Introduction: Sepsis is a frequent complication among newborns and accounts for >400,000 deaths globally. Infection-related inflammation contributes to long-term adverse neurodevelopmental outcomes in infants that survive sepsis. Preterm infants, particularly those born < 32 weeks gestational age, are at the highest risk, affecting up to 22%, for developing sepsis. A rapid and accurate diagnosis of sepsis is critical to minimise inflammation and antibiotic therapy, but early diagnosis is complicated by slow (24-36 hours) and variable diagnostic tests. Consequently, 2/3 of infants receive unnecessary antibiotic therapy, which is associated with adverse outcomes, including mortality. Thus, there is an urgent and unmet need for accurate and more rapid adjunct diagnostics to reduce the high prevalence of antibiotic use in this vulnerable population. Proteome differences can be used to identify protein biomarkers that can improve the current diagnostic approach.
Methods: Untargeted label-free quantitative diaPASEF mass-spectrometry based proteomics and targeted immunoassays were used to explore the plasma proteome of preterm human infants born < 29 weeks gestational age with and without sepsis.
Results: In very preterm infants with and without sepsis (n=15 and n=39, respectively), over 500 plasma proteins were identified. Over 70 differentially expressed proteins are associated with sepsis. A panel of protein biomarkers can identify sepsis with high accuracy.
Conclusion: We identified known and novel proteins that are associated with sepsis. On-going analysis suggests that a subset of proteins may have clinical utility as biomarkers for early diagnosis of sepsis in very preterm infants.