Early Biomarkers in Neonatal Necrotizing Enterocolitis: A Pilot Study
Main Article Content
Keywords
necrotizing enterocolitis, neonate, fecal calprotectin, biomarkers, procalcitonin, interleukin 18
Abstract
Background
Necrotizing enterocolitis (NEC) is a frequent serious disease of the digestive system in neonates. It is considered as an important cause of serious neonatal complication and death. Therefore, its early suspicion and proper management are important.
Aim
Early and sensitive detection of neonatal NEC through determination of levels of fecal calprotectin (FCP), serum levels of procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), epithelial neutrophil activating peptide 78 (ENA-78), and interleukin 18 (IL-18).
Method
This prospective case control study was conducted in Tanta University Hospital from June 2016 to March 2018. The study included 20 healthy neonates (control group) and 20 NEC newborn patients. They were all subjected to the measurement of levels of FCP and serum levels of hs-CRP, PCT, ENA- 78, IL-18, Malondialdehyde (MDA), and total antioxidant capacity (TAC). Receiver operating characteristic (ROC) curve analysis was conducted for FCP, ENA-78, PCT, hs-CRP, and IL-18.
Results
The study found a detectable increase in FCP level and serum levels of hs-CRP, PCT, ENA-78, IL-18, and MDA in NEC group in comparison to their levels in the control group. Also, it found a detectable decline in the levels of TAC in comparison to its level in the control group.
Conclusion
FCP, ENA-78, and PCT can be considered as early markers for diagnosis of NEC.
Necrotizing enterocolitis (NEC) is a frequent serious disease of the digestive system in neonates. It is considered as an important cause of serious neonatal complication and death. Therefore, its early suspicion and proper management are important.
Aim
Early and sensitive detection of neonatal NEC through determination of levels of fecal calprotectin (FCP), serum levels of procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), epithelial neutrophil activating peptide 78 (ENA-78), and interleukin 18 (IL-18).
Method
This prospective case control study was conducted in Tanta University Hospital from June 2016 to March 2018. The study included 20 healthy neonates (control group) and 20 NEC newborn patients. They were all subjected to the measurement of levels of FCP and serum levels of hs-CRP, PCT, ENA- 78, IL-18, Malondialdehyde (MDA), and total antioxidant capacity (TAC). Receiver operating characteristic (ROC) curve analysis was conducted for FCP, ENA-78, PCT, hs-CRP, and IL-18.
Results
The study found a detectable increase in FCP level and serum levels of hs-CRP, PCT, ENA-78, IL-18, and MDA in NEC group in comparison to their levels in the control group. Also, it found a detectable decline in the levels of TAC in comparison to its level in the control group.
Conclusion
FCP, ENA-78, and PCT can be considered as early markers for diagnosis of NEC.
References
1. Qian T, Zhang R, Zhu L, Shi P, Yang J, Yang C et al. Necrotizing enterocolitis in low birth weight infants in China: Mortality risk factors expressed by birth weight categories, Pediatrics & Neonatology.2017; 58(6):509–515.
2. Hourigan SK, Ta A, Wong WS, Clemency NC, Provenzano MG, Baveja R, et al. The microbiome in necrotizing enterocolitis: A case report in twins and minireview. Clin Ther. 2016;38:747?53.
3. Cassir N, Simeoni U, La Scola B. Gut microbiota and the pathogenesis of necrotizing enterocolitis in preterm neonates. Future Microbiol. 2016;11:273?92.
4. Haque KN. Necrotizing enterocolitis - Some things old and some things new: A comprehensive review. 2016;5 (2)79-90
5. Niño DF, Sodhi CP, Hackam DJ. Necrotizing enterocolitis: new insights into pathogenesis and mechanisms Nat Rev Gastroenterol Hepatol. 2016; 13(10): 590–600.
6. Moldoveanu AC, Diculescu M, Braticevici CF. Cytokines in inflammatory bowel disease. Rom J Intern Med. 2015;53(2):118-27.
7. Yang T, Wang S, Zheng Q , Wang L, Li Q, Wei M et al. Increased plasma levels of epithelial neutrophil-activating peptide 78/CXCL5 during the remission of Neuromyelitis optica. BMC Neurol. 2016:11;16:96.
8. Perrone S, Tataranno ML, Santacroce A, Negro S, Buonocore G. The role of oxidative stress on necrotizing enterocolitis in very low birth weight infants. Curr Pediatr Rev. 2014;10(3):202-7.
