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Clinical utility of fecal calprotectin in monitoring disease activity and predicting relapse in pregnant patients with inflammatory bowel diseases

Published:March 20, 2020DOI:https://doi.org/10.1016/j.ejim.2020.03.015

      Highlights

      • Non-invasive monitoring of IBD during pregnancy is challenging.
      • Women with IBD attending a multidisciplinary clinic were prospectively recruited.
      • A total of 265 fecal calprotectin (FC) measurements were obtained in 157 IBD pregnancy patients.
      • FC levels were directly correlated with disease activity throughout pregnancy.
      • Increased FC levels were found to predict disease relapse later in the course of gestation .

      Abstract

      Objectives

      Inflammatory bowel diseases (IBDs) are commonly diagnosed in reproductive-aged women and can substantially affect pregnancy outcomes. Non-invasive monitoring of IBD during the prenatal course is particularly challenging as traditional laboratory biomarkers are often affected by pregnancy-related physiologic changes. We aimed to evaluate the role of fecal calprotectin (FC) in monitoring disease activity and predicting relapse among IBD women throughout gestation.

      Methods

      Women with IBD attending a multidisciplinary clinic for the preconception, antenatal and postnatal treatment were prospectively recruited during 2014–2018. FC levels were determined with an enzyme-linked immunoassay.

      Results

      A total of 265 FC (preconception, n = 41; 1st trimester, n = 48; 2nd trimester, n = 84; 3rd trimester, n = 76; postpartum, n = 16) measurements were obtained in 157 pregnancies. Higher FC concentrations were found in all time points in those with active disease than those in remission as assessed by either physician global assessment or disease clinical scores. FC levels were significantly correlated with physician global assessment and disease activity indices in all 5 periods of investigation. Excluding those with disease flare at the time of conception, disease relapse was encountered during the prenatal course in 40 (31.5%) of the remaining 127 pregnancies. FC levels were significantly higher in those who experienced a disease flare later in the course of gestation as compared to those who maintained clinical remission (median 341 vs. 224 μg/g, P = 0.04).

      Conclusion

      FC appears to be a reliable marker of ongoing disease activity throughout the prenatal course as well as a predictor of imminent disease flare among IBD pregnant patients.

      Keywords

      Abbreviations:

      cd (crohn's disease), Crp (c reactive protein), Fc (fecal calprotectin), Ga (gestational age), IBD (inflammatory bowel diseases), PGA (physician global assessment), UC (ulcerative colitis)
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      References

