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Updated: May 27, 2025
A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
Biomarker Potential of Interleukin-6 in Differentiating Necrotizing Enterocolitis from Late-Onset Sepsis in Neonates
Ceren Imren1, Vivian de Groot2, Claudia M G Keyzer-Dekker1
1Department of Pediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands.
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, P < .001) for every doubling of IL-measurements. IL-6 was not associated with the odds of surgical NEC compared with medical NEC. IL-6's ability to distinguish NEC from LOS was moderate (AUC 0.73). IL-6 combined with C-reactive protein (AUC 0.64) showed poor discriminative ability.
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.