9. Abdel Ghany EA, Alsharany W, Ali AA, Youness ER, Hussein JS. Anti-oxidant profiles and markers of oxidative stress in preterm neonates.Paediatr Int Child Health. 2016;36(2):134-40.
10. Quadir AF, Britton PN. Procalcitonin and C-reactive protein as biomarkers for neonatal bacterial infection. J Paediatr Child Health. 2018;54(6):695-699.
11. Pravin Charles MV, Kalaivani R, Venkatesh S, Kali A, Seetha KS. Evaluation of procalcitonin as a diagnostic marker in neonatal sepsis. Indian J Pathol Microbiol. 2018;61(1):81-84.
12. Ganesan P, Shanmugam P, Sattar SB, Shankar SL. Evaluation of IL-6, CRP and hs-CRP as Early Markers of Neonatal Sepsis. J Clin Diagn Res. 2016;10(5):13-27.
13. Hahn WH, Song JH, Kim H, Park S. Is procalcitonin to C-reactive protein ratio useful for the detection of late onset neonatal sepsis? J Matern Fetal Neonatal Med. 2018 ;31(6):822-826.
14. Nakayuenyongsuk W, Christofferson M, Stevenson DK, Sylvester K, Lee HC, Park KT. Point-of-Care Fecal Calprotectin Monitoring in Preterm Infants at Risk for Necrotizing Enterocolitis. J Pediatr. 2018;196:98-103.
15. Zhang M, Zhang X, Zhang J. Diagnostic Value of Fecal Calprotectin in Preterm Infants with Necrotizing Enterocolitis. Clin Lab. 2016;62(5):863-9.
16. MacQueen BC, Christensen RD, Yost CC, Lambert DK, Baer VL, Sheffield MJ, et al. Elevated fecal calprotectin levels during necrotizing enterocolitis are associated with activated neutrophils extruding neutrophil extracellular traps. J.Perinatol. 2016;36(10):862-9.
17. Bin-Nun A, Booms C, Sabag N, Mevorach R, Algur N, Hammerman C. Rapid fecal calprotectin (FC) analysis: point of care testing for diagnosing early necrotizing enterocolitis. Am J Perinatol. 2015;32(4):337-42.
18. Neu J. Necrotizing enterocolitis: the search for a unifying pathogenic theory leading to prevention. Pediatr Clin North Am. 1996;43(2):409-32.
19. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95(2): 351-358.
20. Aydemir C, Dilli D, Uras N, Ulu HO, Oguz SS, Erdeve O, et al. Total oxidant status and oxidative stress are increased in infants with necrotizing enterocolitis. Am J Perinatol. 2015;32(4):337-42.
21. Cho SX, Berger PJ, Nold-Petry CA, Nold MF. The immunological landscape in necrotising enterocolitis Expert Rev Mol Med. 2016:24;18:e12.
22. Dinarello CA. Interleukin-18. Methods 1999;19:121-32.
23. Girard C, Rech J, Brown M, Allali D, Roux-Lombard P, Spertini F et al. Elevated serum levels of free interleukin-18 in adult-onset Still’s disease Rheumatology, 2106:55(12):2237–2247.
24. Halpern MD, Khailova L, Molla-Hosseini D, Arganbright K, Reynolds C, Yajima M, et al. Decreased development of necrotizing enterocolitis in IL-18-deficient mice Am J Physiol Gastrointest Liver Physiol.2008; 294: 20–26.
25. Keelan JA, Yang J, Romero RJ, Chaiworapongsa T, Marvin KW, Sato TA. Epithelial Cell-Derived Neutrophil-Activating Peptide-78 Is Present in Fetal Membranes and Amniotic Fluid at Increased Concentrations with Intra-amniotic Infection and Preterm Delivery. Biology of Reproduction. 2004: 70(1): 253–259.
26. Mostafa GA, Al-Ayadhi LY. The possible link between elevated serum levels of epithelial cell-derived neutrophil-activating peptide-78 (ENA-78/CXCL5) and autoimmunity in autistic children. Behav Brain Funct. 2015:19;11:11.
27. Lu P, Sodhi CP, Jia H, Shaffiey S, Good M, Branca MF et al. Animal models of gastrointestinal and liver diseases. Animal models of necrotizing enterocolitis: pathophysiology, translational relevance, and challenges. Am J Physiol Gastrointest Liver Physiol. 2014 Jun 1; 306(11):G917-28
28. Ozsurekci Y, Aykac K. Oxidative Stress Related Diseases in Newborns Oxid Med Cell Longev. 2016; 2016: 2768365.
29. Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev. 2014;94(2):329-54.
