The Cut-off Point of Ferritin, Procalcitonin, and Serum CRP Levels in the Peripheral Blood of Neonates Suffering from Sepsis

Document Type: Original Article

Authors

1 Assistant Professor, Clinical Research Development Unit, Ali-Ibn Abi-Talib Hospital, & Social Medicine Department, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

2 General physician, Clinical Research Development Unit, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

3 Professor, Molecular Medicine Research Centre, Institute of Basics Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

4 Assistant Professor, Non-communicable Diseases Research Center, & Clinical Research Development Unit, Ali-Ibn Abi-Talib Hospital, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

5 Assistant Professor, Neonates Department, Ali-Ibn Abi-Talib Hospital, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

Abstract

Background: Sepsis is regarded as a critical clinical status in neonates. Since blood culture is a time-consuming method, the present study was conducted to investigate the serum level of Ferritin, Procalcitonin, and CRP in the peripheral blood of term neonates suspected with sepsis to have a quicker diagnosis for the disease.
Methods: In the present cross-sectional study, a total of 60 neonates suspected with sepsis who had been hospitalized in Ali ibn Abi Talib Hospital of Rafsanjan/ Iran in 2015-2016 were randomly selected. Before conducting the treatment processes, blood samples were taken from all neonates and sent for blood culture. The intended markers were measured both before and after the treatments and the results were recorded in special forms for each neonate. Data were analyzed through SPSS20 and using chi-squared test, Paired t-test, and drawing a ROC curve for determining the best cut-off point and measuring the sensitivity and specificity.
Results: In this study, 70% of the neonates suspected with sepsis were male, 56.7% were younger than 7 days old and 96.7% had natural weight. The most common symptoms were poor feeding and reduced sucking reflexes. Data analysis of the markers indicate that they reduced significantly after the treatment (p<0.001). The sensitivity, specificity, and the best cut-off point were respectively 64.3%, 43.5%, and 257.8 for Ferritin, 78.6%, 50%, and 23 for Procalcitonin and 85.7%, 65.2%, and 21.5 for CRP.
Conclusion: According to the obtained findings, applying these markers can be of a great use in diagnosing neonatal sepsis. However, given the low sensitivity and specificity of Ferritin, Procalcitonin and CRP in the present study, further studies need to be conducted to obtain more definite results.

