Background: The epidemiology of early-onset sepsis (EOS) in China is poorly understood because of the paucity of high-quality data. We aimed to examine the epidemiology, pathogen distribution and neonatal outcomes of EOS among a large cohort of preterm infants in China. Methods: All infants born at <34 weeks of gestation and admitted to 25 tertiary neonatal intensive care units in China from April 2015 to May 2018 were enrolled. EOS was defined as a culture-confirmed infection that occurred within 72 hours after birth. Results: Among 27,532 enrolled infants, 321 (11.7 cases per 1000 admissions) infants developed EOS, and 61 (19.0%) infants died within seven days after EOS onset. The incidence of EOS among inborn infants in 18 perinatal centers was 9.7 cases per 1000 live births <34 weeks’ gestation (186/19,084). The case fatality rate was 22.6% (42/186). Gram-negative bacteria were responsible for 61.7% of EOS and 82.0% of EOS-related deaths. Escherichia coli (20.3%) was the leading pathogen, followed by Coagulase-negative staphylococcus (16.5%), Achromobacter xylosoxidans (9.0%) and Klebsiella pneumoniae (8.1%). Group B streptococci infections were relatively rare (2.5%). EOS was an independent risk factor for all-cause mortality and retinopathy of prematurity. Conclusions: There is a high burden of EOS among preterm infants in China with a distinctive pathogen distribution. Longitudinal epidemiologic monitoring, further investigation of causative pathogens and development of targeted strategies for prevention and treatment of EOS are needed.

OBJECTIVES: To determine whether use, duration, and types of early antibiotics were associated with neonatal outcomes and late antibiotic use in preterm infants without infection-related diseases. METHODS: This cohort study enrolled infants admitted to 25 tertiary NICUs in China within 24 hours of birth during 2015–2018. Death, discharge, or infection-related morbidities within 7 days of birth; major congenital anomalies; and error data on antibiotic use were excluded. The composite outcome was death or adverse morbidities. Late antibiotic use indicated antibiotics used after 7 days of age. Late antibiotic use rate was total antibiotic use days divided by the days of hospital stay after the first 7 days of life. RESULTS: Among 21 540 infants, 18 302 (85.0%) received early antibiotics. Early antibiotics was related to increased bronchopulmonary dysplasia (BPD) (adjusted odds ratio [aOR], 1.28; 95% confidence interval [CI], 1.05-1.56), late antibiotic use (aOR, 4.64; 95% CI, 4.19-5.14), and late antibiotic use rate (adjusted mean difference, 130 days/1000 patient-days; 95% CI, 112-147). Each additional day of early antibiotics was associated with increased BPD (aOR, 1.07; 95% CI, 1.04-1.10) and late antibiotic use (aOR, 1.41; 95% CI, 1.39-1.43). Broad-spectrum antibiotics showed larger effect size on neonatal outcomes than narrow-spectrum antibiotics. The correlation between early antibiotics and outcomes was significant among noncritical infants but disappeared for critical infants. CONCLUSIONS: Among infants without infection, early antibiotic use was associated with increased risk of BPD and late antibiotic use. Judicious early antibiotic use, especially avoiding prolonged duration and broad-spectrum antibiotics among noncritical infants, may improve neonatal outcomes and overall antibiotic use in NICUs.

Scope: Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in preterm infants, occurring more often in formula-fed infants than in breastfed infants. Recent animal studies have shown that cells in fresh breast milk survive in the newborns' digestive tract. However, no clinical studies have been conducted on the effects of human milk cells, and their biological roles in the infants' intestines remain unexplored. Methods and Results: Twenty premature infants are enrolled. Cells from fresh milk of their own mothers are enriched and fed to infants with Bell's Stage I NEC once a day for 7 days since the onset of NEC. Fecal samples are collected at enrollment and 2 weeks later. Fecal sphingolipids are observed to be enriched in NEC patients and positively correlated with calprotectin levels. After intervention with enriched human milk cells, inflammation-associated sphingolipids and microbiome profiles are altered and resembled those of the controls. Conclusion: These preliminary findings reveal the potential impacts of enriched human milk cells on premature infants with Bell's Stage I NEC and provide insight into the roles of fecal sphingolipid metabolism in the neonates' intestinal inflammation. However, the limited sample size of the study indicates the need for further investigation.

INTRODUCTION: To elucidate the postnatal dynamics and clinical associations of fecal calprotectin (FC) in very preterm infants, with a focus on necrotizing enterocolitis (NEC) and feeding intolerance (FI). METHODS: We performed a prospective observational cohort study in infants with a gestational age of <32 weeks or birth weight <1,500 g with weekly feces collection. The relationships between FC, NEC, and FI were investigated, adjusting for demographic and clinical factors. RESULTS: A total of 1,086 fecal samples were collected from 194 preterm infants. Postnatal FC levels of non-NEC infants were highly variable and followed an age-dependent patterned progression. FC levels were elevated in patients with NEC before and at NEC onset, distinguishing them from non-NEC infants and those at sepsis onset. Among infants without NEC or sepsis, those with FI exhibited lower FC concentrations throughout hospitalization and displayed a significant delay in reaching high FC levels after meconium compared with non-FI infants. The age to reach the first high nonmeconial FC levels was positively associated with the time to achieve full enteral feeding. DISCUSSION: Postnatal FC dynamics among premature infants followed a patterned progression but were disturbed in patients with NEC and FI. Because of the high variations, the use of FC levels in NEC diagnosis should be implemented with caution in clinical practice. FC may help understand FI and feeding progression in very preterm infants. Further research is needed to validate these findings and explore the potential clinical applications of FC in this population.