Fecal Calprotectin: A Screening Marker for the Early Detection of Necrotizing Enterocolitis among Children in Egypt

Document Type : Original Article

Authors

1 Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt.

2 Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Abstract

Background: Necrotizing enterocolitis (NEC) is a lethal disease affecting newborns with significant morbidity and mortality rates. Moreover, it is the most eminent gastrointestinal threat affecting premature newborns. Unfortunately, early symptoms and signs are usually vague; therefore, there is a special demand for sensitive biomarkers in this regard. This study aimed to investigate the role of fecal calprotectin in stage I NEC and identify specific cut off value at this stage to differentiate stage I NEC from other gastrointestinal disorders.
Methods: This cross-sectional study was conducted at New Children Hospital, Cairo University, Egypt. In total, 100 newborns were included in this study who were assigned to the patient group with stage I NEC (n=60) and control group (n=40)with age and gender-matched newborns.Fecal calprotectin level was assessed using an enzyme-linked immunosorbent assay in both groups. Follow up of the patient group was performed for the development of stage II or III NEC.
Results: The patient group obtained significantly elevated levels of fecal calprotectin, compared to the control group (P=0.000). Within the patient group, 43 (71.66%) newborns developed stage II or III NEC, whereas 17 (28.33%) cases developed no NEC. In addition, the level of fecal calprotectin was significantly higher in the group who developed stage II or III NEC (P=0.001). According to the receiver operating characteristic (ROC) curve, the cutoff value of 109.5 μg/g feces showed 100% sensitivity and specificity, and the area under the ROC curvewas equal to 1 in differentiating NEC from other conditions.
Conclusion: The study showed that fecal calprotectin can be used as a sensitive and specific marker for the early detection of necrotizing enterocolitis.

