Genetic Signature in Newborns Predicts Neonatal Sepsis Before Symptoms Appear

Neonatal sepsis, which occurs due to the body’s abnormal response to severe infection within the first 28 days of life, results in approximately 200,000 deaths globally each year. This condition affects around 1.3 million infants worldwide annually, with even higher rates reported in lower- and middle-income countries (LMICs). Diagnosing sepsis poses significant challenges for both healthcare providers and families. The symptoms can resemble those of various other illnesses, and tests to determine the presence of sepsis can take several days, may not always be accurate, and are largely confined to hospital settings. This uncertainty can lead to delays in administering urgent antibiotic treatment. Furthermore, even if treatment is successful, sepsis can cause lifelong consequences, including developmental delays in children, cognitive deficits, and long-term health issues. A new study has now revealed that a genetic signature in newborns can predict neonatal sepsis before any symptoms appear, offering the potential to assist healthcare professionals in diagnosing affected infants earlier, especially in LMICs where neonatal sepsis is a critical issue.

The extensive study was conducted by researchers at The University of British Columbia (UBC, Vancouver, BC, Canada) and Simon Fraser University (SFU, Burnaby, BC, Canada) in The Gambia, where blood samples were collected from 720 infants at birth. Among this cohort, 15 infants developed early-onset sepsis. The researchers employed machine learning techniques to analyze the expression of genes active at birth, seeking biological markers capable of predicting sepsis. The findings, published in eBiomedicine, indicate that the researchers identified four genes that, when combined into a 'signature', could accurately predict sepsis in newborns with a success rate of 90%.

This study presented a unique opportunity, as samples from all infants in the cohort were available on the day of their birth, allowing researchers to investigate the gene expressions in those who later developed sepsis before they exhibited any illness. Most previous studies have only reported markers detected after the infants had already fallen ill, making those findings less useful for prediction. The next phase of this research involves conducting a large prospective study to validate the predictive capability of the signature in other populations and to establish its methodology. Following this, the aim will be to develop point-of-care tools for approval by relevant regulatory bodies. The researchers hope that this genetic signature will eventually be integrated not only into PCR tests in hospitals but also into portable, point-of-care devices.

“There are point-of-care devices available that can test for gene expression, for instance, COVID-19 and influenza, with a single drop of blood. They can operate anywhere with a power source including batteries and can be used by anyone, not just trained healthcare providers,” said co-senior author Dr. Bob Hancock, professor in the UBC department of microbiology and immunology. “These portable devices could be retooled to recognize this ‘signature’ relatively easily and inexpensively.”

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