Hematological and Biological Markers of Neonatal Sepsis

Document Type: Review Article

Authors

1 Dept. of Pathology, Regional Institute of Medical Sciences, Imphal, India

2 Dept. of Microbiology, Regional Institute of Medical Sciences, Imphal, India

Abstract

 
Septicemia in neonates is the commonest cause of mortality. Early recognition and diagnosis of neonatal sepsis remains a challenge because of the variable and nonspecific clinical presentation. The laboratory criteria are often non specific and not fully reliable. The objective of this review is to highlight the various hematological and biological markers of neonatal sepsis. We searched PubMed and Elsevier’s web of science from studies evaluating the hematological and biological markers of neonatal sepsis. The key words used were “neonatal sepsis”, “hematological marker” and ”biomarker”. Since a battery of markers of neonatal sepsis are available, it is always better to rely on a combination of markers along with the clinical correlation.
 

Keywords


  1. Chirico G, Cortinovis S, Fonte C, Gindici G. Bacterial sepsis. J Chemother 2007; 19: 28-30.
  2. Chirico G. Development of the immune system in neonates. J Arab Neonatal Forum 2005; 2: 5-11.
  3. Stichm ER, Ochs HD, Winkelstein JA. Immunologic disorders in infants and children. 5th ed. Philadelphia:Elsevier Saunders Company;2004.
  4. Modi N, Carr R. Promising stratagens for reducing the burden of neonatal sepsis. Arch Dis Child Fetal Neonatal Ed 2000; 83 (2):F150-3.
  5. Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, et al. Late onset sepsis in very low birth weight neonates: the experience of the NICHD neonatal Research Network. Paediatrics 2002; 110: 285-91.
  6. Lawn JE, Wilczynska-Ketende K, Cousens SN. Estimating the cause of four million neonatal deaths in the year 2000. Int J Epidemiol 2006; 35 (3): 706-18.
  7. Jaswal RS, Kaushal RK, Goel A, Pathania K. Role of the C-reactive protein in deciding the duration of the antibiotic therapy in neonatal septicaemia. Indian Pediatr 2003; 40(9): 880-3.
  8. Remington JS, Klein JO, Wilson CB, Baker CJ. Infectious diseases of fetuses and newborn infants. N Engl J Med 2006; 355: 531-2.
  9. Panero A, Pacifico L, Rossi N, Mancuso G, Stegagno M, Chelsa C. Interleukin 6 in neonates with early and late onset infections. Pediatr Infect Dis J 1997; 16 (4): 370-5.
  10. Haque KN. Neonatal sepsis in the very low birth weight preterm infants: Part 2: Review of definition, diagnosis and management. J Med Sci 2010; 3(1): 11-27.
  11. Chirico G, Loda C. Laboratory aid to the diagnosis and therapy of infection in the neonate. Paediatric Reports 2011; 3: e1.doi: 10.4081/pr.2011.e1.
  12. Tripathi S, Malik GK. Neonatal sepsis: past, present and future: a review article. Internet J Med Update 2010; 5(2): 45-54.
  13. Singhal T. Blood cultures revisited. Pediatr Infect Dis J 2012; 4(1): 25-7.
  14. Schelonka RL, Chai MK, Yoder BA, Hensley D, Brockett R M, Ascher D P. Volume of blood required to detect common neonatal pathogens. J Pediatr 1996; 129 (2): 275-8.
  15. Ng PC, Cheng SH, Chiu KM, Fok TF, Wong MY, Wong W, et al. Diagnosis of late onset neonatal sepsis with cytokines, adhesion molecules and C-reactive protein in preterm very low birthweight infants. Arch Dis Child Fatal Neonatal Ed 1997; 77(3): F221-7.
  16. Ng PC, Li K, Wong RP, Chui KM, Wong E, Fok TF. Neutrophil CD64 expression: a sensitive diagnostic marker for late onset nocosomial infection in very low birth weight infants. Paediatr Res 2002; 51 (3): 296-303.