30. Zhang H, Chen J, Wang Y, Deng C, Li L, Guo C. Predictive factors and clinical practice profile for strictures post-necrotising enterocolitis. Medicine (Baltimore). 2017 ;96(10):e6273.
31. Cetinkaya M, Ozkan H, Köksal N, Akaci O, Ozgür T. Comparison of the efficacy of serum amyloid A, C-reactive protein, and procalcitonin in the diagnosis and follow-up of necrotizing enterocolitis in premature infants. J Pediatr Surg. 2011;46 (8):1482-9.
32. Gaudin A, Farnoux C, Bonnard A, Alison M, Maury L, Biran V, Baud O. Necrotizing enterocolitis (NEC) and the risk of intestinal stricture: the value of C-reactive protein. PLoS One. 2013:11;8(10):e76858.
33. Sorokin Y, Romero R, Mele L, Iams JD, Peaceman AM, Leveno KJ, et al. Umbilical cord serum interleukin-6, C-reactive protein, and myeloperoxidase concentrations at birth and association with neonatal morbidities and long-term neurodevelopmental outcomes. Am J Perinatol. 2014;31(8):717-26.
34. 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.
35. Selimo?lu MA, Temel I, Y?ld?r?m Ç, Özyaln F, Akta? 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.
2. Hourigan SK, Ta A, Wong WS, Clemency NC, Provenzano MG, Baveja R, et al. The microbiome in necrotizing enterocolitis: A case report in twins and minireview. Clin Ther. 2016;38:747?53.
3. Cassir N, Simeoni U, La Scola B. Gut microbiota and the pathogenesis of necrotizing enterocolitis in preterm neonates. Future Microbiol. 2016;11:273?92.
4. Haque KN. Necrotizing enterocolitis - Some things old and some things new: A comprehensive review. 2016;5 (2)79-90
5. Niño DF, Sodhi CP, Hackam DJ. Necrotizing enterocolitis: new insights into pathogenesis and mechanisms Nat Rev Gastroenterol Hepatol. 2016; 13(10): 590–600.
6. Moldoveanu AC, Diculescu M, Braticevici CF. Cytokines in inflammatory bowel disease. Rom J Intern Med. 2015;53(2):118-27.
7. Yang T, Wang S, Zheng Q , Wang L, Li Q, Wei M et al. Increased plasma levels of epithelial neutrophil-activating peptide 78/CXCL5 during the remission of Neuromyelitis optica. BMC Neurol. 2016:11;16:96.
8. Perrone S, Tataranno ML, Santacroce A, Negro S, Buonocore G. The role of oxidative stress on necrotizing enterocolitis in very low birth weight infants. Curr Pediatr Rev. 2014;10(3):202-7.
9. Abdel Ghany EA, Alsharany W, Ali AA, Youness ER, Hussein JS. Anti-oxidant profiles and markers of oxidative stress in preterm neonates.Paediatr Int Child Health. 2016;36(2):134-40.
10. Quadir AF, Britton PN. Procalcitonin and C-reactive protein as biomarkers for neonatal bacterial infection. J Paediatr Child Health. 2018;54(6):695-699.
11. Pravin Charles MV, Kalaivani R, Venkatesh S, Kali A, Seetha KS. Evaluation of procalcitonin as a diagnostic marker in neonatal sepsis. Indian J Pathol Microbiol. 2018;61(1):81-84.
12. Ganesan P, Shanmugam P, Sattar SB, Shankar SL. Evaluation of IL-6, CRP and hs-CRP as Early Markers of Neonatal Sepsis. J Clin Diagn Res. 2016;10(5):13-27.
13. Hahn WH, Song JH, Kim H, Park S. Is procalcitonin to C-reactive protein ratio useful for the detection of late onset neonatal sepsis? J Matern Fetal Neonatal Med. 2018 ;31(6):822-826.
14. Nakayuenyongsuk W, Christofferson M, Stevenson DK, Sylvester K, Lee HC, Park KT. Point-of-Care Fecal Calprotectin Monitoring in Preterm Infants at Risk for Necrotizing Enterocolitis. J Pediatr. 2018;196:98-103.
15. Zhang M, Zhang X, Zhang J. Diagnostic Value of Fecal Calprotectin in Preterm Infants with Necrotizing Enterocolitis. Clin Lab. 2016;62(5):863-9.
16. MacQueen BC, Christensen RD, Yost CC, Lambert DK, Baer VL, Sheffield MJ, et al. Elevated fecal calprotectin levels during necrotizing enterocolitis are associated with activated neutrophils extruding neutrophil extracellular traps. J.Perinatol. 2016;36(10):862-9.
