Skip to main content

Advertisement

SpringerLink
Log in

Soluble TREM-1 as a predictive factor of neonatal sepsis: a meta-analysis

  • Review
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Background

The efficacy of soluble triggering receptor expressed on myeloid cell-1 (TREM-1) in detecting sepsis in adults has already been proven. To date, however, consensus in the field of neonatal sepsis is lacking. The purpose of the present systematic review is to accumulate current evidence in this field.

Search strategy

We systematically searched Medline (1966–2017), Scopus (2004–2017), Clinicaltrials.gov (2008–2017), EMBASE (1980–2017), Cochrane Central Register of Controlled Trials CENTRAL (1999–2017) and Google Scholar (2004–2017) along with reference lists from included studies.

Main results

Eight studies were finally included in the present analysis, with a total number of 667 neonates. The estimated sensitivity for the summary point was 0.95 [95% CI (0.81–0.99)] and the specificity was 0.87 [95% CI (0.56–0.97)]. The diagnostic odds ratio was calculated at 132.49 [95% CI (6.85–2560.70)]. Fagan’s nomogram demonstrated that the post-test probability increased to 71% and decreased to 2%, when the pre-test probability was set at 25%. However, significant discrepancy was observed in terms of the used cut-offs; therefore, the sensitivity and specificity presented in our meta-analysis should be reviewed with caution, as they may present an overestimation of the actual predictive efficacy of this protein.

Conclusion

Current evidence suggests that sTREM-1 may become a useful biomarker for the prediction of neonatal sepsis. However, the small number of studies and the variation of the threshold values limit its implementation in clinical practice. Future large-scale studies are needed to determine the optimal cut-off value that may discriminate normal levels from those suggestive of the presence of neonatal sepsis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Shane AL, Sanchez PJ, Stoll BJ. Neonatal sepsis. Lancet. 2017;390:1770–80.

    Article  PubMed  Google Scholar 

  2. Bakhuizen SE, de Haan TR, Teune MJ, van Wassenaer-Leemhuis AG, van der Heyden JL, van der Ham DP, et al. Meta-analysis shows that infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications. Acta Paediatr. 2014;103:1211–8.

    Article  PubMed  Google Scholar 

  3. Verstraete EH, Blot K, Mahieu L, Vogelaers D, Blot S. Prediction models for neonatal health care-associated sepsis: a meta-analysis. Pediatrics. 2015;135:e1002–14.

    Article  PubMed  Google Scholar 

  4. Kuzniewicz MW, Puopolo KM, Fischer A, Walsh EM, Li S, Newman TB, et al. A quantitative, risk-based approach to the management of neonatal early-onset sepsis. JAMA Pediatr. 2017;171:365–71.

    Article  PubMed  Google Scholar 

  5. Su H, Chang SS, Han CM, Wu KY, Li MC, Huang CY, et al. Inflammatory markers in cord blood or maternal serum for early detection of neonatal sepsis-a systemic review and meta-analysis. J Perinatol. 2014;34:268–74.

    Article  PubMed  CAS  Google Scholar 

  6. Sugitharini V, Prema A, Berla Thangam E. Inflammatory mediators of systemic inflammation in neonatal sepsis. Inflamm Res. 2013;62:1025–34.

    Article  PubMed  CAS  Google Scholar 

  7. Zhou M, Cheng S, Yu J, Lu Q. Interleukin-8 for diagnosis of neonatal sepsis: a meta-analysis. PLoS One. 2015;10:e0127170.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Dai J, Jiang W, Min Z, Yang J, Tan Y, Ma T, et al. Neutrophil CD64 as a diagnostic marker for neonatal sepsis: Meta-analysis. Adv Clin Exp Med. 2017;26:327–32.

    PubMed  Google Scholar 

  9. Cao C, Gu J, Zhang J. Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential biomarker for the diagnosis of infectious diseases. Front Med. 2017;11:169–77.

    Article  PubMed  Google Scholar 

  10. Bouchon A, Facchetti F, Weigand MA, Colonna M. TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature. 2001;410:1103–7.

    Article  PubMed  CAS  Google Scholar 

  11. Tessarz AS, Cerwenka A. The TREM-1/DAP12 pathway. Immunol Lett. 2008;116:111–6.

    Article  PubMed  CAS  Google Scholar 

  12. Weiss G, Lai C, Fife ME, Grabiec AM, Tildy B, Snelgrove RJ, et al. Reversal of TREM-1 ectodomain shedding and improved bacterial clearance by intranasal metalloproteinase inhibitors. Mucosal Immunol. 2017;10:1021–30.

    Article  PubMed  CAS  Google Scholar 

  13. Ye W, Hu Y, Zhang R, Ying K. Diagnostic value of the soluble triggering receptor expressed on myeloid cells-1 in lower respiratory tract infections: a meta-analysis. Respirology. 2014;19:501–7.

    Article  PubMed  Google Scholar 

  14. Su L, Liu D, Chai W, Liu D, Long Y. Role of sTREM-1 in predicting mortality of infection: a systematic review and meta-analysis. BMJ Open. 2016;6:e010314.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62:e1–34.

    Article  PubMed  Google Scholar 

  16. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 2011; 155:529–36.

    Article  PubMed  Google Scholar 

  17. Macaskill P, Gatsonis C, Deeks J, Harbord R, Takwoingi Y. Cochrane handbook for systematic reviews of diagnostic test accuracy chap. 10 analysing and presenting results. 2010.

  18. Sarafidis K, Soubasi-Griva V, Piretzi K, Thomaidou A, Agakidou E, Taparkou A, et al. Diagnostic utility of elevated serum soluble triggering receptor expressed on myeloid cells (sTREM)-1 in infected neonates. Intensive Care Med. 2010;36:864–8.

