Examining Transcriptomic Markers Associated With Neutrophil Extracellular Traps to Predict Mortality Risk in Neonatal...

Area of Science:

• Neonatal immunology
• Molecular diagnostics
• Coagulation disorders

Background:

• Neonates are vulnerable to sepsis and associated fatal coagulopathy.
• Current anticoagulant therapies show limited efficacy in sepsis, possibly due to patient variability.
• Neutrophil extracellular traps (NETs) influence coagulation, suggesting NET-specific biomarkers could personalize treatment.

Purpose of the Study:

• To evaluate the association between NET gene expression and adverse outcomes in neonatal sepsis.
• To develop and validate a predictive model for neonatal sepsis outcomes based on NETs.

Main Methods:

• Whole blood transcriptomes from 123 neonates with sepsis were analyzed.
• A predictive model, the NET score, was developed using NET-related gene expression.
• Model performance was validated in independent datasets; mediation and temporal analyses explored NETosis-coagulation interactions.

Main Results:

• The NET score demonstrated strong predictive performance with AUCs of 88.7% and 85.4% in validation sets.
• Analyses supported a sequential relationship between NETosis and coagulation in sepsis.
• The model's age-specificity was confirmed across pediatric and adult sepsis datasets.

Conclusions:

• The NET score offers a novel risk stratification tool for neonatal sepsis.
• It identifies neonates at high risk for sepsis-associated coagulopathy and poor outcomes.
• This approach may guide the development of targeted therapeutic strategies.