European Journal of Pediatrics

, Volume 177, Issue 5, pp 625–632 | Cite as

The diagnostic accuracy of presepsin in neonatal sepsis: a meta-analysis

  • Ioannis Bellos
  • Georgia Fitrou
  • Vasilios Pergialiotis
  • Nikolaos Thomakos
  • Despina N. Perrea
  • Georgios Daskalakis


There is growing evidence that presepsin is a promising biomarker in the diagnosis of sepsis in adults. The objective of our study is to investigate current evidence related to the diagnostic accuracy of presepsin in neonatal sepsis. To accomplish this, we searched the Medline (1966–2017), Scopus (2004–2017), (2008–2017), EMBASE (1980–2017), Cochrane Central Register of Controlled Trials CENTRAL (1999–2017), and Google Scholar (2004–2017) databases. Eleven studies were included in the present meta-analysis, with a total number of 783 neonates. The pooled sensitivity of serum presepsin for the prediction of neonatal sepsis was 0.91 (95% CI [0.87–0.93]) and the pooled specificity was 0.91 (95% CI [0.88–0.94]). The diagnostic odds ratio was 170.28 (95% CI [51.13–567.11]) and the area under the curve (AUC) was 0.9751 (SE 0.0117). Head-to-head comparison with AUC values of C-reactive protein (0.9748 vs. 0.8580) and procalcitonin (0.9596 vs. 0.7831) revealed that presepsin was more sensitive in detecting neonatal sepsis.

Conclusion: Current evidence support the use of presepsin in the early neonatal period in high-risk populations as its diagnostic accuracy seems to be high in detecting neonatal sepsis.

What is known:

Neonatal sepsis is a leading cause of morbidity and mortality.

Current laboratory tests cannot accurately discriminate endangered neonates.

What is new:

The diagnostic odds ratio of presepsin is 170.28 and the area under the curve is 0.9751.

According to our meta-analysis, presepsin is a useful protein that may help clinicians identify neonates at risk.


Presepsin CD14 sCD14-ST Neonatal sepsis Meta-analysis 


95% CI

95% confidence interval


Area under the curve


Diagnostic odds ratio


Early-onset sepsis


Late-onset sepsis


Lipopolysaccharide-lipopolysaccharide binding protein


Preferred Reporting Items for Systematic Reviews and Meta-Analyses


Soluble CD14 subtype


Standard error


Summary receiver operating characteristic


Authors’ Contributions

Ioannis Bellos performed the meta-analysis and conducted the electronic search.

Georgia Fitrou conducted the electronic search and tabulated the data.

Vasilios Pergialiotis conceived the idea, formed the tables, designed the statistical analysis, and wrote the manuscript.

Despina N. Perrea performed the sensitivity and meta-regression analysis and wrote the manuscript.

Nikolaos Thomakos tabulated data and wrote the manuscript.

Georgios Daskalakis conceived the idea, wrote, and revised the manuscript.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Informed consent

The present systematic review and meta-analysis is based on aggregated data that were retrieved from studies already retrieved. We did not collect individual patient data and did not have direct contact with patients included.

Supplementary material

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ESM 1 (DOC 64 kb)


