 3.73, p = 0.020), and BSI in the setting of late-onset sepsis (p < 0.001) were associated with persistent BSI. No infants with either early-onset sepsis or growth of Streptococcal sp. had a persistent BSI. In the NICU, both patient and microbial characteristics can inform diagnostic stewardship regarding the need for FUBCs.

BackgroundNeonatal chylothorax is associated with high morbidity and mortality, partly due to increased infection risk from lymphocyte depletion and hypogammaglobulinemia. However, data specific to chylothorax cohorts are limited. This study aimed to investigate lymphocyte subsets and immunoglobulin levels in neonates with congenital and acquired chylothorax.MethodsWe retrospectively enrolled 18 neonates with chylothorax admitted to our NICU between January 2023 and January 2025. Inclusion criteria were term or preterm infants with congenital or acquired chylothorax and paired peripheral blood and chyle samples collected within 48 hours of effusion onset. Lymphocyte subsets and immunoglobulin levels were compared between blood and chyle, and between congenital and acquired chylothorax.ResultsChyle samples showed significantly higher leukocyte, lymphocyte (percentage and absolute), and T-cell counts compared to blood. Conversely, B lymphocyte percentages and Natural killer (NK) cell counts were significantly lower in chyle, as were IgG and IgM levels. Three patients (16.7%) had absolute lymphopenia, particularly within the T-cell and NK-cell subsets, and five (27.8%) had hypogammaglobulinemia. Fifteen infants (83.3%) developed late-onset sepsis, primarily bacterial, with some fungal cases. Absolute T-cell subset numbers in chyle were higher in acquired versus congenital chylothorax, while percentages and immunoglobulin levels were largely similar.ConclusionOur findings confirm a specific pattern of immune dysregulation in neonates with chylothorax, with distinct lymphocyte and immunoglobulin profiles in chyle. In particular, the T-cell subsets were enriched in the chyle. A multicenter, prospective randomized trial is warranted to assess the utility of immunoglobulin therapy in infection prevention in this population.

Bacterial metabolite patterns of infants receiving multi-strain probiotics and risk of late-onset sepsis.

Compared to their healthy term peers, term infants with LOS experience greater challenges in sensory processing and motor development. These findings provide the first evidence that LOS in term-born infants is associated with early developmental impairments in sensory and motor domains. They should undergo comprehensive evaluations at key developmental stages to support optimal outcomes and be referred to intervention programs when needed. The study was registered with ClinicalTrials.gov with the number: NCT06884969-Registration Date: 03/13/2025. • Sepsis may contribute to white matter damage and widespread damage to premyelinating oligodendrocytes, increasing the likelihood of cognitive dysfunction later in life. • Premature infants are vulnerable to neonatal sepsis; however, it can also been seen in term newborns. • This is the first study to concurrently evaluate sensory processing and motor development at 12-18 months in term-born infants with culture-confirmed late-onset sepsis. • Term infants with late-onset sepsis show developmental delays in both sensory processing skills and motor development compared to their peers.

Introduction:Defined As The Systemic Condition That Arises From Viral, Bacterial Or Fungal Etiology, Associated With Hemodynamic Changes And Clinical Findings, Sepsis Is One Of The Most Common Causes Of Neonatal Mortality And Morbidity. Various Preventable Risk Factors Are Associated With The Developed Of Late-Onset Sepsis In Neonates. The Problem Of Neonatal Sepsis, Especially In Post-Op Neonates In Low-Income Countries Is Plagued By A Scarcity Of Research. Conducted In The Hdu Of Pediatric Surgery Department Of Holy Family Hospital, This Longitudinal Study Is Part Of The Quality Improvement Project To Improve Neonatal Outcomes. Objectives:This Study Aims To Identify The Risk Factors Associated With Late-Onset Sepsis In Post-Op Neonates In The Hdu Of Paeds Surgery Department Of Holy Family Hospital, A Tertiary Care Hospital In Punjab, Pakistan. In Addition To Risk Factors Already Elaborated By Previous Studies, This Study Also Aims To Delineate Additional Risk Factors Associated With Sepsis In The Context Of Post-Op Setups I.E. Fever Prior To Surgery, General Hygienic Measures Observed By The Attendants And Doctors And Severity Of Surgical Wounds. Methods:In Compliance With The Guidelines Issued By The Ethical Board, A Prospective Observational Study Recruiting 91 Neonates Was Carried Out For 6 Months From June, 2022 To December,2022. Periodic Evaluation Was Carried Out Using Standardized Checklists Which Recorded The Possible Predictor Variables I.E. Birth Weight, Severity Of Surgical Wounds, General Hygienic Practices, Fever Prior To Surgery And Duration Of Iv Catheterization. Data Obtained Was Subject To Multivariate Logistic Regression Using Spss V23. Results:Sepsis Was Prevalent In 34 (37.4%) Post-Op Neonates. Low Birth Weight [Or 3.08 95% Ci (1.12-8.47) And Fever Prior To Surgery [Or 2.79 95% Ci (1.03-7.55)] Were Found To Be Statistically Significant Factors Contributing To Neonatal Sepsis, Whereas The Study Of General Hygienic Practices, Severity Of Surgical Wounds And Duration Of Iv Catheterization Failed To Yield Statistically Significant Results, Possibly Owing To Small Sample Size. Conclusion:Further Studies Employing A Larger Sample Size Are Mandated In Order To Establish The Association Of The Aforementioned Risk Factors For Neonatal Sepsis. Low Birth Weight Neonates And Those With Fever Prior To Invasive Procedures Require Rigorous Monitoring For The Prompt Diagnosis And Prevention Of The Complications Associated With Neonatal Sepsis

