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Updated: Sep 15, 2025
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A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
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Transcriptomic mortality signature defines high-risk neonatal sepsis endotype
Faris N Al Gharaibeh1,2, Min Huang3, James L Wynn4
1Division of Neonatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Frontiers in Immunology
|July 14, 2025
Summary
Gene-expression profiling identified distinct neonatal sepsis endotypes. Endotype A, characterized by neutrophil progenitor dysregulation, showed significantly higher mortality and cardiac dysfunction, suggesting a potential for targeted therapies.
Area of Science:
- Genomics
- Neonatal Medicine
- Immunology
Background:
- Neonatal sepsis is a major cause of death in children globally.
- Limited treatment options exist due to the condition's heterogeneity.
- Gene-expression profiling may reveal sepsis subtypes for targeted treatments.
Purpose of the Study:
- To identify distinct subtypes of neonatal sepsis using gene-expression profiling.
- To determine the clinical relevance of identified subtypes regarding mortality and organ dysfunction.
Main Methods:
- Secondary analysis of public gene-expression datasets.
- Differential gene expression analysis and t-SNE for patient clustering.
- Comparison of mortality and organ dysfunction across identified clusters.
Main Results:
- Three neonatal sepsis endotypes were identified using a 100-gene expression signature.
- Endotype A was associated with significantly higher mortality (22%) and cardiac dysfunction (61%).
- Endotype A pathobiology was driven by neutrophil progenitors and hyperinflammation.
Conclusions:
- Gene-expression profiling can differentiate neonatal sepsis heterogeneity.
- Endotype A represents a high-risk group requiring targeted interventions.
- Subclassification may guide identification of at-risk neonates and therapy selection.
