Fecal Calprotectin Level in Neonates with Necrotizing Enterocolitis

Document Type : Original Article


Pediatrics Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt


Background: Necrotizing enterocolitis (NEC) is a disease with high mortality. It is more present in premature infants and can also happen in term and late preterm neonates. It may affect any segment of the small intestine or colon. However, most commonly influences the terminal ileum and proximal ascending colon. This disease might damage the entire bowel, which can be irreversible. Intestinal mucosal defects cause the migration of large numbers of inflammatory cells into the gut lumen. Extensive mucosal affection results in increased calprotectin levels.
This study aimed to investigate the role of fecal calprotectin as a non-invasive marker in the diagnosis of NEC for the better management of infants with NEC.
Methods: This case-control cross-sectional study was performed in two groups. Group 1 was the case group consisting of the neonates admitted at Suez Canal University Hospital, Neonatal Intensive Care Unit with a clinical diagnosis of NEC. All cases were evaluated by Bell's staging criteria. Group 2 included control subjects. All the studied subjects had complete medical history, full physical examination, and laboratory investigations, including complete blood count, stool analysis, and C-reactive protein. Radiological examination entailed chest X-ray and erect abdomen X-ray, abdominal ultrasonography, and the measurement of stool calprotectin.
Results: Fecal calprotectin level showed a positive strong correlation with NEC stages and this was statistically significant. Regarding the sequels of NEC, our study showed a positive correlation between NEC stage and fecal calprotectin level with r of 0.911 and P-value of < 0.001. The mean level of calprotectin in stage Ιa was 226.9 µg/g with the maximum in patients affected with stage ΙΙb (875 µg/g).
Conclusion: According to the findings of this study, fecal calprotectin can be used as a marker in the diagnosis of NEC and has a strong positive correlation with the severity of NEC.


