Pancreatic stone protein as a novel marker for neonatal sepsis
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Early-onset sepsis (EOS) is one of the main causes for the admission of newborns to the neonatal intensive care unit. However, traditional infection markers are poor diagnostic markers of EOS. Pancreatic stone protein (PSP) is a promising sepsis marker in adults. The aim of this study was to investigate whether determining PSP improves the diagnosis of EOS in comparison with other infection markers.
This was a prospective multicentre study involving 137 infants with a gestational age of >34 weeks who were admitted with suspected EOS. PSP, procalcitonin (PCT), soluble human triggering receptor expressed on myeloid cells-1 (sTREM-1), macrophage migration inhibitory factor (MIF) and C-reactive protein (CRP) were measured at admission. Receiver-operating characteristic (ROC) curve analysis was performed.
The level of PSP in infected infants was significantly higher than that in uninfected ones (median 11.3 vs. 7.5 ng/ml, respectively; p = 0.001). The ROC area under the curve was 0.69 [95 % confidence interval (CI) 0.59–0.80; p < 0.001] for PSP, 0.77 (95 % CI 0.66–0.87; p < 0.001) for PCT, 0.66 (95 % CI 0.55–0.77; p = 0.006) for CRP, 0.62 (0.51–0.73; p = 0.055) for sTREM-1 and 0.54 (0.41–0.67; p = 0.54) for MIF. PSP independently of PCT predicted EOS (p < 0.001), and the use of both markers concomitantly significantly increased the ability to diagnose EOS. A bioscore combining PSP (>9 ng/ml) and PCT (>2 ng/ml) was the best predictor of EOS (0.83; 95 % CI 0.74–0.93; p < 0.001) and resulted in a negative predictive value of 100 % and a positive predictive value of 71 %.
In this prospective study, the diagnostic performance of PSP and PCT was superior to that of traditional markers and a combination bioscore improved the diagnosis of sepsis. Our findings suggest that PSP is a valuable biomarker in combination with PCT in EOS.
KeywordsC-reactive protein Infant Macrophage migration inhibitory factor Pancreatic stone protein Procalcitonin Sepsis sTREM-1
Area under the curve
Immature by total ratio
Macrophage migration inhibiting factor
Pancreatic stone protein
Soluble human triggering receptor expressed on myeloid cells-1
White blood cell count
The authors thank Claudia Schad (Division of Neonatology, University of Bern, Switzerland) for help in data acquisition; Martha Bain (University Hospital Zurich, Switzerland) for excellent technical support with PSP measurements; Silvia Rihs and Leslie Saurer (Department of Pathology, University of Bern, Switzerland) for help in performing sTREM-1 ELISA; Fred C. G. J. Sweep (Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands) for kindly providing antibodies used in the MIF ELISA; Marlies Knaup Reymond (Infectious Diseases Service, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland) for performing the MIF ELISA. This study was funded by a grant from the Vinetum Foundation, Biel, Switzerland (LJS) and supported by grants from the Swiss National Science Foundation (TR, Grant 310030_138488) and the Amelie Waring Foundation, Zurich, Switzerland (RG).
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