| Differential roles of IL-6 and adrenomedullin in early diagnosis and mortality predictions in late-onset neonatal sepsis |
Emilly Henrique dos Santos1,2 
, Gabriel Acca Barreira1,2,3
, Mariana Okay Saippa1,4
, Maria Carolina Pires Cruz1,2
, Karen Alessandra Rodrigues1,2
, Ronaldo Arkader1
, Thelma Suely Okay1,2
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1Laboratório de Soroepidemiologia, Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
2Departamento de Pediatria, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
3Faculdade Israelita de Ciências da Saúde Albert Einstein, São Paulo, Brazil
4Faculdade de Medicina do ABC, Santo André, Brazil |
Correspondence:
Emilly Henrique dos Santos, Email: emilly.santos@usp.br
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Received: 14 October 2024 • Revised: 26 November 2024 • Accepted: 26 November 2024 |
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| Abstract |
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.
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| Key Words:
Interleukin 6, Adrenomedullin, C-Reactive Protein, Late Neonatal Sepsis, Diagnosis Biomarkers, Prognosis Biomarkers. |
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