Abstract
Objective
Calprotectin is an antimicrobial protein found in stool when released by granulocytes. We sought to create stool calprotectin reference ranges in preterm neonates and to evaluate whether levels exceeding the upper reference interval are diagnostic for necrotizing enterocolitis (NEC).
Study design
Stool calprotectin was measured in premature neonates without gastrointestinal pathology to create reference intervals. For comparison, levels from infants undergoing “rule out NEC” evaluations were plotted on these reference intervals.
Results
Stool calprotectin reference intervals were created according to gestational age at birth and corrected gestational age. Levels during “rule out NEC” evaluations were more often above the upper reference interval with NEC vs. those without NEC.
Conclusions
Stools from preterm neonates have a higher range of calprotectin than stools from healthy term neonates. In evaluating preterm neonates for NEC with stool calprotectin, a calprotectin upper reference interval that incorporates corrected gestational age best predicts the diagnosis of NEC.
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References
Bunn SK, Bisset WM, Main MJ, Golden BE. Fecal calprotectin as a measure of disease activity in childhood inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2001;32:171–7.
Waugh N, Cummins E, Royle P, Kandala NB, Shyangdan D, Arasaradnam R, et al. Faecal calprotectin testing for differentiating amongst inflammatory and non-inflammatory bowel diseases: systematic review and economic evaluation. Health Technol Assess. 2013;17:xv–xix, 1–211.
Wright EK, De Cruz P, Gearry R, Day AS, Kamm MA. Fecal biomarkers in the diagnosis and monitoring of Crohn’s disease. Inflamm Bowel Dis. 2014;20:1668–77.
Alibrahim B, Aljasser MI, Salh B. Fecal calprotectin use in inflammatory bowel disease and beyond: a mini-review. Can J Gastroenterol Hepatol. 2015;29:157–63.
Carroll D, Corfield A, Spicer R, Cairns P. Faecal calprotectin concentrations and diagnosis of necrotising enterocolitis. Lancet. 2003;361:310–1.
Josefsson S, Bunn SK, Domellöf M. Fecal calprotectin in very low birth weight infants. J Pediatr Gastroenterol Nutr. 2007;44:407–13.
Yang Q, Smith PB, Goldberg RN, Cotten CM. Dynamic change of fecal calprotectin in very low birth weight infants during the first month of life. Neonatology. 2008;94:267–71.
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;32:337–42.
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;36:862–9.
Horowitz GL. Reference intervals: practical aspects. EJIFCC. 2008;19:95–105.
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;58:841–4.
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377–81.
Yoon JM, Park JY, Ko KO, Lim JW, Cheon EJ, Kim HJ. Fecal calprotectin concentration in neonatal necrotizing enterocolitis. Korean J Pediatr. 2014;7:351–6.
Li F, Ma J, Geng S, Wang J, Liu J, Zhang J, et al. Fecal calprotectin concentrations in healthy children aged 1–18 months. PLoS ONE. 2015;10:e0119574.
Moussa R, Khashana A, Kamel N, Elsharqawy SE. Fecal calprotectin levels in preterm infants with and without feeding intolerance. J Pediatr. 2016;92:486–92.
Levy O. Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat Rev Immunol. 2007;7:379–90.
La Rosa PS, Warner BB, Zhou Y, Weinstock GM, Sodergren E, Hall-Moore CM, et al. Patterned progression of bacterial populations in the premature infant gut. Proc Natl Acad Sci USA. 2014;111:12522–7.
Sullivan S, Schanler RJ, Kim JH, Patel AL, Trawöger R, Kiechl-Kohlendorfer U, et al. An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr. 2010;156:562–7.e1.
Cristofalo EA, Schanler RJ, Blanco CL, Sullivan S, Trawoeger R, Kiechl-Kohlendorfer U. et al. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. J Pediatr. 2013;163:1592–5.
Panczuk JK, Unger S, Francis J, Bando N, Kiss A, O’Connor DL. Introduction of bovine-based nutrient fortifier and gastrointestinal inflammation in very low birth weight infants as measured by fecal calprotectin. Breastfeed Med. 2016;11:2–5.
Yost CC, Schwertz H, Cody MJ, Wallace JA, Campbell RA, Vieira-de-Abreu A, et al. Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation. J Clin Invest. 2016;126:3783–379.
Hwang JB, Song JY, Kang YN, Kim SP, Suh SI, Kam S, Choi WJ. The significance of gastric juice analysis for a positive challenge by a standard oral challenge test in typical cow’s milk protein-induced enterocolitis. J Korean Med Sci. 2008;23:251–5.
Christensen RD, Lambert DK, Gordon PV, Baer VL, Gerday E, Henry E. Neonates presenting with bloody stools and eosinophilia can progress to two different types of necrotizing enterocolitis. J Perinatol. 2012;32:874–9.
Gordon PV, Swanson JR. Necrotizing enterocolitis is one disease with many origins and potential means of prevention. Pathophysiology. 2014;21:13–9.
Ho TT, Groer MW, Luciano AA, Schwartz A, Ji M, Miladinovic BS, et al. Red blood cell transfusions increase fecal calprotectin levels in premature infants. J Perinatol. 2015;35:837–41.
Zhang M, Zhang X, Zhang J. Diagnostic value of fecal calprotectin in preterm infants with necrotizing enterocolitis. Clin Lab. 2016;62:863–9.
Maheshwari A. Immunologic and hematological abnormalities in necrotizing enterocolitis. Clin Perinatol. 2015;42:567–85.
Abdel-Haie OM, Behiry EG, Abd Almonaem ER, Ahmad ES, Assar EH. Predictive and diagnostic value of serum intestinal fatty acid binding protein in neonatal necrotizing enterocolitis (case series). Ann Med Surg. 2017;6:9–13.
Esposito F, Mamone R, Di Serafino M, Mercogliano C, Vitale V, Vallone G. et al. Diagnostic imaging features of necrotizing enterocolitis: a narrative review. Quant Imaging Med Surg. 2017;7:336–44.
Acknowledgements
We thank the following medical directors and NICU research nurses for their assistance in collecting the stool samples; Elizabeth O’Brien, Intermountain Medical Center; Patrick Carroll, Dixie Regional Medical Center, Eva Livingston, Dixie Regional Medical Center; Trisha A. Marchant, RNC-NIC and Kimberlee Weaver Lewis, Intermountain Medical Center; Jennifer Elmont and Susan R. Christensen, Utah Valley Regional Medical Center; Kathryn D. Woodbury and Melody Parry, McKay-Dee Hospital.
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RS and JL are employees of ARUP laboratories where the calprotectin assays were run. The remaining authors declare that they have no conflict of interest.
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MacQueen, B.C., Christensen, R.D., Yost, C.C. et al. Reference intervals for stool calprotectin in preterm neonates and their utility for the diagnosis of necrotizing enterocolitis. J Perinatol 38, 1379–1385 (2018). https://doi.org/10.1038/s41372-018-0108-9
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DOI: https://doi.org/10.1038/s41372-018-0108-9
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