        • van der Woude C.J.
        • Ardizzone S.
        • Bengtson M.B.
        • et al.
        The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease.
        J Crohns Colitis. 2015; 9: 107-124
        • de Lima A.
        • Zelinkova Z.
        • van der Ent C.
        • et al.
        Tailored anti-TNF therapy during pregnancy in patients with IBD: maternal and fetal safety.
        Gut. 2016; 65: 1261-1268
        • Bengtson M.B.
        • Martin C.F.
        • Aamodt G.
        • et al.
        Inadequate gestational weight gain predicts adverse pregnancy outcomes in mothers with inflammatory bowel disease: results from a prospective US pregnancy cohort.
        Dig Dis Sci. 2017; 62: 2063-2069
        • Seirafi M.
        • de Vroey B.
        • Amiot A.
        • et al.
        Factors associated with pregnancy outcome in anti-TNF treated women with inflammatory bowel disease.
        Aliment Pharmacol Ther. 2014; 40: 363-373
        • Kammerlander H.
        • Nielsen J.
        • Kjeldsen J.
        • et al.
        The effect of disease activity on birth outcomes in a nationwide cohort of women with moderate to severe inflammatory bowel disease.
        Inflamm Bowel Dis. 2017; 23: 1011-1018
        • Mahadevan U.
        • Robinson C.
        • Bernasko N.
        • et al.
        Inflammatory bowel disease in pregnancy clinical care pathway: a report from the american gastroenterological association ibd parenthood project working group.
        Am J Obstet Gynecol. 2019; 220: 308-323
        • Nguyen G.C.
        • Seow C.H.
        • Maxwell C.
        • et al.
        The toronto consensus statements for the management of inflammatory bowel disease in pregnancy.
        Gastroenterology. 2016; 150: 734-757
        • Abdul Sultan A.
        • West J.
        • Ban L.
        • et al.
        Adverse pregnancy outcomes among women with inflammatory bowel disease: a population-based study from England.
        Inflamm Bowel Dis. 2016; 22: 1621-1630
        • Choden T.
        • Mandaliya R.
        • Charabaty A.
        • Mattar M.C
        Monitoring inflammatory bowel disease during pregnancy: current literature and future challenges.
        World J Gastrointest Pharmacol Ther. 2018; 9: 1-7
        • De Lima A.
        • Galjart B.
        • Wisse P.H.
        • et al.
        Does lower gastrointestinal endoscopy during pregnancy pose a risk for mother and child? A systematic review.
        BMC Gastroenterol. 2015; 15: 15
        • Ludvigsson J.F.
        • Lebwohl B.
        • Ekbom A.
        • et al.
        Outcomes of pregnancies for women undergoing endoscopy while they were pregnant: a nationwide cohort study.
        Gastroenterology. 2017; 152 (e9): 554-563
        • Shergill A.K.
        • Ben-Menachem T.
        • Chandrasekhara V.
        • et al.
        Guidelines for endoscopy in pregnant and lactating women.
        Gastrointest Endosc. 2012; 76: 18-24
        • Mumolo M.G.
        • Bertani L.
        • Ceccarelli L.
        • Laino G.
        • Di Fluri G.
        • Albano E.
        • et al.
        From bench to bedside: fecal calprotectin in inflammatory bowl diseases clinical setting.
        World J Gastroenterol. 2018; 24: 3681-3694
        • Gisbert J.P.
        • McNicholl A.G.
        Questions and answers on the role of faecal calprotectin as a biological marker in inflammatory bowel disease.
        Dig Liver Dis. 2009; 41: 56-66
        • Julsgaard M.
        • Hvas C.L.
        • Gearry R.B.
        • et al.
        Fecal calprotectin is not affected by pregnancy: clinical implications for the management of pregnant patients with inflammatory bowel disease.
        Inflamm Bowel Dis. 2017; 23: 1240-1246
        • Huang V.W.
        • Bal J.
        • Foshaug R.
        • et al.
        Fecal calprotectin is elevated with clinical disease activity during pregnancy in women with inflammatory bowel disease.
        J Crohns Colitis. 2015; 9: S215-S216
        • Shitrit A.B.
        • Granovsky-Grisaru S.
        • Adar T.
        • et al.
        Limitations in using fecal calprotectin as a biomarker of IBD disease activity during pregnancy.
        J Crohns Colitis. 2015; 9: S196
        • Kanis S.L.
        • de Lima A.
        • Van Oorschot V.
        • et al.
        Su1802 fecal calprotectine is a poor predictor of IBD relapse during pregnancy.
        Gastroenterology. 2016; 150: S556
        • Kammerlander H.
        • Nielsen J.
        • Kjeldsen J.
        • Knudsen T.
        • Gradel K.O.
        • Friedman S.
        • et al.
        Fecal calprotectin during pregnancy in women with moderate-severe inflammatory bowel disease.
        Inflamm Bowel Dis. 2018; 24: 839-848