  1. 1.
    Adams-Chapman I, Stoll BJ (2006) Neonatal infection and long-term neurodevelopmental outcome in the preterm infant. Curr Opin Infect Dis 19(3):290–297. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC (2016) The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315(8):801–810. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Bakhuizen SE, de Haan TR, Teune MJ, van Wassenaer-Leemhuis AG, van der Heyden JL, van der Ham DP, Mol BW (2014) Meta-analysis shows that infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications. Acta Paediatr 103(12):1211–1218. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Chiesa C, Panero A, Osborn JF, Simonetti AF, Pacifico L (2004) Diagnosis of neonatal sepsis: a clinical and laboratory challenge. Clin Chem 50(2):279–287. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Shabuj KH, Hossain J, Moni SC, Dey SK (2017) C-reactive protein (CRP) as a single biomarker for diagnosis of neonatal sepsis: a comprehensive meta-analysis. Mymensingh Med J 26(2):364–371PubMedPubMedCentralGoogle Scholar
  6. 6.
    Pontrelli G, De Crescenzo F, Buzzetti R, Jenkner A, Balduzzi S, Calo Carducci F, Amodio D, De Luca M, Chiurchiu S, Davies EH, Copponi G, Simonetti A, Ferretti E, Di Franco V, Rasi V, Della Corte M, Gramatica L, Ciabattini M, Livadiotti S, Rossi P (2017) Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and children with systemic inflammatory syndrome: a meta-analysis. BMC Infect Dis 17(1):302. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Kuzniewicz MW, Puopolo KM, Fischer A, Walsh EM, Li S, Newman TB, Kipnis P, Escobar GJ (2017) A quantitative, risk-based approach to the management of neonatal early-onset sepsis. JAMA Pediatr 171(4):365–371. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Zhou M, Cheng S, Yu J, Lu Q (2015) Interleukin-8 for diagnosis of neonatal sepsis: a meta-analysis. PLoS One 10(5):e0127170. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Memar MY, Alizadeh N, Varshochi M, Kafil HS (2017) Immunologic biomarkers for diagnostic of early-onset neonatal sepsis. J Matern Fetal Neonatal Med:1–11.
  10. 10.
    Zou Q, Wen W, Zhang XC (2014) Presepsin as a novel sepsis biomarker. World J Emerg Med 5(1):16–19. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Chenevier-Gobeaux C, Borderie D, Weiss N, Mallet-Coste T, Claessens YE (2015) Presepsin (sCD14-ST), an innate immune response marker in sepsis. Clin Chim Acta 450:97–103. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Wu CC, Lan HM, Han ST, Chaou CH, Yeh CF, Liu SH, Li CH, Blaney GN 3rd, Liu ZY, Chen KF (2017) Comparison of diagnostic accuracy in sepsis between presepsin, procalcitonin, and C-reactive protein: a systematic review and meta-analysis. Ann Intensive Care 7(1):91. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62(10):e1–34. CrossRefGoogle Scholar
  14. 14.
    Weston EJ, Pondo T, Lewis MM, Martell-Cleary P, Morin C, Jewell B, Daily P, Apostol M, Petit S, Farley M, Lynfield R, Reingold A, Hansen NI, Stoll BJ, Shane AL, Zell E, Schrag SJ (2011) The burden of invasive early-onset neonatal sepsis in the United States, 2005–2008. Pediatr Infect Dis J 30(11):937–941. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Quinn JA, Munoz FM, Gonik B, Frau L, Cutland C, Mallett-Moore T, Kissou A, Wittke F, Das M, Nunes T, Pye S, Watson W, Ramos AA, Cordero JF, Huang WT, Kochhar S, Buttery J, Brighton Collaboration Preterm Birth Working Group (2016) Preterm birth: case definition and guidelines for data collection, analysis, and presentation of immunisation safety data. Vaccine 34(49):6047–6056. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, Leeflang MM, Sterne JA, Bossuyt PM, Group Q (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155(8):529–536. CrossRefPubMedGoogle Scholar
  17. 17.
    Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A (2006) Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol 6:31. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Walter SD (2002) Properties of the summary receiver operating characteristic (SROC) curve for diagnostic test data. Stat Med 21(9):1237–1256. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Galbraith RF (1988) A note on graphical presentation of estimated odds ratios from several clinical trials. Stat Med 7(8):889–894CrossRefPubMedCentralGoogle Scholar
  20. 20.
    Deeks JJ, Macaskill P, Irwig L (2005) The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol 58(9):882–893. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Montaldo P, Rosso R, Santantonio A, Chello G, Giliberti P (2017) Presepsin for the detection of early-onset sepsis in preterm newborns. Pediatr Res 81(2):329–334. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Xiao T, Chen LP, Zhang LH, Lai FH, Zhang L, Qiu QF, Que RL, Xie S, Wu DC (2017) The clinical significance of sCD14-ST for blood biomarker in neonatal hematosepsis: a diagnostic accuracy study. Medicine (Baltimore) 96(18):e6823. CrossRefGoogle Scholar
