Late-Onset Sepsis among Extremely Preterm Infants of 24-28 Weeks Gestation: An International Comparison in 10 High-Income Countries

Neonatology. 2024;121(6):761-771. doi: 10.1159/000539245. Epub 2024 Jun 18.

Abstract

Introduction: Despite advances in neonatal care, late-onset sepsis remains an important cause of preventable morbidity and mortality. Neonatal late-onset sepsis rates have decreased in some countries, while in others they have not. Our objective was to compare trends in late-onset sepsis rates in 9 population-based networks from 10 countries and to assess the associated mortality within 7 days of late-onset sepsis.

Methods: We performed a retrospective population-based cohort study. Infants born at 24-28 weeks' gestation between 2007 and 2019 were eligible for inclusion. Late-onset sepsis was defined as a positive blood or cerebrospinal fluid culture. Late-onset sepsis rates were calculated for 3 epochs (2007-11, 2012-15, and 2016-19). Adjusted risk ratios (aRRs) for late-onset sepsis were calculated for each network.

Results: Of a total of 82,850 infants, 16,914 (20.4%) had late-onset sepsis, with Japan having the lowest rate (7.1%) and Spain the highest (44.6%). Late-onset sepsis rates decreased in most networks and remained unchanged in a few. Israel, Sweden, and Finland showed the largest decrease in late-onset sepsis rates. The aRRs for late-onset sepsis showed wide variations between networks. The rate of mortality temporally related to late-onset sepsis was 10.9%. The adjusted mean length of stay for infants with late-onset sepsis was increased by 5-18 days compared to infants with no late-onset sepsis.

Conclusions: One in 5 neonates of 24-28 weeks' gestation develops late-onset sepsis. Wide variability in late-onset sepsis rates exists between networks with most networks exhibiting improvement. Late-onset sepsis was associated with increased mortality and length of stay.

Keywords: Extremely preterm infants; Late-onset sepsis; Mortality; Trends.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Developed Countries*
  • Female
  • Gestational Age*
  • Humans
  • Infant
  • Infant Mortality / trends
  • Infant, Extremely Premature*
  • Infant, Newborn
  • Male
  • Neonatal Sepsis* / epidemiology
  • Neonatal Sepsis* / mortality
  • Retrospective Studies
  • Sepsis / epidemiology
  • Sepsis / mortality

Grants and funding

The International Network for Evaluating Outcomes of Neonates (iNeo) has been supported by the Canadian Institutes of Health Research [APR-126340 and PBN 150642 to P.S.S.]. The Australian and New Zealand Neonatal Network is predominantly funded by membership contributions from the participating centers. The Canadian Neonatal Network is supported by a team grant from the Canadian Institutes of Health Research [CTP 87518] and by the participating centers. The Finnish Medical Birth Register is governmentally funded and kept by the National Institute for Health and Welfare (THL). The Israel Neonatal Network very low birth weight infant database is partially funded by the Israel Center for Disease Control and the Ministry of Health. The Neonatal Research Network of Japan is partly funded by a Health Labour Sciences Research Grant from the Ministry of Health, Labour, and Welfare of Japan. The Spanish Neonatal Network is supported by funds from the Spanish Neonatal Society (SENeo). The Swedish Neonatal Quality Register is funded by the Swedish Government (Ministry of Health and Social Affairs), the Swedish Association of Local Communities and Regions (SALAR), and the participating units. The Swiss Neonatal Network is partially funded by the participating units in the form of membership fees. This research was also supported by Instituto de Investigación Sanitaria Carlos III (Ministry of Science, Innovation and Universities, Kingdom of Spain) (FIS17/0131 to M.V.) and RETICS, funded by the PN 2018–2021 (Spain), ISCIII-Sub-Directorate General for Research Assessment and Promotion, and the European Regional Development Fund (ERDF) [RD16/0022] and by grants from a regional agreement on clinical research (ALF) between Region Stockholm and Karolinska Institutet [2020-0443 to M.N.]. The funding body played no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.