  17. Berger C, Uehlinger J, Ghelfi D, Blau N, Fanconi Sl. Comparison of C-reactive protein and white blood cell count with diferential in neonates at risk of septicaemia. Eur J Pediatr 1995; 154(2): 138-44.
  18. Da Silva O, Ohlsson A, Kenyan C. Accuracy of leukocyte indices and C-reactive protein for diagnosis of neonatal sepsis: a critical review. Pediatr Infect Dis J 1995; 14(5): 362-6.
  19. Rodwell RL, Leslie AL, Tudehope DI. Early diagnosis of neonatal sepsis using a haematological scoring system. J Pediatr 1988; 112: 761-7.
  20. Howard MR, Smith RA. Early diagnosis of septicaemia in preterm infants from examination of peripheral blood films. Clin Lab Haematol 1999; 21(5): 365-8.
  21. Baltimore RS. Neonatal sepsis: epidemiology and management. Paediatr Drugs 2003;5(11): 723-40.
  22. Manroe BL, Weinberg AG, Rosenfeld CR, Browne R. The neonatal blood count in health and disease (1): reference values for neutrophilic cells. J Pediatr 1979; 95(1): 89-98.
  23. Seibert K, Yu VY, Doery JC, Embury D. The value of C-reactive protein measurement in the diagnosis of neonatal infection. J Pediatr Child Health 1990; 26(5): 267-70.
  24. Hatherill M, Tibby SM, Sykes K, Turner C, Murdoch IA. Diagnostic markers of infection: comparision of procalcitonin with C-reactive protein and leukocyte count. Arch Dis Child 1999;81(5):417-21.
  25. Chirico G, Gasparoni A, Ciardelli L, Martinotti L, Rondini G. Leukocyte counts in relation to the method of delivery during the first five days of life. Biol Neonate 1999;75(5):294-9.
  26. Narasimha A, Kumar MLH. Singnificance of haematological scoring system in early diagnosis of neonatal sepsis. Indian J Hematol Blood Transfus 2011; 27(1):14-7.
  27. Kabir KB, Rahman MA, Sultana T, Roy CK, Rahman MQ, Ahmed AN. Early diagnosis of neonatal septicaemia by hematologic scoring system, C-reactive protein and serum haptaglobin. Mymensingh Med J 2012;21(1):85-92.
  28. Ghosh S, Mittal M, Jaganathan G. Early diagnosis of neonatal sepsis using a hematological scoring system. Indian J Med Sci 2001;55:495-500.
  29. Remington JS, Klein JO. Infectious diseases of the fetus and newborn infants. 6thed. Philadelphia: W.B.Saunders company; 2006.
  30. Kennon C, Overturf G, Bessman S, Sierra E, Smith KJ, Brann B. Granulocytic colony stimulating factor as a marker for bacterial infection in neonates. J Pediatr 1996;128(6):765-9.
  31. Gessler P, Kirchmann N, Kientsch-Engel R, Haas N, Lasch P, Kachel W. Serum concentrations of granulocyte colony stimulating factor in healthy term and preterm neonates and in those with various diseases including bacterial infections. Blood 1993;82(10):3177-82.
  32. Mautone A, Giordano P, Montagna O, Quercia M, Altomare M, De Mattia D. Coagulation and fibrinolytic systems in the ill preterm newborn. Acta Paediatr 1997;86(10):1100-4.
  33. Raaphorrt J, Johan-Groeneveld AB, Bossink AW, Erik Hack C. Early inhibition of activated fibrinolysis predicts microbial infection, shock and mortality in febrile medical patients. Thrombosis Haemostasis 2001;86(2):543-9.
  34. Guibourdenche J, Bedu A, Petzold L, Marchand M, Mariani-Kurdjian P,Hurtaud-Roux MF, et al. Biochemical markers of neonatal sepsis: value of procalcitonin in the emergency setting. Ann Clin Biochem 2002;39(Pt 2):130-5.