Keywords


  1. Wynn JL. Defining neonatal sepsis. Curr Opin Pediatr 2016; 28(2):135-40.
  2. Obiero CW, Seale AC, Berkley JA. Empiric treatment of neonatal sepsis in developing countries. Pediatr Infect Dis J 2015; 34(6):659-61.
  3. Kale A, jaybhaye D, Bonde V. Neonatal Sepsis: An Update. Iranian Journal of Neonatology 2014; 4(4): 39-51.
  4. Zea-Vera A, Turin CG, Ochoa TJ. Unifying criteria for late neonatal sepsis: proposal for an algorithm of diagnostic surveillance. Rev Peru Med Exp Salud Pública 2014; 31(2):358-63. [In Spanish]..
  5. Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am 2013; 60:367-89.
  6. Oeser C, Lutsar I, Metsvaht T, Turner MA, Heath PT, Sharland M. Clinical trials in neonatal sepsis. J Antimicrob Chemother 2013; 68(12):2733-45.
  7. Bedford Russell AR, Kumar R. Early onset neonatal sepsis: diagnostic dilemmas and practical management. Arch Dis Child Fetal Neonatal Ed 2015; 100(4):F350-4.
  8. Saleh MA, Kasem YT, Amin HH. Evaluation of neonatal sepsis and assessment of its severity by red cell distribution width indicator. The Egyptian Journal of Community Medicine 2017; 35(3):21-32.
  9. Tröger B, Göpel W, Faust K, Müller T, Jorch G, Felderhoff-Müser U, et al. Risk for late-onset blood-culture proven sepsis in very-low-birth weight infants born small for gestational age: a large multicenter study from the German Neonatal Network. Pediatr Infect Dis J 2014; 33(3):238-43.
  10. Gokmen Z, Ozkiraz S, Kulaksizoglu S, Kilicdag H, Ozel D, et al. Resistin-a novel feature in the diagnosis of sepsis in premature neonates. Am J Perinatol 2013; 30(6):513-7.
  11. Kibe S, Adams K, Barlow G. Diagnostic and prognostic biomarkers of sepsis in critical care. J Antimicrob Chemother 2011; 66(suppl-2):ii33-40.
  12. Gibot S, Béné MC, Noel R, Massin F, Guy J, Cravoisy A, et al. Combination biomarkers to diagnose sepsis in the critically ill patient. Am J Respir Crit Care Med 2012; 186(1):65-71.
  13. Wu J, Hu L, Zhang G, Wu F, He T. Accuracy of presepsin in sepsis diagnosis: a systematic review and meta-analysis. PLoS One 2015; 10(7):e0133057.
  14. Hedegaard SS, Wisborg K, Hvas AM. Diagnostic utility of biomarkers for neonatal sepsis–a systematic review. Infect Dis (Lond) 2015; 47(3):117-24.
  15. Patra S. Procalcitonin in neonatal sepsis. Int J Sci Res. 2018; 6(3).
  16. Kalil AC, Van Schooneveld TC. Is procalcitonin-guided therapy associated with beneficial outcomes in critically ill patients with sepsis? Critic Care Med 2018; 46(5):811-2.
  17. Schlattmann P, Brunkhorst FM. Procalcitonin as a diagnostic marker for sepsis. Lancet Infect Dis 2014; 14(3):189.
  18. Chivate CG, Belwalkar GJ, Limaye RP, Patil RV. Procalcitonin as a marker for the diagnosis of sepsis. Int J Res Med Sci 2016; 4(4):1216-8.
  19. Prucha M, Bellingan G, Zazula R. Sepsis biomarkers. Clin Chimica Acta 2015; 440:97-103.
  20. Cho SY, Choi JH. Biomarkers of sepsis. Infect Chemother 2014; 46(1):1-2.
  21. Branco RG, Garcia PC. Ferritin and C-reactive protein as markers of systemic inflammation in sepsis. Pediatr Critic Care Med 2017; 18(2):194-6.
  22. Garcia PC, Longhi F, Branco RG, Piva JP, Lacks D, Tasker RC. Ferritin levels in children with severe sepsis and septic shock. Acta Paediatr 2007; 96(12):1829-31.
  23. Halstead ES, Rajasekaran S, Fitzgerald JC, Weiss SL. Hyperferritinemic sepsis: an opportunity for earlier diagnosis and intervention? Front Pediatr 2016; 4:77.
  24. Kanda J, Mizumoto C, Ichinohe T, Kawabata H, Saito T, Yamashita K, et al. Pretransplant serum ferritin and C-reactive protein as predictive factors for early bacterial infection after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 2011; 46(2):208-16.
  25. Demirkol D, Yildizdas D, Bayrakci B, Karapinar B, Kendirli T, Koroglu TF, et al. Hyperferritinemia in the critically ill child with secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ dysfunction syndrome/macrophage activation syndrome: what is the treatment? Critic Care 2012; 16(2):R52.
  26. Arif SK, Suyata MP, Gaus S, Ahmad MR. Procalcitonin and C-reactive protein as a predictor of organ dysfunction and outcome of sepsis and septic shock patients in intensive care unit. Glob J Health Sci 2017; 9(12):169.
  27. Abdollahi E, Farshi S, Hajian Motlaq N, Abdollahi S. Patient satisfaction in the emergency department of Savodjbolaq hospitals. Alborz University Medical Journal 2015; 4(3):176-83. [In Persian].
  28. Celik HT, Portakal O, Yigit S, Hascelik G, Korkmaz A, Yurdakok 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(2):119-25.
  29. Aydemir C, Aydemir H, Kokturk F, Kulah C, Mungan AG. The cut-off levels of procalcitonin and C-reactive protein and the kinetics of mean platelet volume in preterm neonates with sepsis. BMC Pediatr 2018; 18(1):253.
  30. Farhadi K, Ghaemipour F, Nikravan M, Alavi Majd H. The study of the quality of triage of the patients admitted to intensive care unit. Iranian Journal of Cardiovascular Nursing 2013; 2(1):12-6. [In Persian].
  31. Charles E, Nolan I, Hickey A, Greenough A, Kassim Z. C-reactive protein in otherwise well babies with risk factors for sepsis. Infant journal 2017; 13(4):154-5.
  32. Van Herk W, El Helou S, Janota J, Hagmann C, Klingenberg C, Staub E, et al. Variation in current management of term and late-preterm neonates at risk for early-onset sepsis: an international survey and review of guidelines. Pediatr Infect Dis J 2016; 35(5):494-500.
  33. Simonsen KA, Anderson-Berry AL, Delair SF, Davies HD. Early-onset neonatal sepsis. Clin Microbiol Rev 2014; 27(1):21-47.
  34. Ng PC, Ma TP, Lam HS. The use of laboratory biomarkers for surveillance, diagnosis and prediction of clinical outcomes in neonatal sepsis and necrotising enterocolitis. Archives of Disease in Childhood-Fetal and Neonatal Edition 2015; 100(5):F448-52.
  35. Benitz WE, Wynn JL, Polin RA. Reappraisal of guidelines for management of neonates with suspected early-onset sepsis. J Pediatr 2015; 166(4):1070-4.
  36. Pontrelli G, De Crescenzo F, Buzzetti R, Jenkner A, Balduzzi S, Carducci FC, et al. Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and children with systemic inflammatory syndrome: a meta-analysis. BMC Infect Dis 2017; 17(1):302.
  37. Abedini M, Delpisheh A, Nikkhu B, Vahabi A, Afkhamzadeh A. Procalcitonin and white blood cellcount (WBC),erythrocyte sedimentation rate(ESR) and serumC-reactive protein(CRP)alterations in children with systemic inflammatory response syndrome before and after treatment. African Journal of Biotechnology 2012; 11(49):10989-93.
  38. Benitz WE. Adjunct laboratory tests in the diagnosis of early-onset neonatal sepsis. Clin Perinatol 2010; 37(2):421-38.
  39. Casado-Flores J, Blanco-Quirós A, Asensio J, Arranz E, Garrote JA, Nieto M. Serum procalcitonin in children with suspected sepsis: a comparison with C-reactive protein and neutrophil count. Pediatr Crit Care Med 2003; 4(2):190-5.
  40. Jalali SZ, Heidarzadeh A, Khatti Dizabadi B. Diagnostic value of procalcitonin for sepsis diagnosis in ill neonate hospitalized in neonatal ward and NICU. Journal of Guilan University of Medical Sciences 2014; 22(88):12-7. [In Persian].
  41. Ayub A, Chishti AL, Hassen KA. The validity of hematologic markers for diagnosis of neonatal sepsis. Annals of King Edward Medical University 2015; 21(4):240-6.
  42. Jin M, Khan AI. Procalcitonin: uses in the clinical laboratory for the diagnosis of sepsis. Lab Med 2015; 41(3):173-7.
  43. Wynn JL, Guthrie SO, Wong HR, Lahni P, Ungaro R, Lopez MC, et al. Postnatal age is a critical determinant of the neonatal host response to sepsis. Mol Med 2015; 21:496-504.