Can Endocan Predict Late-Onset Neonatal Sepsis?Funding None.
25 April 2018
14 September 2018
24 October 2018 (eFirst)
Objective Endocan, a proteoglycan secreted by endothelial cells, plays a role in the pathogenesis of sepsis. Endocan is an effective diagnostic and prognostic biomarker of sepsis in adult patients. We evaluate the utility of endocan as a new biomarker in the recognition of late-onset neonatal sepsis (LOS) in preterm infants.
Methods This study included preterm infants at gestational age ≤ 32 weeks diagnosed with LOS. Sepsis was diagnosed in the presence of three or more clinical findings plus significant elevation of C-reactive protein (CRP) or interleukin 6 (IL-6) levels. Blood samples were obtained to determine leukocyte count, CRP, IL-6, and endocan levels immediately after the sepsis diagnosis and on the 3rd and 7th day after diagnosis.
Results A total of 102 preterm infants, 52 with LOS (21 proven, 31 suspected sepsis) and 50 controls, were included in the study. Mean leukocyte count, serum CRP, IL-6, and endocan levels were significantly higher in the LOS group compared with healthy controls (p < 0.001) at enrolment. Serial measurements showed no significant difference in CRP and IL-6 levels between the proven and suspected sepsis groups, while endocan levels were significantly higher at enrolment and on day 7 in the proven sepsis group (p = 0.003 and p = 0.01, respectively). The endocan levels of preterm infants who died were significantly higher at all time points (p < 0.001, p = 0.001, and p = 0.004, respectively).
Conclusion Endocan is an effective, reliable, and promising new biomarker for detecting LOS in preterm infants.
M. Buyuktiryaki, C. Tayman, M.Y. Oncel, and S.S. Oguz designed the research; M. Buyuktiryaki, N. Okur, U. Cakır, and H. Halil undertook data collection; U. Serkant performed the data analysis and interpretation; M. Buyuktiryaki, C. Tayman, and M.Y. Oncel performed the statistical analyses; M. Buyuktiryaki, N. Okur, U. Cakır, H. Halil, C. Tayman, and S.S. Oguz wrote the paper. M. Buyuktiryaki and C. Tayman had primary responsibility for the final content.
- 1 Isaacs D. Australasian Study Group For Neonatal Infections. A ten year, multicentre study of coagulase negative staphylococcal infections in Australasian neonatal units. Arch Dis Child Fetal Neonatal Ed 2003; 88 (02) F89-F93
- 2 Stoll BJ, Hansen N, Fanaroff AA. , et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002; 110 (2 Pt 1): 285-291
- 3 Härtel C, Faust K, Avenarius S. , et al; German Neonatal Network (GNN) Epidemic microclusters of blood-culture proven sepsis in very-low-birth weight infants: experience of the German Neonatal Network. PLoS One 2012; 7 (06) e38304
- 4 Hornik CP, Fort P, Clark RH. , et al. Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. Early Hum Dev 2012; 88 (88, Suppl 2): S69-S74
- 5 Hedegaard SS, Wisborg K, Hvas AM. Diagnostic utility of biomarkers for neonatal sepsis--a systematic review. Infect Dis (Lond) 2015; 47 (03) 117-124
- 6 Gerdes JS. Diagnosis and management of bacterial infections in the neonate. Pediatr Clin North Am 2004; 51 (04) 939-959 , viii–ix
- 7 Khassawneh M, Hayajneh WA, Kofahi H, Khader Y, Amarin Z, Daoud A. Diagnostic markers for neonatal sepsis: comparing C-reactive protein, interleukin-6 and immunoglobulin M. Scand J Immunol 2007; 65 (02) 171-175
- 8 Kao PC, Shiesh SC, Wu TJ. Serum C-reactive protein as a marker for wellness assessment. Ann Clin Lab Sci 2006; 36 (02) 163-169
- 9 Buck C, Bundschu J, Gallati H, Bartmann P, Pohlandt F. Interleukin-6: a sensitive parameter for the early diagnosis of neonatal bacterial infection. Pediatrics 1994; 93 (01) 54-58
- 10 Aird WC. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 2003; 101 (10) 3765-3777
- 11 Kali A, Shetty KS. Endocan: a novel circulating proteoglycan. Indian J Pharmacol 2014; 46 (06) 579-583