1. Kawase Y, Ishii T, Arai H, Uga N. Gastrointestinal perforation in very low-birthweight infants. Pediatr Int. 2006; 48(6):599-603.
2. Hunter CJ, Bean JF. Cronobacter: an emerging opportunistic pathogen associated with neonatal meningitis, sepsis and necrotizing enterocolitis. J Perinatol. 2013; 33(8):581-5.
 3. Aydemir G, Cekmez F, Tanju IA, Canpolat FE, Genc FA, Yildirim S, et al. Increased fecal calprotectin in preterm infants with necrotizing enterocolitis. Clin Lab. 2012; 58(7-8):841-4.
 4. Bode G, Lüken A, Kerkhoff C, Roth J, Ludwig S, Nacken W, et al. Interaction between S100A8/A9 and annexin A6 is involved in the calcium-induced cell surface exposition of S100A8/A9. J Biol Chem. 2008; 283(46):31776-84.
 5. Hunter CJ, Camerini V, Boyle A. Bacterial flora enhance intestinal injury and inflammation in the rat pup model of necrotizing enterocolitis. [Master Thesis]. Toronto: Childrens Hospital Los Angeles, CA; 2007.
 6. Bohnhorst B. Usefulness of abdominal ultrasound in diagnosing necrotising enterocolitis. Arch Dis Child Fetal Neonatal Ed. 2013; 98(5):F445-50.
 7. Wan-Huen P, Bateman D, Shapiro DM, Parravicini E. Packed red blood cell transfusion is an independent risk factor for necrotizing enterocolitis in premature infants. J Perinatol. 2013; 33(10):786-90.
8. Abdelwahab A, Khashana A, Ahmed N, Younis S. Correlation between insulin like growth factor -1 and anthropometric measurements of the premature infants. J Nepal Paediatr Soc. 2016; 36(1):24-7. 9. Khashana A, Saarela T, Rämet M, Hallman M. Cortisol intermediates and hydrocortisone responsiveness in critical neonatal disease. J Matern Fetal Neonatal Med. 2017; 30(14):1721-5.
 10. Khashana A, Ahmed H, Ahmed A, Abdelwahab A, Saarela T, Rämet M, et al. Cortisol precursors in neonates with vasopressor resistant hypotension in relationship to demographic characteristics. J Matern Fetal Neonatal Med. 2017; 31(18):2473-7.
 11. Khashana A, Ahmed E. Hyperdehydroepiandrosterone in neonates with hypoxic ischemic encephalopathy and circulatory collapse. Pediatr Neonatol. 2017; 58(6):504-8.
12. Moonen RM, Paulussen AD, Souren NY, Kessels AG, Rubio-Gozalbo ME, Villamor E. Carbamoyl phosphate synthetase polymorphisms as a risk factor for necrotizing enterocolitis. Pediatr Res. 2007; 62(2):188-90.
13. Treszl A, Héninger E, Kálmán A, Schuler A, Tulassay T, Vásárhelyi B, et al. Lower prevalence of IL-4 receptor alpha-chain gene G variant in very-lowbirth-weight infants with necrotizing enterocolitis. J Pediatr Surg. 2003; 38(9):1374-8.
14. Røseth AG, Aadland E, Jahnsen J, Raknerud N. Assessment of disease activity in ulcerative colitis by faecal calprotectin, a novel granulocyte marker protein. Digestion. 1997; 58(2):176-80.
 15. Fagerhol MK. Calprotectin, a faecal marker of organic gastrointestinal abnormality. Lancet. 2000; 356(9244):1783-4.
 16. Permyakov EA, Kretsinger RH. Cell signaling, beyond cytosolic calcium in eukaryotes. J Inorg Biochem. 2009; 103(1):77-86.
17. Grimbaldeston MA, Geczy CL, Tedla N, Finlay-Jones JJ, Hart PH. S100A8 induction in keratinocytes by UVA-irradiation is dependent on reactive oxygen intermediates. J Invest Dermatol. 2003; 121(5): 1168-74.
18. Albanna EA, Ahmed HS, Awad HA. Stool calprotectin in necrotizing enterocolitis. J Clin Neonatol. 2014; 3(1):16-9.
 19. Buderer N. Statistical methodology: I. incorporating the prevalence of disease into the sample size calculation for sensitivity and specificity. Acad Emerg Med. 1996; 3(9):895-900 .
20. Schnabl KL, Van Aerde JE, Thomson AB, Clandinin MT. Necrotizing enterocolitis: a multifactorial disease with no cure. World J Gastroenterol. 2008; 14(14):2142-61.
21. Carroll D, Corfield A, Spicer R, Cairns P. Faecal calprotectin concentrations and diagnosis of necrotising enterocolitis. Lancet. 2003; 361 (93554):310-1.
22. Nissen AC, van Gils CE, Menheere PP, Van den Neucker AM, van der Hoeven MA, Forget PP. Fecal calprotectin in healthy term and preterm infants. J Pediatr Gastroenterol Nutr. 2004; 38(1):107-8. 23. Reisinger KW, Van der Zee DC, Brouwers HA, Kramer BW, van Heurn LW, Buurman WA, et al. Noninvasive measurement of fecal calprotectin and serum amyloid A combined with intestinal fatty acid-binding protein in necrotizing enterocolitis. J Pediatr Surg. 2012; 47(9):1640-5.
24. Selimoğlu MA, Temel I, Yıldırım Ç, Özyaln F, Aktaş M, Karabiber H. The role of fecal calprotectin and lactoferrin in the diagnosis of necrotizing enterocolitis. Pediatr Crit Care Med. 2012; 13(4):452-4. 25. Yoon JM, Park JY, Ko KO, Lim JW, Cheon EJ, Kim HJ. Fecal calprotectin concentration in neonatal necrotizing enterocolitis. Korean J Pediatr. 2014; 57(8):351-6.
 26. Rougé C, Butel MJ, Piloquet H, Ferraris L, Legrand A, Vodovar M, et al. Fecal calprotectin excretion in preterm infants during the neonatal period. PLoS One. 2010; 5(6):e11083.
 27. Moussa R, Khashana A, Kamel N, Elsharqawy SE. Fecal calprotectin levels in preterm infants with and without feeding intolerance. J Pediatr (Rio J). 2016; 92(5):486-92.
 28. Khashana A, Ayoub A, Younes S, Abdelrahman A. Ischemia modified albumin in early neonatal sepsis. Infect Dis (Lond). 2016; 48(6):488-9.
 29. Josefsson S, Bunn SK, Domellöf M. Fecal calprotectin in very low birth weight infants. J Pediatr Gastroenterol Nutr. 2007; 44(4):407-13.
30. Thuijls G, Derikx JP, van Wijck K, Zimmermann LJ, Degraeuwe PL, Mulder TL, et al. Non-invasive markers for early diagnosis and determination of the severity of necrotizing enterocolitis. Ann Surg. 2010; 251(6):1174-80.