  23. 23.
    Tabl HA, Abed NT (2016) Diagnostic value of presepsin in neonatal sepsis. Egypt J Immunol 23(2):29–37PubMedPubMedCentralGoogle Scholar
  24. 24.
    Ozdemir AA, Elgormus Y (2017) Diagnostic value of presepsin in detection of early-onset neonatal sepsis. Am J Perinatol 34(6):550–556. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Topcuoglu S, Arslanbuga C, Gursoy T, Aktas A, Karatekin G, Uluhan R, Ovali F (2016) Role of presepsin in the diagnosis of late-onset neonatal sepsis in preterm infants. J Matern Fetal Neonatal Med 29(11):1834–1839. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Sabry J, Elfeky O, Elsadek A, Eldaly A (2016) Presepsin as an early reliable diagnostic and prognostic marker of neonatal sepsis. Int J Adv Res 4(6):1538–1549CrossRefGoogle Scholar
  27. 27.
    Mussap M, Puxeddu E, Puddu M, Ottonello G, Coghe F, Comite P, Cibecchini F, Fanos V (2015) Soluble CD14 subtype (sCD14-ST) presepsin in premature and full term critically ill newborns with sepsis and SIRS. Clin Chim Acta 451(Pt A):65–70. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Poggi C, Bianconi T, Gozzini E, Generoso M, Dani C (2015) Presepsin for the detection of late-onset sepsis in preterm newborns. Pediatrics 135(1):68–75. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Saied Osman A, Goudah Awadallah M, Tabl HAEL-M, Samir Saad Goudah E (2015) Presepsin as a novel diagnostic marker in neonatal septicemia. Egypt J Med Microbiol 24(3):21–26CrossRefGoogle Scholar
  30. 30.
    Mostafa R, Kholouss S, Nea M (2015) Detection of presepsin and surface CD14 as a biomarker for early diagnosis of neonatal sepsis. J Am Sci 1111(1010):104–116Google Scholar
  31. 31.
    Motalib T, Khalaf F, Hendawy GE, Kotb S, Ali A, Sharnoby AE (2015) Soluble CD14-subtype (prespsin) and hepcidin as diagnostic and prognostic markers in early onset neonatal sepsis. Egypt J Med Microbiol 24(3)Google Scholar
  32. 32.
    Astrawinata D (2017) The role of Presepsin, C-reactive protein and procalcitonin as a marker of therapy response and prognosis for late onset neonatal sepsis in preterm neonates. J Med Sci Clin Res 5(8)Google Scholar
  33. 33.
    Pavcnik-Arnol M, Hojker S, Derganc M (2007) Lipopolysaccharide-binding protein, lipopolysaccharide, and soluble CD14 in sepsis of critically ill neonates and children. Intensive Care Med 33(6):1025–1032. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Małgorzata S, Jakub B, Szymańska A, Pukas-Bochenek A, Stachurska A, Godula-Stuglik U (2015) Diagnostic value of presepsin (Scd14-St subtype) evaluation in the detection of severe neonatal infections. Int J Res Stud Biosci 3(1):110–116Google Scholar
  35. 35.
    Xiao T, Chen LP, Liu H, Xie S, Luo Y, Wu DC (2017) The analysis of etiology and risk factors for 192 cases of neonatal sepsis. Biomed Res Int 2017:8617076. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Chen L, Xiao T, Luo Y, Qiu Q, Que R, Huang X, Wu D (2017) Soluble CD14 subtype (sCD14-ST) is a biomarker for neonatal sepsis. Int J Clin Exp Pathol 10(9):9718–9724Google Scholar
  37. 37.
    Iroh Tam PY, Bendel CM (2017) Diagnostics for neonatal sepsis: current approaches and future directions. Pediatr Res 82(4):574–583. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Connell TG, Rele M, Cowley D, Buttery JP, Curtis N (2007) How reliable is a negative blood culture result? Volume of blood submitted for culture in routine practice in a children’s hospital. Pediatrics 119(5):891–896. CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Pugni L, Pietrasanta C, Milani S, Vener C, Ronchi A, Falbo M, Arghittu M, Mosca F (2015) Presepsin (soluble CD14 subtype): reference ranges of a new sepsis marker in term and preterm neonates. PLoS One 10(12):e0146020. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Dai J, Jiang W, Min Z, Yang J, Tan Y, Ma T, Ge Z (2017) Neutrophil CD64 as a diagnostic marker for neonatal sepsis: meta-analysis. Adv Clin Exp Med 26(2):327–332. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Ioannis Bellos
    • 1
  • Georgia Fitrou
    • 1
  • Vasilios Pergialiotis
    • 1
    • 2
  • Nikolaos Thomakos
    • 3
  • Despina N. Perrea
    • 1
  • Georgios Daskalakis
    • 3
  1. 1.Laboratory of Experimental Surgery and Surgical Research N.S. ChristeasNational and Kapodistrian University of AthensAthensGreece
  2. 2.ChalandriGreece
  3. 3.First Department of Obstetrics and Gynecology, Alexandra HospitalNational and Kapodistrian University of AthensAthensGreece

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