Abstract
Background
Early-onset sepsis (EOS) remains a substantial cause of morbidity and mortality among neonates. Yet, currently available biological parameters have not proven to be accurate enough to predict EOS reliably. This study aimed to determine serum concentrations of 13 cytokines in umbilical cord blood and evaluate their diagnostic value for EOS.
Methods
A prospective single-center study that included analysis of umbilical cord blood of term and preterm neonates who were born from March 2017 to November 2017. Using ELISA analysis, 13 cytokines were simultaneously quantified and correlated with the development of EOS.
Results
Four hundred and seventy-four neonates were included, of which seven met the criteria for culture-positive EOS. Interleukin (IL)-6 (p < 0.001), IL-9 (p = 0.003), and IL-21 (p < 0.001) were significantly increased in neonates with EOS compared to controls. Sensitivity and specificity for IL-6, IL-9, and IL-21 at the defined cut-off points were 85.7 and 77.3%, 71.4 and 62.5%, and 71.4 and 52.0%, respectively.
Conclusions
In neonates with EOS, IL-9 and IL-21 are significantly elevated and may be employed in the diagnostic of EOS. However, diagnostic accuracy remains lower than with IL-6. Values of 13 T cell cytokines may be used as reference values for future studies in neonates.
Impact
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Interleukin-9 (IL-9) and interleukin-21 (IL-21) are significantly elevated in neonates with early-onset sepsis.
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IL-9 and IL-21 have been shown to play a specific role in neonatal sepsis.
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Neonatal reference values were generated for several cytokines.
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IL-9 and IL-21 might be attractive biomarkers for neonatal sepsis in future. This study is likely to promote further research in this area.
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Values of several T cell cytokines may be used as reference values for future studies in neonates.
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Contributions
G.M.F. assisted in conceptualizing the study, carried out statistical analyses, interpreted data, and drafted the initial manuscript. T.B. performed laboratory analysis of the cord blood, interpreted data, and assisted in the drafting of the manuscript. M.B. interpreted the data and assisted in the drafting of the manuscript. S.H. assisted in conceptualizing the study and interpreted the data. D.S. assisted in conceptualizing the study and interpreted the data. C.U.E. conceptualized and designed the study, collected data, carried out statistical analyses, interpreted data, and drafted the initial manuscript. All authors reviewed and revised the manuscript, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work.
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Froeschle, G.M., Bedke, T., Boettcher, M. et al. T cell cytokines in the diagnostic of early-onset sepsis. Pediatr Res (2020). https://doi.org/10.1038/s41390-020-01248-x
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