title: Host-response biomarkers for diagnosis of late-onset septicemia and necrotizing enterocolitis in preterm infants.
abstract: Preterm infants are highly susceptible to life-threatening infections that are clinically difficult to detect, such as late-onset septicemia and necrotizing enterocolitis (NEC). Here, we used a proteomic approach to identify biomarkers for diagnosis of these devastating conditions. In a case-control study comprising 77 sepsis/NEC and 77 nonsepsis cases (10 in each group being monitored longitudinally), plasma samples collected at clinical presentation were assessed in the biomarker discovery and independent validation phases. We validated the discovered biomarkers in a prospective cohort study with 104 consecutively suspected sepsis/NEC episodes. Proapolipoprotein CII (Pro-apoC2) and a des-arginine variant of serum amyloid A (SAA) were identified as the most promising biomarkers. The ApoSAA score computed from plasma apoC2 and SAA concentrations was effective in identifying sepsis/NEC cases in the case-control and cohort studies. Stratification of infants into different risk categories by the ApoSAA score enabled neonatologists to withhold treatment in 45% and enact early stoppage of antibiotics in 16% of nonsepsis infants. The negative predictive value of this antibiotic policy was 100%. The ApoSAA score could potentially allow early and accurate diagnosis of sepsis/NEC. Upon confirmation by further multicenter trials, the score would facilitate rational prescription of antibiotics and target infants who require urgent treatment.
authors.affiliation: Department of Pediatrics, Prince of Wales Hospital, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Pak Cheung
authors.initials: PC
authors.lastname: Ng
authors.forename: Irene Ling
authors.initials: IL
authors.lastname: Ang
authors.forename: Rossa Wai Kwun
authors.initials: RW
authors.lastname: Chiu
authors.forename: Karen
authors.initials: K
authors.lastname: Li
authors.forename: Hugh Simon
authors.initials: HS
authors.lastname: Lam
authors.forename: Raymond Pui On
authors.initials: RP
authors.lastname: Wong
authors.forename: Kit Man
authors.initials: KM
authors.lastname: Chui
authors.forename: Hon Ming
authors.initials: HM
authors.lastname: Cheung
authors.forename: Eddy Wing Yin
authors.initials: EW
authors.lastname: Ng
authors.forename: Tai Fai
authors.initials: TF
authors.lastname: Fok
authors.forename: Joseph Jao Yiu
authors.initials: JJ
authors.lastname: Sung
authors.forename: Yuk Ming Dennis
authors.initials: YM
authors.lastname: Lo
authors.forename: Terence Chuen Wai
authors.initials: TC
authors.lastname: Poon
mesh_terms: D001053:Apolipoproteins / Q000097:blood / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D020345:Enterocolitis, Necrotizing / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000097:blood / Q000175:diagnosis*; D008297:Male; D040901:Proteomics; D018805:Sepsis / Q000175:diagnosis*
chemical_list: D001053:Apolipoproteins; D015415:Biomarkers; D001798:Blood Proteins; C035165:apolipoprotein SAA