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

Timely diagnosis of neonatal sepsis is crucial but remains challenging with existing tools. Cell Population Data (CPD) provide high-resolution phenotypic analysis of leukocytes, offering potential for sepsis detection. We aimed to establish neonatal CPD reference intervals and explore their potential for early recognition of sepsis and necrotizing enterocolitis (NEC). Neutrophil, monocyte, and lymphocyte CPD from hospitalized newborns were analyzed. Reference intervals (5th to 95th percentiles), at birth and during the first 28 days, were derived from newborns without conditions potentially impacting CPD (controls). CPD obtained on the day of clinical suspicion from newborns with blood culture-proven sepsis and/or NEC were compared to controls, and their performance in detecting sepsis/NEC was compared with complete blood count (CBC) and C-reactive protein (CRP). Reference intervals from 905 controls showed that mean CPD values had distinct trajectories for each parameter, while distribution width generally decreased with increasing gestational and postnatal age. CPD in 39 sepsis/NEC cases differed from controls, particularly neutrophil fluorescence intensity (NE-SFL) (56.2 vs. 41.1 arbitrary units, P < 0.001). NE-SFL had superior accuracy over other CPD, CBC, and CRP, with 90% sensitivity and 76% specificity. This study establishes neonatal CPD reference intervals and identifies NE-SFL as a potential sepsis biomarker.