Skip to main content

Advertisement

SpringerLink
Log in

Low Levels of Procalcitonin During Episodes of Necrotizing Enterocolitis

  • Original Paper
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The pathogenesis of necrotizing enterocolitis (NEC) remains poorly understood. We aimed to assess the extent of bacterial infection in the pathogenesis of NEC using serial procalcitonin measurements. Blood samples were drawn during the first 4 days following every clinical event requiring a workup for presumed NEC. Eight episodes were confirmed as NEC, 7 of which showed procalcitonin levels <1 ng/ml at presentation and <1.3 ng/ml thereafter, comparable to 24 healthy controls. The one infant with elevated procalcitonin had bacteremia in addition to NEC. Procalcitonin levels of 24 matched septic infants were higher than those of NEC infants, peaking at 4.1 ng/ml. We conclude that low procalcitonin values are the rule during episodes of NEC and provide further evidence that overactive local immune response, and not active infection, is primarily responsible for the mucosal damage in NEC.

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

Similar content being viewed by others

References

  1. Tudehope DI (2005) The epidemiology and pathogenesis of neonatal necrotizing enterocolitis. J Paediatr Child Health 41:167–168

    Article  PubMed  Google Scholar 

  2. Chan KL, Ng SP, Chan KW, Wo YH, Tam PK (2003) Pathogenesis of neonatal necrotizing enterocolitis: a study of the role of intraluminal pressure, age and bacterial concentration. Pediatr Surg Int 19:573–577

    Article  PubMed  CAS  Google Scholar 

  3. Yost CC (2005) Neonatal necrotizing enterocolitis: diagnosis, management, and pathogenesis. J Infus Nurs 28:130–134

    Article  PubMed  Google Scholar 

  4. Luig M, Lui K (2005) Epidemiology of necrotizing enterocolitis. Part II: Risks and susceptibility of premature infants during the surfactant era: a regional study. J Paediatr Child Health 41:174–179

    Article  PubMed  Google Scholar 

  5. Kliegman RM (2005) Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. J Pediatr 146:710

    PubMed  Google Scholar 

  6. Santulli TV, Schullinger JN, Heird WC, Gongaware RD, Wigger J, Barlow B, Blanc WA, Berdon WE (1975) Acute necrotizing enterocolitis in infancy: a review of 64 cases. Pediatrics 55:376–387

    PubMed  CAS  Google Scholar 

  7. Lawrence G, Bates J, Gaul A (1982) Pathogenesis of neonatal necrotising enterocolitis. Lancet 1:137–139

    Article  PubMed  CAS  Google Scholar 

  8. Hsueh W, Caplan MS, Qu XW, Tan XD, De Plaen IG, Gonzalez-Crussi F (2003) Neonatal necrotizing enterocolitis: clinical considerations and pathogenetic concepts. Pediatr Dev Pathol 6:6–23

    Article  PubMed  Google Scholar 

  9. de la Cochetiere MF, Piloquet H, des Robert C, Darmaun D, Galmiche JP, Roze JC (2004) Early intestinal bacterial colonization and necrotizing enterocolitis in premature infants: the putative role of Clostridium. Pediatr Res 56:366–370

    Article  PubMed  Google Scholar 

  10. Hackam DJ, Upperman JS, Grishin A, Ford HR (2005) Disordered enterocyte signaling and intestinal barrier dysfunction in the pathogenesis of necrotizing enterocolitis. Semin Pediatr Surg 14:49–57

    Article  PubMed  Google Scholar 

  11. van Rossum AM, Wulkan RW, Oudesluys-Murphy AM (2004) Procalcitonin as an early marker of infection in neonates and children. Lancet Infect Dis 4:620–630

    Article  PubMed  CAS  Google Scholar 

  12. Pecile P, Miorin E, Romanello C, Falleti E, Valent F, Giacomuzzi F, Tenore A (2004) Procalcitonin: a marker of severity of acute pyelonephritis among children. Pediatrics 114:e249–e254

    Article  PubMed  Google Scholar 

  13. Meisner M SJ, Hüttner H, Tschaikowsky K (2004) The natural elimination rate of procalcitonin in patients with normal and impaired renal function. Intensive Care Med 26:P212–P216

    Article  Google Scholar 

  14. Turner D, Hammerman C, Rudensky B, Schlesinger Y, Schimmel MS (2006) The role of procalcitonin as a predictor of nosocomial sepsis in preterm infants. Acta Paediatr 95(12):1571--1576.

    Google Scholar 

  15. Duffy LC, Zielezny MA, Carrion V, Griffiths E, Dryja D, Hilty M, Rook C, Morin F 3rd (1997) Concordance of bacterial cultures with endotoxin and interleukin-6 in necrotizing enterocolitis. Dig Dis Sci 42:359–365

    Article  PubMed  CAS  Google Scholar 

  16. Harris MC, Costarino AT Jr, Sullivan JS, Dulkerian S, McCawley L, Corcoran L, Butler S, Kilpatrick L (1994) Cytokine elevations in critically ill infants with sepsis and necrotizing enterocolitis. J Pediatr 124:105–111

    Article  PubMed  CAS  Google Scholar 

  17. Grotz MR, Deitch EA, Ding J, Xu D, Huang Q, Regel G (1999) Intestinal cytokine response after gut ischemia: role of gut barrier failure. Ann Surg 229:478–486

    Article  PubMed  CAS  Google Scholar 

  18. Ford H, Watkins S, Reblock K, Rowe M (1997) The role of inflammatory cytokines and nitric oxide in the pathogenesis of necrotizing enterocolitis. J Pediatr Surg 32:275–282

