Differential roles of IL-6 and adrenomedullin in early diagnosis and mortality predictions in late-onset neonatal sepsis

Background: Diagnosing and predicting neonatal sepsis is challenging because of its nonspecific symptoms, lack of diagnostic criteria consensus, and absence of early, sensitive, and specific diagnostic laboratory tests.

Purpose: To evaluate the diagnostic and prognostic potential of adrenomedullin (ADM), interleukin-6 (IL-6), and C-reactive protein (CRP) in late-onset neonatal sepsis (LOS).

Methods: We studied 53 neonates with culture-proven LOS by sampling at admission and on antibiotic treatment days 3 and 7. These data were compared with those of 22 healthy full-term controls sampled on day 3 before hospital discharge. Survivors and non-survivors in the sepsis group were analyzed separately.

Results: Coagulase-negative Staphylococcus was the most commonly detected pathogen. ADM (cutoff, 0.5 ng/mL) and CRP (cutoff, <5 mg/L) values aligned with manufacturer recommendations, while IL-6 levels (cutoff, 10 pg/mL) were higher than expected, likely due to labor stress. The median biomarker levels significantly distinguished neonates with sepsis from controls (p < 0.0001) at all time points with ADM and IL-6 levels elevated at admission, indicating their potential as early diagnostic markers. CRP level was diagnostically useful starting on day 3. Prognostically, IL-6 (p < 0.001) and ADM (p < 0.05) differentiated survivors from non-survivors; however, only IL-6 consistently predicted mortality at all time points (area under the curve [AUC] > 0.90). ADM and CRP levels showed poor prognostic value (AUC < 0.70). ADM and IL-6 demonstrated strong diagnostic utility in early LOS, whereas CRP became relevant later. IL-6 was the only reliable biomarker for predicting mortality, supporting its integration into clinical protocols. Combining IL-6 with CRP may enhance early detection and management, potentially improving neonatal outcomes.

Conclusion: IL-6 is a robust biomarker for the early diagnosis and prognosis of LOS. Incorporating IL-6 into clinical practice with CRP could improve early neonatal LOS diagnosis and patient outcomes.