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Biomarkers estimating baseline mortality risk for neonatal sepsis: nPERSEVERE: neonate-specific sepsis biomarker risk model

Pediatric Research volume 94, pages 1451–1456 (2023)Cite this article

Abstract

Background

Prognostic biomarker research neonatal sepsis is lacking. We assessed the utility of a validated pediatric prognostic tool called PERSEVERE II that uses decision tree methodology to predict mortality at discharge in neonates who experienced sepsis.

Methods

Prospective study in a dual-center cohort of neonates with sepsis admitted between June 2020 and December 2021. Biomarker analysis was done on serum samples obtained at the time of evaluation for the event.

Results

In a cohort of 59 neonates with a mortality rate of 15.3%, PERSEVERE II was 67% sensitive and 59% specific for mortality, p 0.27. Amongst PERSEVERE II biomarkers, IL-8 showed good prognostic performance for mortality prediction with a cutoff of 300 pg/mL (sensitivity 100%, specificity 65%, negative predictive value 100%, AUC 0.87, p 0.0003). We derived a new decision tree that is neonate specific (nPERSEVERE) with improved performance compared to IL-8 (sensitivity 100%, specificity 86%, negative predictive value 100%, AUC 0.95, p < 0.0001).

Conclusions

IL-8 and nPERSEVERE demonstrated good prognostic performance in a small cohort of neonates with sepsis. Moving toward precision medicine in sepsis, our study proposes an important tool for clinical trial prognostic enrichment that needs to be validated in larger studies.

Impact

  • Prognostic and predictive biomarker research is lacking in the newborn intensive care unit.

  • Biomarkers can be used at the time of evaluation for neonatal sepsis (blood culture acquisition) to identify neonates with high baseline mortality risk.

  • Stratification is an important step toward precision medicine in neonatal sepsis.

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Fig. 1: Study flowchart.
Fig. 2: IL-8 is a candidate biomarker for mortality prediction.
Fig. 3: The pruned final version of nPERSEVERE.
Fig. 4: Survival trends of neonates according to nPERSEVERE classification.

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Data availability

Datasets generated from this work are available upon reasonable request to the corresponding author.

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Acknowledgements

Near the end of this work, Dr Hector R. Wong passed away unexpectedly. He was a good mentor, friend, husband, father, and physician scientist. He will be forever remembered by those who had the privilege to work with him. We also appreciate Dr Basillia Zingarelli for reviewing the final drafts of the manuscript and Andrew M. Smith for his input on the analysis. Some of the figures were generated using www.BioRender.com.

Funding

This presented work is supported by Dr Wong’s R35GM126943 grant from the NIH.

Author information

Authors and Affiliations

  1. Division of Neonatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Faris N. Al Gharaibeh

  2. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Faris N. Al Gharaibeh, Matthew N. Alder & Hector R. Wong

  3. Division of Critical Care, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Patrick Lahni, Matthew N. Alder & Hector R. Wong

Authors
  1. Faris N. Al Gharaibeh
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Contributions

F.N.A., M.N.A., and H.R.W. conceptualized and designed the study, performed the statistical analyses, and reviewed the data generated. P.L. conducted the Luminex assays to obtain serum biomarker levels. F.N.A drafted the initial manuscript, and F.N.A and M.N.A. reviewed and revised the manuscript. All authors approved the work submitted in this manuscript and are accountable for all aspects of this work.

Corresponding author

Correspondence to Faris N. Al Gharaibeh.

Ethics declarations

Competing interests

Cincinnati Children’s Research foundation and Hector Wong hold U.S. patents for the PERSEVERE biomarkers. Cincinnati Children’s Research foundation and F.N.A. have filed for a U.S. patent for nPERSEVERE.

Ethics approval and consent to participate

This study was reviewed by the institutional review board at Cincinnati Children’s Hospital Medical Center and the University of Cincinnati and consent was waived.

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Al Gharaibeh, F.N., Lahni, P., Alder, M.N. et al. Biomarkers estimating baseline mortality risk for neonatal sepsis: nPERSEVERE: neonate-specific sepsis biomarker risk model. Pediatr Res 94, 1451–1456 (2023). https://doi.org/10.1038/s41390-022-02414-z

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