- 12 Bechard D, Meignin V, Scherpereel A. , et al. Characterization of the secreted form of endothelial-cell-specific molecule 1 by specific monoclonal antibodies. J Vasc Res 2000; 37 (05) 417-425
- 13 Chang X, Bian Y, Wu Y, Huang Y, Wang K, Duan T. Endocan of the maternal placenta tissue is increased in pre-eclampsia. Int J Clin Exp Pathol 2015; 8 (11) 14733-14740
- 14 Béchard D, Scherpereel A, Hammad H. , et al. Human endothelial-cell specific molecule-1 binds directly to the integrin CD11a/CD18 (LFA-1) and blocks binding to intercellular adhesion molecule-1. J Immunol 2001; 167 (06) 3099-3106
- 15 Scherpereel A, Depontieu F, Grigoriu B. , et al. Endocan, a new endothelial marker in human sepsis. Crit Care Med 2006; 34 (02) 532-537
- 16 Mihajlovic DM, Lendak DF, Brkic SV. , et al. Endocan is useful biomarker of survival and severity in sepsis. Microvasc Res 2014; 93: 92-97
- 17 Seo K, Kitazawa T, Yoshino Y, Koga I, Ota Y. Characteristics of serum endocan levels in infection. PLoS One 2015; 10 (04) e0123358
- 18 Saldir M, Tunc T, Cekmez F. , et al. Endocan and soluble triggering receptor expressed on myeloid cells-1 as novel markers for neonatal sepsis. Pediatr Neonatol 2015; 56 (06) 415-421
- 19 Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis. Lancet 2017; 390 (10104): 1770-1780
- 20 Gitto E, Karbownik M, Reiter RJ. , et al. Effects of melatonin treatment in septic newborns. Pediatr Res 2001; 50 (06) 756-760
- 21 Haque KN. Definitions of bloodstream infection in the newborn. Pediatr Crit Care Med 2005; 6 (3, Suppl): S45-S49
- 22 Gonzalez BE, Mercado CK, Johnson L, Brodsky NL, Bhandari V. Early markers of late-onset sepsis in premature neonates: clinical, hematological and cytokine profile. J Perinat Med 2003; 31 (01) 60-68
- 23 Celik IH, Demirel FG, Uras N. , et al. What are the cut-off levels for IL-6 and CRP in neonatal sepsis?. J Clin Lab Anal 2010; 24 (06) 407-412
- 24 Çelik HT, Portakal O, Yiğit Ş, Hasçelik G, Korkmaz A, Yurdakök M. Efficacy of new leukocyte parameters versus serum C-reactive protein, procalcitonin, and interleukin-6 in the diagnosis of neonatal sepsis. Pediatr Int 2016; 58 (02) 119-125
- 25 Ng PC. Diagnostic markers of infection in neonates. Arch Dis Child Fetal Neonatal Ed 2004; 89 (03) F229-F235
- 26 Bhandari V. Effective biomarkers for diagnosis of neonatal sepsis. J Pediatric Infect Dis Soc 2014; 3 (03) 234-245
- 27 Chauhan N, Tiwari S, Jain U. Potential biomarkers for effective screening of neonatal sepsis infections: an overview. Microb Pathog 2017; 107: 234-242
- 28 Sharma D, Farahbakhsh N, Shastri S, Sharma P. Biomarkers for diagnosis of neonatal sepsis: a literature review. J Matern Fetal Neonatal Med 2018; 31 (12) 1646-1659
- 29 Ng PC, Lam HS. Biomarkers for late-onset neonatal sepsis: cytokines and beyond. Clin Perinatol 2010; 37 (03) 599-610
- 30 Delanghe JR, Speeckaert MM. Translational research and biomarkers in neonatal sepsis. Clin Chim Acta 2015; 451 (Pt A) 46-64
- 31 De Freitas Caires N, Legendre B, Parmentier E. , et al. Identification of a 14 kDa endocan fragment generated by cathepsin G, a novel circulating biomarker in patients with sepsis. J Pharm Biomed Anal 2013; 78-79: 45-51
- 32 Pauly D, Hamed S, Behnes M. , et al. Endothelial cell-specific molecule-1/endocan: diagnostic and prognostic value in patients suffering from severe sepsis and septic shock. J Crit Care 2016; 31 (01) 68-75
- 33 Halil H, Tayman C, Cakır U, Buyuktiryaki M, Serkant U, Oğuz SS. Serum endocan level as a predictive marker for hemodynamically significant patent ductus arteriosus in very low birth weight infants. Am J Perinatol 2017; 34 (13) 1312-1317
- 34 Kechagia M, Papassotiriou I, Gourgoulianis KI. Endocan and the respiratory system: a review. Int J Chron Obstruct Pulmon Dis 2016; 11: 3179-3187