        • Theede K.
        • Holck S.
        • Ibsen P.
        • et al.
        Fecal calprotectin predicts relapse and histological mucosal healing in ulcerative colitis.
        Inflamm Bowel Dis. 2016; 22: 1042-1048
        • Zhulina Y.
        • Cao Y.
        • Amcoff K.
        • Carlson M.
        • Tysk C.
        • Halfvarson J
        The prognostic significance of 34 faecal calprotectin in patients with inactive inflammatory bowel disease.
        Aliment Pharmacol 35 Ther. 2016; 44: 495-504
        • Diederen K.
        • Hoekman D.R.
        • Leek A.
        • Wolters V.M.
        • Hummel T.Z.
        • de Meij T.G.
        • et al.
        Raised faecal calprotectin is associated with subsequent symptomatic relapse, in children and adolescents with inflammatory bowel disease in clinical remission.
        Aliment Pharmacol Ther. 2017; 45 (951– 39 60)
        • Kennedy N.A.
        • Jones G.R.
        • Plevris N.
        • Patenden R.
        • Arnott I.D.
        • Lees C.W
        Association between level of fecal calprotectin and progression of Crohn's disease.
        Clin Gastroenterol Hepatol. 2019; (S1542-3565(19)30180-6)
        • Bar Gil Shitrit A.
        • Cohen Y.
        • Hassin O.
        • et al.
        Antenatal management for women with inflammatory bowel disease: experience from our "IBD MOM" clinic.
        Dig Dis Sci. 2018; 63: 1774-1781
        • Harvey R.F.
        • Bradshaw J.M.
        A simple index of Crohn's-disease activity.
        Lancet. 1980; 1: 514
        • Walsh A.J.
        • Ghosh A.
        • Brain A.O.
        • et al.
        Comparing disease activity indices in ulcerative colitis.
        J Crohns Colitis. 2014; 8: 318-325
        • Bálint A.
        • Berényi A.
        • Farkas K.
        • et al.
        Pregnancy does not affect fecal calprotectin concentration in healthy women.
        Turk J Gastroenterol. 2017; 28: 171-175
        • Naismith G.D.
        • Smith L.A.
        • Barry S.J.
        • et al.
        A prospective single-centre evaluation of the intra-individual variability of faecal calprotectin in quiescent Crohn's disease.
        Aliment Pharmacol Ther. 2013; 37: 613-621
        • Lasson A.
        • Stotzer P.O.
        • Ohman L.
        • et al.
        The intra-individual variability of faecal calprotectin: a prospective study in patients with active ulcerative colitis.
        J Crohns Colitis. 2015; 9: 26-32
        • Kostas A.
        • Siakavellas S.I.
        • Kosmidis C.
        • et al.
        Fecal calprotectin measurement is a marker of short-term clinical outcome and presence of mucosal healing in patients with inflammatory bowel disease.
        World J Gastroenterol. 2017; 23: 7387-7396
        • Klajnbard A.
        • Szecsi P.B.
        • Colov N.P.
        • et al.
        Laboratory reference intervals during pregnancy, delivery and the early postpartum period.
        Clin Chem Lab Med. 2010; 48: 237-248
        • Vermeire S.
        • Van A.G.
        • Rutgeerts P
        C-reactive protein as a marker for inflammatory bowel disease.
        Inflamm Bowel Dis. 2004; 10: 661-665
        • Peyrin-Biroulet L.
        • Sandborn W.
        • Sands B.E.
        • Reinisch W.
        • Bemelman W.
        • Bryant R.V.
        • et al.
        Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target.
        Am J Gastroenterol. 2015; 110: 1324-1338
        • Allen P.B.
        • Olivera P.
        • Emery P.
        • Moulin D.
        • Jouzeau J.Y.
        • Netter P.
        • et al.
        Review article: moving towards common therapeutic goals in Crohn's disease and rheumatoid arthritis.
        Aliment Pharmacol Ther. 2017; 45: 1058-1072
        • Colombel J.F.
        • Panaccione R.
        • Bossuyt P.
        • et al.
        Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial.
        Lancet. 2018; 390: 2779-2789
        • Theede K.
        • Holck S.
        • Ibsen P.
        • et al.
        Level of fecal calprotectin correlates with endoscopic and histologic inflammation and identifies patients with mucosal healing in ulcerative colitis.
        Clin Gastroenterol Hepatol. 2015; 13 (e1): 1929-1936
        • D'Haens G.
        • Ferrante M.
        • Vermeire S.
        • et al.
        Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease.
        Inflamm Bowel Dis. 2012; 18: 2218-2224
        • Schoepfer A.M.
        • Beglinger C.
        • Straumann A.
        • et al.
        Fecal calprotectin correlates more closely with the simple endoscopic score for Crohn's disease (SES-CD) than CRP, blood leukocytes, and the CDAI.
        Am J Gastroenterol. 2010; 105: 162-169