  35. Vigushin D, Pepys M, Hawkins P. Metabolic and scintigraphic studies of radio iodinated human C-reactive protein in health and disease. J Clin Invest 1993;91: 1351-7.
  36. Pourcyrous M, Bada HS, Korones SB, Baselski V, Wong SP. Singnificance of serial C-reactive protein responses in neonatal infection and other disorders. Pediatrics 1993;92(3):431-5.
  37. Carrol CD, Thomson AP. Procalcitonin as a marker of sepsis. Int J Antimicrob Agents 2002;20(1):1-9.
  38. Gendrel D, Bohoun C. Procalcitonin as a marker of bacterial infection. Pediatr Infect Dis J 2002;19(8):679-87.
  39. Dandona P, Nix D, Wilson MF, Aljada A, Love J, Assicot M, et al. Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab 1994;79(6):1605-8.
  40. Chiesa C, Panero A. Rossi N, Stegagno M, De giusti M, Osborn JE,et al. Reliability of procalcitonin concentration for the diagnosis of sepsis in critically ill neonates. Clin Infect Dis1998;26(3):664-72.
  41. Gendrel D, Assicot M, Raymond J, Moulin F, Framcoual C, Badoual J, et al. Procalcitonin as a marker for the early diagnosis of neonatal infection. J Pediatr 1996;128(4):570-3.
  42. Nnanna II, Ehis OJ, Sidiquo II, Nnanna IG, Adekunle O. Serum procalcitonin: Early detection of neonatal bacteremia and septicaemia in a tertiary health care facility. North Am J Med Sci 2011;3:157-60.
  43. Adib M, Bakhshiani Z, Navaei F, Fosoul FS, Fouladi S, Kazemzadeh H. Procalcitonin: a reliable marker for the diagnosis of neonatal sepsis. Iran J Basic Sci 2012;15(1):777-82.
  44. Sucilathangam G, Amuthavalli K, Velvizhi G, Ashihabegum MA, Jeyamurugan T, Palaniappan N. Early diagnostic marker for neonatal sepsis: comparing procalcitonin and C-reactive protein. J Clin Diag Res 2012;Suppl-2; 6(4)627-31.
  45. Cesur S. Neopterin: a marker used for monitoring infections. Mikryobiyol Bul 2005;39(2):251-60.
  46. Boseila S, Seoud I, Samy G, El-Gamal H, Ibrahim TS, Ahmed A, et al. Serum neopterin level in early onset neonatal sepsis. J Am Sci 2011;7(7):343-52.
  47. Spur Ch, Burns A, Gahr M. Sequential determination of CRP, α1-antitrypsin and haptaglobin in neonatal septicaemia. Acta Paediatr Scand 1983;72:679-83.
  48. Gerdes JS, PAlin RA. Sepsis screen in neonates with evaluation of plasma fibronectin. Pediatr Infect Dis J 1987;6:443-6.
  49. Scott PH. Plasma lactoferrin levels in newborn preterm infants: effect of infection. Am Clin Biochem 1989;26:412-5.
  50. Meisner M. Biomarkers of sepsis: clinically useful? Curr Opin Crit Care 2005;11: 473-80.
  51. Schultz C, Rott C, Temming P, Schlenke P, Moller JC, Bucsky P. Enhanced interleukin-6 and interleukin-8 synthesis in term and preterm infants. Pediatr Res 2002;51(3):317-22.
  52. Tasci Y, Dilbaz B, Uzmez Onal B, Caliskan E, Dilbaz S, Doganei L, et al. The value of cord blood interleukin-6 levels for predicting chorioamnionitis, funisitis and neonatal infection in term premature rupture of membranes. Eur J Obstet Gynecol Reprod Biol 2006;128:34-9.
  53. Messer J, Eyer D, Donato L , Gallati H, Matis J, Simeoni U. Evaluation of interleukin-6 soluble receptors of tumor necrosis factor for early diagnosis of neonatal infection. J Pediatr 1996;129(4):574-80.
  54. Smulian JC, Vintzileos AM, Lai YL, Santiago J, Shen-Schwarz S, Campbell WA. Maternal Chorioamnionitis and umbilical vein interleukin-6 levels for identifying early neonatal sepsis. J Matern Fetal Med 1999;8(3):88-94.
  55. Fan Y, Yu J. Umbilical blood biomarkers for predicting early onset neonatal sepsis. World J Pediatr 2012;8(2):101-8.