17. Bin-Nun A, Booms C, Sabag N, Mevorach R, Algur N, Hammerman C. Rapid fecal calprotectin (FC) analysis: point of care testing for diagnosing early necrotizing enterocolitis. Am J Perinatol. 2015;32(4):337-42.
18. Neu J. Necrotizing enterocolitis: the search for a unifying pathogenic theory leading to prevention. Pediatr Clin North Am. 1996;43(2):409-32.
19. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95(2): 351-358.
20. Aydemir C, Dilli D, Uras N, Ulu HO, Oguz SS, Erdeve O, et al. Total oxidant status and oxidative stress are increased in infants with necrotizing enterocolitis. Am J Perinatol. 2015;32(4):337-42.
21. Cho SX, Berger PJ, Nold-Petry CA, Nold MF. The immunological landscape in necrotising enterocolitis Expert Rev Mol Med. 2016:24;18:e12.
22. Dinarello CA. Interleukin-18. Methods 1999;19:121-32.
23. Girard C, Rech J, Brown M, Allali D, Roux-Lombard P, Spertini F et al. Elevated serum levels of free interleukin-18 in adult-onset Still’s disease Rheumatology, 2106:55(12):2237–2247.
24. Halpern MD, Khailova L, Molla-Hosseini D, Arganbright K, Reynolds C, Yajima M, et al. Decreased development of necrotizing enterocolitis in IL-18-deficient mice Am J Physiol Gastrointest Liver Physiol.2008; 294: 20–26.
25. Keelan JA, Yang J, Romero RJ, Chaiworapongsa T, Marvin KW, Sato TA. Epithelial Cell-Derived Neutrophil-Activating Peptide-78 Is Present in Fetal Membranes and Amniotic Fluid at Increased Concentrations with Intra-amniotic Infection and Preterm Delivery. Biology of Reproduction. 2004: 70(1): 253–259.
26. Mostafa GA, Al-Ayadhi LY. The possible link between elevated serum levels of epithelial cell-derived neutrophil-activating peptide-78 (ENA-78/CXCL5) and autoimmunity in autistic children. Behav Brain Funct. 2015:19;11:11.
27. Lu P, Sodhi CP, Jia H, Shaffiey S, Good M, Branca MF et al. Animal models of gastrointestinal and liver diseases. Animal models of necrotizing enterocolitis: pathophysiology, translational relevance, and challenges. Am J Physiol Gastrointest Liver Physiol. 2014 Jun 1; 306(11):G917-28
28. Ozsurekci Y, Aykac K. Oxidative Stress Related Diseases in Newborns Oxid Med Cell Longev. 2016; 2016: 2768365.
29. Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev. 2014;94(2):329-54.
30. Zhang H, Chen J, Wang Y, Deng C, Li L, Guo C. Predictive factors and clinical practice profile for strictures post-necrotising enterocolitis. Medicine (Baltimore). 2017 ;96(10):e6273.
31. Cetinkaya M, Ozkan H, Köksal N, Akaci O, Ozgür T. Comparison of the efficacy of serum amyloid A, C-reactive protein, and procalcitonin in the diagnosis and follow-up of necrotizing enterocolitis in premature infants. J Pediatr Surg. 2011;46 (8):1482-9.
32. Gaudin A, Farnoux C, Bonnard A, Alison M, Maury L, Biran V, Baud O. Necrotizing enterocolitis (NEC) and the risk of intestinal stricture: the value of C-reactive protein. PLoS One. 2013:11;8(10):e76858.
33. Sorokin Y, Romero R, Mele L, Iams JD, Peaceman AM, Leveno KJ, et al. Umbilical cord serum interleukin-6, C-reactive protein, and myeloperoxidase concentrations at birth and association with neonatal morbidities and long-term neurodevelopmental outcomes. Am J Perinatol. 2014;31(8):717-26.
34. 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.
35. Selimo?lu MA, Temel I, Y?ld?r?m Ç, Özyaln F, Akta? 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.
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Dec 23, 2019
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Elfarargy, M. S., El Farargy, M. S., Mohamed Atef, M., El-Deeb, O. S., Elsharaby, R. M., & Elfattah Elhady, H. A. (2019). Early Biomarkers in Neonatal Necrotizing Enterocolitis: A Pilot Study. Journal of Population Therapeutics and Clinical Pharmacology, 26(3), e1-e8. https://doi.org/10.15586/jptcp.v26i3.602
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