EARLY-onset neonatal sepsis (EOS) is a life-threatening condition affecting newborns, particularly those born prematurely. However, because early symptoms are often vague and overlap with normal newborn transitions or non-infectious complications, many infants are pre-emptively treated with antibiotics. This widespread use of antibiotics in the absence of confirmed infection raises the risk of antibiotic-related complications and may disrupt healthy development.
A new study suggests that protein biomarkers found in umbilical cord blood may offer a more accurate and timely method for identifying infants truly at risk of EOS. Researchers used tandem mass spectrometry to analyse cord blood samples from preterm infants with and without culture-confirmed EOS. They aimed to discover specific proteins that differed significantly between the two groups and could potentially serve as diagnostic indicators of infection.
The study identified five proteins that were elevated in infants with confirmed EOS. Of these, three, serum amyloid A, C-reactive protein, and lipopolysaccharide-binding protein, were validated using immunoassays. These proteins are known to play a role in inflammatory and immune responses, making them strong candidates for EOS biomarkers.
To assess the clinical utility of these findings, the research team created statistical models including both clinical factors and biomarker levels. A machine learning model, known as a random forest classifier, was trained on data from infants with confirmed EOS. When applied to a separate group of infants who had been treated for presumed sepsis but had no culture-confirmed infection, the model found that most of these infants had biomarker levels resembling those in the control group, suggesting that many may not have needed antibiotics.
These findings highlight the potential of umbilical cord blood analysis to improve diagnostic precision in neonatal care. Early identification of at-risk infants could allow for more targeted antibiotic treatment, helping to reduce unnecessary exposure to antimicrobial agents and their associated risks.
Reference
Mithal LB et al. Cord blood proteomics identifies biomarkers of early-onset neonatal sepsis. JCI Insight. 2025;10(13):e193826.