  56. Franz AR, Steinbach G, Kron M, Pohlandt F. Reduction of unnecessary antibiotic therapy in newborn infants using IL-8 and CRP as markers of bacterial infections. Pediatrics 1999;104:447-53.
  57. Berner R, Tuxen B, Clad A, Forster J, Brandis M. Elevated gene expression of interleukin-8 in cord blood is a sensitive marker for neonatal infection. Eur J Pediatr 2000;159(3):205-10.
  58. Blanco A, Solis G, Arranz E, Coto GD, Ramos A, Telleria J. Serum levels of CD14 in neonatal sepsis with gram positive and gram negative bacteria. Acta Pediatr 1996;85:728-32.
  59. Weirich E, Rabin RL, Maldonado Y, Benitz W, Modler S, Herzenberg LA, et al. Neutrophil CD 116 expression as a diagnostic marker for early onset neonatal infection. J Pediatr 1998;132(3):445-51.
  60. Lai Y, Wang C, Hua Y, Hung C. Expression of neutrophil CD11b in preterm neonate and neonatal sepsis: a preliminary report. J Med Sci 2005;25(4):181- 4.
  61. Genel F, Attihan F, Gulez N, Kazanci E, Verin C, Terek DT, et al. Evaluation of adhesion molecules CD64, CD11b and CD62L in neutrophils and monocytes of peripheral blood for early diagnosis of neonatal infection. World J Pediatr 2012; 8(1):72-5.
  62. Streimish I, Bizzarro M, Northrup V, Wang C, Renna S, Koval N, et al. Neutrophil CD64 as a diagnostic marker in neonatal sepsis. Pediatr Infect Dis J 2012;31(7): 777-81.
  63. Weinschenk NP, Farina A, Bianchi DW. Premature infants respond to early onset and late onset sepsis with leukocyte activation. J Pediatr 2000;137:345-50.
  64. Mishra UK, Jacobs SE, Doyle LW, Garland SM. Newer approaches to the diagnosis of early onset neonatal sepsis. Arch Dis Child Fetal Neonatal Ed 2006; 91:F208-12.
  65. Rittichier KR, BryanPA,Bassett KE, Taggart EW, Enriquez FR, Hillyard DR, et al. Diagnosis and outcomes of enterovirus infections in young infants. Pediatr Infect Dis J 2005;24:546-50.
  66. Heim A, Ebnet G, Pring-Akerblom P. Rapid and quantitative detection of human adenovirus DNA by real time PCR. J Med Virol 2003;70:228-39.
  67. Golden SM, Stamilio DM, Faux BM, dela Cruz WP, Shoemaker CT, Black-mon CL, et al. Evaluation of a real time fluorescent PCR assay for rapid detection of Group B streptococci in neonatal blood. Diag Microbiol Infect Dis 2004;50:7-13.
  68. Ng PC, Li K, Chui KM, Leung TF, Wong RPO, Chu WCW, et al. IP-10 is a early diagnostic marker for identification of late onset bacterial infection in preterm infants. Pediatr Res 2007;61:93-8.
  69. Yui S, Nakatani Y, Mikami M. Calprotectin (S 100A8/ S100A9), an inflammatory protein complex from neutrophils with a broad apoptosis inducing activity. Biol Pharm Bull 2003; 26(6):753-60.
  70. Maaboud MA, El-Mazary AM, Osman AM. Serum calprotectin as a diagnostic marker of late onset sepsis in full term neonats. Egypt J Pediatr Allergy Immunol 2012;10(1):19-24.
  71. Terrin G, Passariello A, Manquso F, Salvia G, Rapacciuolol, Messina F, et al. Serum calprotectin: an antimicrobial peptide as a new marker for the diagnosis of sepsis in very low birth weight newborns. Clin Dev Immunol 2011;2011:291085.
  72. Shozushima T. Presepsis (sCD14-ST) as a new diagnostic biomarker of sepsis: development of diagnostic tools using the whole blood. Critical Care 2010, 15 (suppl-3): P3 (doi: 10.1186/CC10372)
  73. Buhimschi CS, Bhandari V, Han YW, Dulay AT, Baumbusch MA, Madri JA, et al. Using proteomics in perinatal and neonatal sepsis: hopes and challenges for the future. Curr Opin Infect Dis 2009;22(3):235-43.