Identifying novel markers of late onset neonatal sepsis using proteomic analysis

Background: Late onset sepsis remains a significant source of morbidity and mortality for newborn infants. Early detection and treatment of those with true sepsis, and limiting antibiotic exposure in those infants ultimately proven to be non-septic, remains paramount. We sought to identify novel markers of late-onset sepsis in newborn infants. Method: Infants of any gestation admitted to the Neonatal and Paediatric ICU, older than 48 hours, suspected of late-onset sepsis, and deemed to require antibiotics were eligible with parental consent. Infants were categorised into: non-septic (negative blood culture and normal markers), clinical sepsis (negative blood culture with positive markers), and confirmed sepsis (positive blood culture) groups. A 3 ul aliquot of serum was trypsinized and peptides were analysed by mass spectrometry. Results: Twenty two infants were recruited from 2010 to 2013 with median birth gestation 27.5 weeks (IQR 25.3, 30.8), age 11 days (IQR 9, 13), birth weight 1062g (IQR 1145, 1475). Sepsis was confirmed in 9 (41%), clinical sepsis in 6 (27%), and 7 (32%) were non-septic. Relative quantitation of ~100 proteins based on spectral counts was obtained. Principal component analysis distinguished between confirmed and non-septic infants. Principal component 1 (PC-1) accounted for 23% of the variation between samples and 17 proteins had PC-1 loading scores > 0.1 or < -0.1 (Table 1). Conclusions: Proteomic analysis shows potential to discriminate between septic and non-septic infants, and identify novel markers of late-onset neonatal sepsis in larger study cohorts.