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Selected Publication:
Eichberger, J.
IL-6 as diagnostic marker for neonatal sepsis – alone and in combination with other inflammatory markers
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2023. pp. 58
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- Authors Med Uni Graz:
- Advisor:
- Resch Bernhard
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- Abstract:
- Background: Neonatal sepsis is a major cause of morbidity and mortality in both preterm and term infants. Early onset neonatal sepsis (EONS) presents within the first 72h of life, while late onset sepsis (LOS) occurs after this time. Diagnosis is difficult as signs and symptoms are nonspecific, and routinely used laboratory tests can neither confirm nor rule out neonatal sepsis. Inflammatory markers are widely used as an additional diagnostic tool. Interleukin-6 (IL-6) is part of the fetal inflammatory response syndrome (FIRS) and therefore an interesting early marker for neonatal sepsis. Methods: IL-6 diagnostic accuracy studies for diagnosing neonatal sepsis published between 1990 and 2020 were retrieved using the PubMed database and systematically reviewed. IL-6 was analysed as a sole marker and in combination with other inflammatory markers for the diagnosis of early onset sepsis. The diagnostic potential of IL-6 was correlated with gestational age, timing and site of sample collection. Sensitivity and specificity values and positive and negative predictive values of IL-6 were reported and subgroup analyses performed. The quality of IL-6 diagnostic accuracy studies was assessed using a STARD checklist adapted for neonates with neonatal sepsis. Results: We identified 31 studies on IL-6 diagnostic accuracy for EONS diagnosis between 1990 and 2020 including a total of 3276 infants. The range of IL-6 sensitivity and specificity in neonatal samples was 42.1% to 100% and 43% to 100%, the median values were 83% and 83.3%, respectively. IL-6 accuracy was better in preterm infants than in mixed study populations. The sensitivity and specificity in umbilical cord blood was higher than in neonatal peripheral blood, 83% vs 71% and 85% vs 77% respectively. The combination of IL-6 and CRP had a sensitivity in the range of cord blood IL-6 as single measure (84% vs 83%), but far lower specificity (61% vs 85%). Conclusion: IL-6 is a good diagnostic marker of EONS within a study population of preterm infants, with best results for cord blood IL-6 using cut-off values above 30 pg/mL. The biomarker combination of IL-6 and CRP was found to be highly sensitive, but poorly specific. Optimisation of cut-off values, timing of sample collection and positivity criterion of the test could improve the diagnostic value of biomarker combinations.