    Article  PubMed  CAS  Google Scholar 

  19. Schlapbach LJ, Graf R, Woerner A, Fontana M, Zimmermann-Baer U, Glauser D, et al. Pancreatic stone protein as a novel marker for neonatal sepsis. Intensive Care Med. 2013;39:754–63.

    Article  PubMed  CAS  Google Scholar 

  20. Adly AA, Ismail EA, Andrawes NG, El-Saadany MA. Circulating soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as diagnostic and prognostic marker in neonatal sepsis. Cytokine. 2014;65:184–91.

    Article  PubMed  CAS  Google Scholar 

  21. Stein M, Schachter-Davidov A, Babai I, Tasher D, Somekh E. The accuracy of C-reactive protein, procalcitonin, and s-TREM-1 in the prediction of serious bacterial infection in neonates. Clin Pediatr (Phila) 2015; 54:439–44.

    Article  Google Scholar 

  22. El-Gendy F, El-Nemr F, Midan D, El-Din Habib M, Metwally M. Value of measurement of sTREM-1 factor in diagnosis and prognosis of neonatal sepsis. Savant J Med Med Sci. 2015;1:022–9.

    Google Scholar 

  23. Saldir M, Tunc T, Cekmez F, Cetinkaya M, Kalayci T, Fidanci K, et al. Endocan and soluble triggering receptor expressed on myeloid cells-1 as novel markers for neonatal sepsis. Pediatr Neonatol 2015; 56:415–21.

    Article  PubMed  Google Scholar 

  24. El-khier N, Nassar D, AbdelAal SD, Abdel-Hady H-S. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as a diagnostic and prognostic marker of late-onset sepsis in preterm neonates. Int J Adv Res. 2016;4:123–31.

    Article  CAS  Google Scholar 

  25. Zidan M, Kamal H, El-Behisy M, Haie O, Nasser M. Serum triggering receptor expressed on myloid cells-1 (sTREM-1) and its role in diagnosis of neonatal sepsis. Med J Cairo Univ. 2016;84:17–25.

    Google Scholar 

  26. Arizaga-Ballesteros V, Alcorta-Garcia MR, Lazaro-Martinez LC, Amezquita-Gomez JM, Alanis-Cajero JM, Villela L, et al. Can sTREM-1 predict septic shock and death in late-onset neonatal sepsis? A pilot study. Int J Infect Dis. 2015;30:27–32.

    Article  PubMed  CAS  Google Scholar 

  27. Mazzucchelli I, Garofoli F, Ciardelli L, Borghesi A, Tzialla C, Di Comite A, et al. Diagnostic performance of triggering receptor expressed on myeloid cells-1 and CD64 index as markers of sepsis in preterm newborns. Pediatr Crit Care Med. 2013;14:178–82.

    Article  PubMed  Google Scholar 

  28. Stoll BJ, Hansen NI, Adams-Chapman I, Fanaroff AA, Hintz SR, Vohr B, et al. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA. 2004;292:2357–65.

    Article  PubMed  CAS  Google Scholar 

  29. Vouloumanou EK, Plessa E, Karageorgopoulos DE, Mantadakis E, Falagas ME. Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and meta-analysis. Intensive Care Med 2011; 37:747–62.

    Article  PubMed  CAS  Google Scholar 

  30. Shabuj KH, Hossain J, Moni SC, Dey SK. C-reactive protein (CRP) as a single biomarker for diagnosis of neonatal sepsis: a comprehensive meta-analysis. Mymensingh Med J. 2017;26:364–71.

    PubMed  CAS  Google Scholar 

  31. Sharma D, Farahbakhsh N, Shastri S, Sharma P. Biomarkers for diagnosis of neonatal sepsis: a literature review. J Matern Fetal Neonatal Med 2018;31:1646–59.

    Article  PubMed  Google Scholar 

  32. Deleon C, Shattuck K, Jain S. Biomarkers of neonatal sepsis Neoreviews. 2015;16:e297–e308.

    Article  Google Scholar 

  33. Bhandari V. Effective biomarkers for diagnosis of neonatal sepsis. J Pediatric Infect Dis Soc. 2014;3:234–45.

    Article  PubMed  Google Scholar 

  34. Memar MY, Alizadeh N, Varshochi M, Kafil HS. Immunologic biomarkers for diagnostic of early-onset neonatal sepsis. J Matern Fetal Neonatal Med 2017:1–11.

  35. Bhan C, Dipankar P, Chakraborty P, Sarangi PP. Role of cellular events in the pathophysiology of sepsis. Inflamm Res. 2016;65:853–68.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Second Department of Obstetrics and Gynecology, Attikon University Hospital, National and Kapodistrian University of Athens, 6, Danaidon str., 15232, Chalandri, Greece

    Ioannis Bellos, Georgia Fitrou, Nikolaos Thomakos, Nikolaos Papantoniou & Vasilios Pergialiotis

  2. First Department of Obstetrics and Gynecology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece

    Georgios Daskalakis & Nikolaos Thomakos

Authors
  1. Ioannis Bellos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Georgia Fitrou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Georgios Daskalakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nikolaos Thomakos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nikolaos Papantoniou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vasilios Pergialiotis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vasilios Pergialiotis.

Additional information

Responsible Editor: Artur Bauhofer.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bellos, I., Fitrou, G., Daskalakis, G. et al. Soluble TREM-1 as a predictive factor of neonatal sepsis: a meta-analysis. Inflamm. Res. 67, 571–578 (2018). https://doi.org/10.1007/s00011-018-1149-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-018-1149-4

Keywords

Search

Navigation