Keywords

References

1. Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med. 2011;364(3):255-64.
2. Song R, Subbarao GC, Maheshwari A. Haematological abnormalities in neonatal necrotizing enterocolitis. J Matern Fetal Neonatal Med. 2012;25(4):14-7.
3. Berrington JE, Hearn RI, Bythell M, Wright C, Embleton ND. Deaths in preterm infants: changing pathology over 2 decades. J Pediatr. 2012; 160(1):49-53.
4. Rees CM, Pierro A, Eaton S. Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis. Arch Dis ChildFetal Neonatal Ed. 2007;92(3):F193-8.
5. Basu S. Neonatal sepsis: the gut connection. Eur J Clin Microbiol Infect Dis. 2015;34(2):215-22.
6. Cho SX, Berger PJ, Nold-Petry CA, Nold MF. The immunological landscape in necrotising enterocolitis. Expert Rev Mol Med. 2016;18:12.
7. Patole S. Microbiota and necrotizing enterocolitis. Nestle Nutr Inst Workshop Ser. 2017; 88:81-94.
8. Samuels N, van de Graaf RA, de Jonge RC, Reiss IK, Vermeulen MJ. Risk factors for necrotizing enterocolitis in neonates: a systematic review of prognostic studies. BMC Pediatr. 2017;17(1):105.
9. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall RI, Barton LE, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978;187(1):1-7.
10. Epelman M, Daneman A, Navarro OM, Morag I, Moore AM, Kim JH, et al. Necrotizing enterocolitis: review of state-of-the-art imaging findings with pathologic correlation. Radiographics. 2007;27(2): 285-305.
11. Chawla S, Natarajan G, Shankaran S, Pappas A, Stoll BJ, Carlo WA, et al. Association of neurodeve-lopmental outcomes and neonatal morbidities of extremely premature infants with differential exposure to antenatal steroids. JAMA Pediatr. 2016;170(12):1164-72.
12. AlFaleh K, Anabrees J. Probiotics for prevention of necrotizing enterocolitis in preterm infants. EvidBased Child Health Cochrane Rev J. 2014; 9(3):584-671.
13. Young C, Sharma R, Handfield M, Mai V, Neu J. Biomarkers for infants at risk for necrotizing enterocolitis: clues to prevention? Pediatr Res. 2009;65(7):91-7.
14. Hällström M, Koivisto AM, Janas M, Tammela O. Laboratory parameters predictive of developing necrotizing enterocolitis in infants born before 33 weeks of gestation. J Pediatr Surg. 2006;41(4):792-8.
15. Däbritz J, Jenke A, Wirth S, Foell D. Fecal phagocyte-specific S100A12 for diagnosing necrotizing enterocolitis. J Pediatr. 2012;161(6):1059-64.
16. Steinbakk M, Naess-Andresen CF, Lingaas E, Dale I, Brandtzaeg P, Fagerhol MK. Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin. Lancet. 1990; 336(8718):763-5.
17. Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, et al. Metal chelation and inhibition of bacterial growth in tissue abscesses. Science. 2008;319(5865):962-5.
18. Mao R, Xiao YL, Gao X, Chen BL, He Y, Yang L, et al. Fecal calprotectin in predicting relapse of inflammatory bowel diseases: a meta-analysis of prospective studies. Inflamm Bowel Dis. 2012; 18(10):1894-9.
19. Siddiqui I, Majid H, Abid S. Update on clinical and research application of fecal biomarkers for gastrointestinal diseases. World J Gastrointest Pharmacol Ther. 2017;8(1):39-46.
20. Holtman GA, Lisman-van Leeuwen Y, Day AS, Fagerberg UL, Henderson P, Leach ST, et al. Use of laboratory markers in addition to symptoms for diagnosis of inflammatory bowel disease in children: a meta-analysis of individual patient data.
JAMA Pediatr. 2017;171(10):984-91.
21. Zhang M, Zhang X, Zhang J. Diagnostic value of fecal calprotectin in preterm infants with necrotizing enterocolitis. Clin Lab. 2016;62(5):863-9.
22. Pergialiotis V, Konstantopoulos P, Karampetsou N, Koutaki D, Gkioka E, Perrea DN, et al. Calprotectin levels in necrotizing enterocolitis: a systematic review of the literature. Inflamm Res. 2016; 65(11):847-52.
23. Hintz SR, Kendrick DE, Stoll BJ, Vohr BR, Fanaroff AA, Donovan EF, et al. Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics. 2005;115(3):696-703.
24. Kastenberg ZJ, Sylvester KG. The surgical management of necrotizing enterocolitis. Clin Perinatol. 2013;40(1):135-48.
25. Reisinger KW, Van der Zee DC, Brouwers HA, Kramer BW, van Heurn LE, 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.
26. Campeotto F, Kalach N, Lapillonne A, Butel MJ, Dupont C, Kapel N. Time course of faecal calprotectin in preterm newborns during the first month of life. Acta Paediatr. 2007;96(10):1531-3.
27. Moussa R, Khashana A, Kamel N, Elsharqawy SE. Fecal calprotectin levels in preterm infants with and without feeding intolerance. J Pediatr. 2016;92(5): 486-92.
28. Boo NY, Soon CC, Lye MS. Risk factors associated with feed intolerance in very low birthweight infants following initiation of enteral feeds during the first 72 hours of life. J Trop Pediatr. 2000; 46(5):272-7.
29. Ahle M, Drott P, Elfvin A, Andersson RE. Maternal, fetal and perinatal factors associated with necrotizing enterocolitis in Sweden. A national case-control study. PloS One. 2018;13(3):e0194352.
30. Fox JR, Thacker LR, Hendricks-Muñoz KD. Early detection tool of intestinal dysfunction: impact on necrotizing enterocolitis severity. Am J Perinatol. 2015;32(10):927-32.
31. Maayan-Metzger A, Itzchak A, Mazkereth R, Kuint J. 2004. Necrotizing enterocolitis in full-term infants: case-control study and review of the literature. J Perinatol. 24:494–499.
32. Manogura AC, Turan O, Kush ML, Berg C, Bhide A, Turan S, et al. Predictors of necrotizing enterocolitis in preterm growth-restricted neonates. Am J Obstet Gynecol. 2008;198(6):638-e1-5.
33. Lambert DK, Christensen RD, Henry E, Besner GE, Baer VL, Wiedmeier SE, et al. Necrotizing enterocolitis in term neonates: data from a multihospital health-care system. J Perinatol. 2007;27(7):437-43.
34. D'incà R, Dal Pont E, Di Leo V, Benazzato L, Martinato M, Lamboglia F, et al. Can calprotectin predict relapse risk in inflammatory bowel disease? Am JGastroenterol. 2008;103(8):2007-14.
35. Cui X, Li J. Fecal calprotectin levels in preterm infants during the early neonatal period. Zhongguo Dang Dai Er Ke Za Zhi. 2012;14(3):165-8.
36. Josefsson S, Bunn SK, Domellöf M. Fecal calprotectin in very low birth weight infants. J Pediatr
Gastroenterol Nutr. 2007;44(4):407-13.
37. 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.
Iranian Journal of Neonatology
Volume 11, Issue 2
May 2020
Pages 1-9

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