A GROUNDBREAKING study has identified a genetic signature capable of predicting early-onset sepsis (EOS) in newborns, providing hope for faster and more effective treatment of this life-threatening condition.
Neonatal sepsis, a severe infection in the bloodstream, is particularly challenging to diagnose early due to its subtle, non-specific symptoms. This delay often leads to critical treatment gaps, making early gene expression biomarkers essential for timely intervention.
In a collaborative study conducted in two hospitals in The Gambia, West Africa, researchers examined gene expression profiles of 720 full-term, healthy newborns from 2017–2019. Among these, 21 neonates were later hospitalised with sepsis within their first month, with cases split into early-onset (within 7 days) and late-onset sepsis (between 8–28 days). An additional 12 newborns were hospitalised for localised infections that did not progress to sepsis, and 33 healthy newborns served as a control group.
Researchers used RNA sequencing on blood samples taken at birth, when all newborns appeared healthy, and again within the first week to track gene expression changes. In neonates who later developed EOS, the team identified nearly 1,000 differentially expressed genes at birth compared to those who remained healthy or developed only localised infections. Using machine learning models, the researchers isolated a 4-gene signature, HSPH1, BORA, NCAPG2, and PRIM, that predicted EOS with impressive accuracy (area under the curve [AUC]: 0.94, sensitivity: 0.93, specificity: 0.92). Notably, these findings were validated in an external cohort of newborns, proving the robustness of this genetic marker (validation AUC: 0.72, sensitivity: 0.83, specificity: 0.83).
This 4-gene predictive signature for EOS could enable early intervention before clinical presentation of sepsis symptoms, providing critical timely treatment of newborns and helping mitigate the long-term sequelae of sepsis.
Reference
An AY et al. Predictive gene expression signature diagnoses neonatal sepsis before clinical presentation. EBioMedicine. 2024; DOI:10.1016/j.ebiom.2024.105411.
