Objectives: To describe the rates and variability of mortality and morbidity of preterm infants born in China. Methods: This prospective cohort study included infants born at <34 weeks' gestation and admitted to 25 NICUs within 7 days of birth between May 1st, 2015 and April 30th, 2016. Infants were followed until death or NICU discharge. The primary outcome was a composite of mortality or any major morbidity (sepsis, necrotizing enterocolitis, intraventricular/periventricular leukomalacia, retinopathy of prematurity, and bronchopulmonary dysplasia) in infants who received complete care following medical advice. Secondary outcomes included rate of discharge against medical advice, mortality and individual morbidities. Results: Of the 8,065 infants, 6,852 (85%) received complete care and 1,213 (15%) were discharged against medical advice. Among infants who received complete care, the rate of the composite outcome was 27% (1,827/6,852), mortality 4% (248/6,852), sepsis 14% (990/6,852), necrotizing enterocolitis 3% (191/6,550), intraventricular hemorrhage/periventricular leukomalacia 7% (422/6,307), retinopathy of prematurity 2% (67/3,349), and bronchopulmonary dysplasia 9% (616/6,852). There were significant variations between NICUs for all outcomes. Conclusions: Discharged against medical advice, mortality, and morbidity rates for preterm infants <34 weeks' gestation are high in China with significant variations between NICUs.

To describe the incidence, case-fatality rate and pathogen distribution of late-onset sepsis (LOS) among preterm infants in China and to investigate risk factors and short-term outcomes associated with LOS caused by Gram-positive bacteria, Gram-negative bacteria and fungi. This cohort study included all infants born at <34 weeks' gestation and admitted to 25 tertiary hospitals from 19 provinces in China from May, 2015 to April, 2018, excluding infants who died or were discharged within 3 days of life. Totally 1199 episodes of culture-positive LOS were identified in 1133 infants, with an incidence of 4.4% (1133/25725). Overall, 15.4% (175/1133) of infants with LOS died and 10.0% (113/1133) of infants died within 7 days after LOS onset. Among 1214 pathogens isolated, Gram-negative bacteria were the most common pathogens (51.8%, 629/1214). Fungi accounted for 17.1% (207/1214) of pathogens. Use of central lines, longer duration of antibiotics and previous carbapenem exposure were related with increased risk of fungal LOS compared with Gram-positive bacteria. Gram-negative bacteria LOS was independently associated with increased risk of death, periventricular leukomalacia, bronchopulmonary dysplasia and necrotizing enterocolitis. Fungal LOS was independently associated with increased risk of periventricular leukomalacia, bronchopulmonary dysplasia and necrotizing enterocolitis. LOS was a significant cause of morbidity and mortality in Chinese NICUs with a distinct pathogen distribution from industrial countries. Clinical guidelines on the prevention and treatment of LOS should be developed and tailored to these LOS characteristics in Chinese NICUs.

Background: Culture-negative late-onset sepsis (LOS) is commonly diagnosed in neonatal intensive care units, while the outcomes of neonatal culture-negative LOS are not reported for large cohorts. This study aimed to examine the incidence and neonatal outcomes for culture-negative LOS in a contemporary multicenter cohort of preterm infants. Methods: We performed a retrospective analysis of data from a cluster-randomized controlled study. Infants <34 weeks of gestation and admitted to 25 neonatal intensive care units between May 1, 2015, and April 30, 2018, were included. Culture-negative LOS was diagnosed if infants had abnormal manifestations and laboratory tests but negative blood cultures. The primary outcome was a composite of mortality or morbidities including periventricular leukomalacia (PVL), retinopathy of prematurity (ROP) ≥ stage 3 or bronchopulmonary dysplasia (BPD). Results: Of 22,346 eligible infants, 1505 (6.7%) infants had culture-negative and 761 (3.4%) infants had culture-positive LOS. Compared with infants without LOS, infants with culture-negative LOS had higher rates of composite outcome (24.1% vs. 9.6%), death (3.8% vs. 1.8%), PVL (4.8% vs. 2.2%), severe ROP (3.3% vs. 1.1%) and BPD (18.1% vs. 7.0%). After adjustment, culture-negative LOS was independently associated with increased risk of composite outcome {adjusted odds ratio [aOR]: 1.8 [95% confidence interval (CI): 1.5–2.1]}, PVL [aOR: 2.0 (95% CI: 1.4–2.8)] and BPD [aOR: 1.8 (95% CI: 1.5–2.2)] relative to the absence of LOS. Conclusion: Culture-negative LOS was frequently diagnosed in preterm infants and was associated with increased risks of adverse outcomes. There is an emerging need for more precise diagnosis and treatment strategies for culture-negative LOS.

Early-onset sepsis (EOS) poses a substantial risk to very preterm infants, necessitating the prevalent administration of empirical antibiotics in the neonatal intensive care unit (NICU). Puopolo et al¹ reported that more than one-third of the extremely preterm infants in their study were categorized as low risk for EOS, with an incidence of 0.5%. In these low-risk groups, prolonged empirical antibiotic treatment (≥5 days) was observed in approximately 35% of cases.¹ Recent studies^1-3 have suggested a potential association of prolonged antibiotic therapy with both increased mortality and a higher incidence of adverse neonatal outcomes, including bronchopulmonary dysplasia (BPD), within this vulnerable population. However, these studies often relegated BPD as a secondary outcome, lacking comprehensive consideration of relevant confounding factors. Moreover, the literature has reported inconsistent results in this domain.^4-6 The reported association may be influenced by factors such as culture-proven sepsis bacteremia, illness severity, and early respiratory disease.