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

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.