Impact of the COVID-19 pandemic on morbidity and mortality in a Spanish cohort of very-preterm/very-low-birth weight newborns.

BackgroundPreterm infants have the highest incidence of late-onset sepsis, which could result in life-long morbidity, neurodevelopmental disability, and even death. We aimed to explore the anti-infection role of immune cells in treating preterm sepsis.MethodsThe single-cell RNA-seq (scRNA-seq) data of preterm newborns with late-onset sepsis were collected from the Gene Expression Omnibus database. The Seurat and harmony R package were used to perform the scRNA-seq analysis. Gene set enrichment analysis (GSEA) was conducted using the GSVA R package. FindAllMarkers and DAVID databases were used for differentially expressed genes (DEGs) analysis and function annotation of the genes, respectively. Transcriptional regulons analysis was performed applying the SCENIC tool.ResultsWe identified 8 cell clusters, among which the immune cells including the neutrophils, T helper, and NK cells distributed more in the sepsis samples. The immune activity of neutrophils was inhibited with less anti-inflammatory pathway activation. T cells and NK cells exhibited greater activation of immune and detoxification pathways, such as antimicrobial humoral immune response and cellular oxidant detoxification, which contributed to anti-infection response. GZMA + Cytotoxic T cells 2, GRASP + T cells, TMEM107 + NK cells, and GPR171 NK cells have a potential impact on promoting the immune response in preterm infant sepsis, and their key regulons including CREM, EST1, HSPA5, and STAT1 may be potential molecular targets for improving the sepsis treatment.ConclusionThe scRNA-seq analysis of preterm infants with late-onset sepsis revealed enrichment of T and NK cell subsets with heightened regulon activity and antibacterial/oxidative stress programs, indicating potential association with the host infection response.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40001-025-03272-1.

BackgroundResearch on the association of serum phosphate levels with the severity and prognosis of neonatal diseases is limited. Neonatal sepsis is the primary cause of neonatal mortality. Therefore, in this study, we aimed to investigate the association between serum phosphate levels and neonatal sepsis outcomes.MethodsThis retrospective cohort study was conducted using the Pediatric Intensive Care (PIC) database (2010–2018). Neonatal sepsis was diagnosed based on ICD-10 codes. Serum phosphate levels within 72 h of sepsis diagnosis were selected. Outcomes were severe sepsis, in-hospital mortality, length of hospital stay (hospital Los.), and ICU stay (ICU Los.). Covariates included demographic and clinical characteristics as well as serum biomarkers. Multi-variable regression and subgroup analyses were performed to explore the association between serum phosphate levels and neonatal sepsis outcomes.ResultsA total of 120 infants with neonatal sepsis were included, and their characteristics were analyzed according to serum phosphate tertiles. The median age was 3.0 (1.0, 17.0) days. The proportion of male infants was 62.5% (75/120). The proportion of preterm infants was 44.2% (53/120). The incidence of late-onset sepsis was 60.8% (73/120). Multivariate linear regression analysis showed that the serum phosphate level at sepsis diagnosis was associated with hospital Los. and remained so after adjustment for all covariates. Each 1 mmol/L decrease in serum phosphate level prolonged the length of hospital stay by 7.53 days. The low serum phosphate group had an 11.75-day longer hospital stay than the high serum phosphate group. Curve fitting showed a negative linear correlation between serum phosphate levels and hospital Los. in infants with neonatal sepsis and no significant interactions were observed in the subgroup analysis; however, serum phosphate levels were not independently associated with ICU Los. In addition, no correlation was found between serum phosphate levels and mortality or the severity of sepsis in neonates.ConclusionsHypophosphatemia is highly prevalent in neonates with sepsis. Lower serum phosphate levels are associated with prolonged hospital stay in neonates with sepsis. Strengthening the monitoring of serum phosphate levels in neonates with sepsis and maintaining the homeostasis of phosphate in the body can promote refined management of neonatal sepsis and help improve the prognosis of the patients.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12887-025-06209-z.

ObjectivesTo survey the current antibiotic and antifungal drug practices of UK neonatal intensive care units (NICUs), and to identify antibiotic preferences and policies for treatment of early- and late-onset sepsis (EoS and LoS), meningitis, and antifungal prophylaxis.MethodsBetween January and May 2024, we contacted all 53 tertiary-level UK NICUs via telephone and/or e-mail. We requested a copy of each unit’s guidelines for antibiotic treatment of EoS and LoS, and antifungal prophylaxis.ResultsWe obtained guidelines from 53/53 (100%) units. A penicillin and aminoglycoside combination was the consistent first-line recommendation for EoS in 51/53 (96%) units. Only a minority (11/53; 21%) units specified any second-line antibiotic regimen for EoS, though most (44/53; 83%) specifically recommended amoxicillin for suspected listeriosis. For LoS, almost all NICUs (52/53; 98%) provided specific guidance on empirical first-line antibiotic treatment, with empirical narrow-spectrum antibiotics as first-line LoS treatment for term neonates in 42/53 (79%) NICUs and for preterm neonates in 41/53 (77%) NICUs. Fifty-four percent (29/53) of units included specific LoS recommendations for neonates with indwelling central venous catheters. Sixty-six percent (35/53) of NICUs included cefotaxime in their empirical meningitis regimens. Eighty-five percent (45/53) of units had clear guidelines for antifungal prophylaxis.ConclusionsWhile EoS treatment was consistent across units, there remained wide variation in antibiotic regimens used for LoS and meningitis, and for neonates with indwelling central venous catheters. Guidelines specific to preterm neonates were limited. The practice of routine antifungal prophylaxis has been more prevalent since the last UK survey in 2006–07 but is still neither universal nor consistent.

IntroductionCompare outcomes of very preterm infants (VPIs) with a birth weight<1,500 g based on delivery mode and propensity score matching (PSM).MethodsThis was a retrospective study (2016–2021) of 1,375 VPIs (692 vaginal and 683 cesarean deliveries). PSM created 390 matched pairs. Outcomes included respiratory and neurological morbidity and mortality.ResultsPSM revealed no significant difference between the two groups at baseline or after antenatal corticosteroids administration. The incidence rates of birth asphyxia, delivery room resuscitation, neonatal respiratory distress syndrome, use of pulmonary surfactants, pulmonary hemorrhage, and use of invasive ventilation in the vaginal delivery group after PSM were 42.3, 68.2, 65.9, 59.2, 7.2, and 36.7%, respectively. These rates were significantly lower than those in the cesarean delivery group (52.3, 83.3, 79.5, 70.8, 14.4, and 51.8%, respectively) (p < 0.05). The difference was more significant in infants with a gestational age of 28–31+6 weeks (p < 0.05). There were no significant differences in the incidence rates of intraventricular hemorrhage (IVH), severe IVH, periventricular leukomalacia, bronchopulmonary dysplasia, necrotizing enterocolitis (NEC), NEC surgery, premature infant retinopathy (ROP), severe ROP, late-onset neonatal sepsis, or mortality between the two groups. The mortality rate within 3 days in the vaginal delivery group was 7.7%, which was higher than that in the cesarean delivery group (3.3%), primarily in infants with a gestational age < 28 weeks (p < 0.05).ConclusionCesarean section reduced early mortality in VPIs <28 weeks but increased respiratory morbidity at 28–31+6 weeks, with no impact on other outcomes. Since 52.1% of the cesarean sections were emergency procedures, this may have biased the results.

The skin-to-blood route is traditionally considered the main pathway in Candida late-onset sepsis (LOS) development in preterm infants. However, emerging evidence suggests that the gut also serves as a source of infection. We aimed to characterize fecal mycobiota and microbiota profiles preceding onset of Candida LOS to assess the role of the preterm gut microbiome in disease development. In this multicenter, case-control study, very preterm infants (<30 weeks of gestation) with Candida LOS were included. Each case was matched to non-affected controls by gestational and postnatal age, hospital site, and/or cumulative antibiotic exposure prior to day of LOS onset (t=0). Fecal samples collected at t=0 and the five preceding days were analyzed using ITS1 and 16S RNA sequencing. Microbial amplicon yields, composition, and inter-kingdom correlations were assessed. Of 2,397 screened infants, fecal samples were available for 8/19 infants with Candida LOS. In these 8 cases, the ITS/16S amplicon yield ratio was increased (p<0.001) and the relative abundance of fecal Candida albicans correlated positively with fungal amplicon yield (ρ=0.71, padj=0.005), suggesting increased absolute abundance up to five days before onset. Additionally, bacterial yields were significantly lower (p=0.02) and α-diversity was significantly decreased (p=0.012), compared to the controls. Increased fecal C. albicans preceded Candida LOS onset, implicating the preterm gut as a potential source of infection. Reduced bacterial yields and diversity suggest ecological alterations that may facilitate Candida pathogenicity in the preterm gut. These findings support further research into gut-derived Candida LOS and potential for microbiota-targeted prevention strategies.