Biomarker Potential of Interleukin-6 in Differentiating Necrotizing Enterocolitis from Late-Onset Sepsis in Neonates Born Preterm.

Objective: Interleukin-6 (IL-6) is an early biomarker for sepsis and necrotizing enterocolitis (NEC). We assessed IL-6's ability to differentiate between late-onset sepsis (LOS) and NEC and between medical and surgical NEC. Study design: This retrospective cohort study included infants born preterm (birth weight <1500 g, gestational age <32 weeks) with ≥1 episodes of suspected late-onset sepsis (sLOS) between 2018 and 2023. Plasma IL-6 levels at sLOS onset were analyzed. Infants were grouped into (1) control (no sepsis/NEC), (2) LOS (culture negative/positive sepsis), or (3) NEC (medical/surgical), on the basis of the greatest classification of their observed episodes. IL-6's predictive value (alone and in combination with C-reactive protein) for sLOS outcomes was assessed with receiver operating characteristic analysis, with the area under the curve (AUC) quantifying its discriminative quality. Results: sLOS was observed in 421 infants (670 episodes); 131 (31%) had no LOS or NEC, 225 (53%) had LOS without NEC, and 65 (15%) had NEC. Median IL-6 values significantly differed between all groups, with highest in infants with NEC. The odds of NEC over LOS increased by a factor of 1.53 (95% CI 1.42-1.65, Conclusions: Although elevated IL-6 levels are associated with greater odds of having NEC instead of LOS, the moderate predictive value suggests that IL-6 alone may not be sufficient for accurate early diagnosis or differentiation.