    Article  PubMed  CAS  Google Scholar 

  19. Turner D, Hammerman C, Rudensky B, Schlesinger Y, Goia C, Schimmel MS (2006) Procalcitonin in preterm infants during the first few days of life: introducing an age related nomogram. Arch Dis Child Fetal Neonatal Ed 91:F283–F286

    Article  PubMed  CAS  Google Scholar 

  20. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, Brotherton T (1978) Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 187:1–7

    Article  PubMed  CAS  Google Scholar 

  21. Chiesa C, Panero A, Rossi N, Stegagno M, De Giusti M, Osborn JF, Pacifico L (1998) Reliability of procalcitonin concentrations for the diagnosis of sepsis in critically ill neonates. Clin Infect Dis 26:664–672

    PubMed  CAS  Google Scholar 

  22. Martin CR, Walker WA (2006) Intestinal immune defences and the inflammatory response in necrotising enterocolitis. Semin Fetal Neonatal Med 11:369–377

    Article  PubMed  Google Scholar 

  23. Bury RG, Tudehope D (2001) Enteral antibiotics for preventing necrotizing enterocolitis in low birthweight or preterm infants. Cochrane Database Syst Rev CD000405

  24. Bin-Nun A, Bromiker R, Wilschanski M, Kaplan M, Rudensky B, Caplan M, Hammerman C (2005) Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J Pediatr 147:192–196

    Article  PubMed  Google Scholar 

  25. Lin HC, Su BH, Chen AC, Lin TW, Tsai CH, Yeh TF, Oh W (2005) Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. Pediatrics 115:1–4

    Article  PubMed  Google Scholar 

  26. Ballance WA, Dahms BB, Shenker N, Kliegman RM (1990) Pathology of neonatal necrotizing enterocolitis: a ten-year experience. J Pediatr 117:S6–S13

    Article  PubMed  CAS  Google Scholar 

  27. Sun XM, MacKendrick W, Tien J, Huang W, Caplan MS, Hsueh W (1995) Endogenous bacterial toxins are required for the injurious action of platelet-activating factor in rats. Gastroenterology 109:83–88

    Article  PubMed  CAS  Google Scholar 

  28. Lee JS, Polin RA (2003) Treatment and prevention of necrotizing enterocolitis. Semin Neonatol 8:449–459

    Article  PubMed  Google Scholar 

  29. Claud EC, Walker WA (2001) Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis. FASEB J 15:1398–1403

    Article  PubMed  CAS  Google Scholar 

  30. Israel EJ (1994) Neonatal necrotizing enterocolitis, a disease of the immature intestinal mucosal barrier. Acta Paediatr Suppl 396:27–32

    PubMed  CAS  Google Scholar 

  31. Bush TG (2002) Enteric glial cells. An upstream target for induction of necrotizing enterocolitis and Crohn's disease? Bioessays 24:130–140

    Article  PubMed  Google Scholar 

  32. Habib Z, Arnaud B, Pascal de L, Caroline F, Yves A, Jean-Pierre C, Michel P, Jean-Pierre H, Dominique B (2005) CARD15/NOD2 is not a predisposing factor for necrotizing enterocolitis. Dig Dis Sci 50:1684–1687

    Article  PubMed  Google Scholar 

  33. Szebeni B, Szekeres R, Rusai K, Vannay A, Veres G, Treszl A, Arato A, Tulassay T, Vasarhelyi B (2006) Genetic polymorphisms of CD14, Toll-like receptor 4, and caspase-recruitment domain 15 are not associated with necrotizing enterocolitis in very low birth weight infants. J Pediatr Gastroenterol Nutr 42:27–31

    Article  PubMed  CAS  Google Scholar 

  34. Neu J, Chen M, Beierle E (2005) Intestinal innate immunity: How does it relate to the pathogenesis of necrotizing enterocolitis. Semin Pediatr Surg 14:137–144

    Article  PubMed  Google Scholar 

  35. Warner BW, Warner BB (2005) Role of epidermal growth factor in the pathogenesis of neonatal necrotizing enterocolitis. Semin Pediatr Surg 14:175–180

    Article  PubMed  Google Scholar 

  36. Caplan MS, MacKendrick W (1994) Inflammatory mediators and intestinal injury. Clin Perinatol 21:235–246

    PubMed  CAS  Google Scholar 

  37. Caplan MS, Sun XM, Hseuh W, Hageman JR (1990) Role of platelet activating factor and tumor necrosis factor-alpha in neonatal necrotizing enterocolitis. J Pediatr 116:960–964

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

BRAHMS Diagnostica provided the testing kits for PCT determination but was not involved in any part of the study design, data collection, data analysis, or manuscript preparation. The authors wish to thank the nurses of NICU who meticulously collected the blood samples.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Shaare Zedek Medical Center, Jerusalem, Israel

    Dan Turner

  2. Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel

    Cathy Hammerman & Michael S. Schimmel

  3. Clinical Microbiology Laboratory Shaare Zedek Medical Center, Jerusalem, Israel

    Bernard Rudensky

  4. Pediatric Infectious Disease Unit, Shaare Zedek Medical Center, Jerusalem, Israel

    Yechiel Schlesinger

  5. Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G-1X8, Canada

    Dan Turner, Eytan Wine & Aleixo Muise

Authors
  1. Dan Turner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cathy Hammerman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernard Rudensky
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yechiel Schlesinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eytan Wine
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aleixo Muise
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michael S. Schimmel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dan Turner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Turner, D., Hammerman, C., Rudensky, B. et al. Low Levels of Procalcitonin During Episodes of Necrotizing Enterocolitis. Dig Dis Sci 52, 2972–2976 (2007). https://doi.org/10.1007/s10620-007-9763-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-007-9763-y

Keywords

Search

Navigation