Neonatal leucocyte cell population data: reference intervals and relevance for detecting sepsis and necrotizing enterocolitis

Affiliations

¹ Clinic of Neonatology, Department Mother-Woman-Child, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. flavia.ferraro@hug.ch.
² Clinic of Neonatology, Department Mother-Woman-Child, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
³ Service of Hematology and Central Hematology Laboratory, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁴ Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁵ Clinical Data Science, Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁶ Swiss Data Science Center, Swiss Institute of Technology, Lausanne, Switzerland.
⁷ Clinic of Neonatology, Department Mother-Woman-Child, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. eric.giannoni@chuv.ch.

^# Contributed equally.

PMID: 40481289
DOI: 10.1038/s41390-025-04159-x

Neonatal leucocyte cell population data: reference intervals and relevance for detecting sepsis and necrotizing enterocolitis

Flavia Ferraro et al. Pediatr Res. 2025.

. 2025 Jun 6.

doi: 10.1038/s41390-025-04159-x. Online ahead of print.

Authors

Affiliations

¹ Clinic of Neonatology, Department Mother-Woman-Child, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. flavia.ferraro@hug.ch.
² Clinic of Neonatology, Department Mother-Woman-Child, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
³ Service of Hematology and Central Hematology Laboratory, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁴ Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁵ Clinical Data Science, Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁶ Swiss Data Science Center, Swiss Institute of Technology, Lausanne, Switzerland.
⁷ Clinic of Neonatology, Department Mother-Woman-Child, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. eric.giannoni@chuv.ch.

^# Contributed equally.

PMID: 40481289
DOI: 10.1038/s41390-025-04159-x

Abstract

Background: Timely diagnosis of neonatal sepsis is crucial but remains challenging. Cell Population Data (CPD) provide high-resolution phenotyping of leukocytes, offering potential for sepsis detection. We aimed to establish neonatal CPD reference intervals and explore their capacity to detect sepsis and necrotizing enterocolitis (NEC).

Methods: CPD from neutrophils, monocytes, and lymphocytes were analyzed in hospitalized newborns. Reference intervals (5-95th percentiles), at birth and during the first 28 days, were derived from newborns without conditions potentially impacting CPD (reference group). The performance of CPD in detecting blood culture-proven sepsis/NEC was evaluated against complete blood count (CBC) and C-reactive protein (CRP).

Results: Reference intervals from 905 neonates showed that mean CPD values followed distinct trajectories for each parameter, while distribution width generally decreased with increasing gestational and postnatal age. CPD in 39 sepsis/NEC cases, obtained on the day of clinical suspicion or from the closest CBC, differed from those in the reference group, particularly neutrophil fluorescence intensity (NE-SFL) (56.2 vs. 41.1 arbitrary units, P < 0.001). NE-SFL had superior accuracy compared to other CPD, CBC, and CRP, with 90% sensitivity and 76% specificity.

Conclusions: This study establishes neonatal CPD reference intervals and identifies NE-SFL as a potential sepsis biomarker.

Impact: This study establishes reference intervals for neonatal leukocyte Cell Population Data (CPD), providing a valuable resource for interpreting these preclinical parameters in newborns. Our findings highlight the impact of gestational and postnatal age on neutrophil, monocyte, and lymphocyte morphology, contributing to a better understanding of neonatal immune development. In an exploratory analysis, CPD parameters, particularly NE-SFL, had superior diagnostic accuracy for sepsis and necrotizing enterocolitis compared to traditional biomarkers. As CPD are automatically generated with CBC, they offer a cost-effective, real-time, and objective tool with potential for improving neonatal sepsis detection.

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Consent for publication: The need for informed consent was waived, as the potential difficulties in obtaining consent were considered disproportionate to the low risk and observational nature of the study. Caregiver acceptance or non-refusal of the general consent for research was required for inclusion in this study. Only those who explicitly refused consent were excluded.

References

1. Strunk, T., Molloy, E. J., Mishra, A. & Bhutta, Z. A. Neonatal bacterial sepsis. Lancet 404, 277–293 (2024). - PubMed - DOI
1. Fleischmann-Struzek, C. et al. The global burden of paediatric and neonatal sepsis: a systematic review. Lancet Respir. Med. 6, 223–230 (2018). - PubMed - DOI
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1. Giannoni, E. et al. Analysis of antibiotic exposure and early-onset neonatal sepsis in Europe, North America, and Australia. JAMA Netw. Open 5, e2243691 (2022). - PubMed - PMC - DOI

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Neonatal leucocyte cell population data: reference intervals and relevance for detecting sepsis and necrotizing enterocolitis

Affiliations

Neonatal leucocyte cell population data: reference intervals and relevance for detecting sepsis and necrotizing enterocolitis

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous