Objective: There is still an unmet need for a reliable and straightforward biomarker to diagnose and monitor cow’s milk protein allergy (CMPA). Fecal calprotectin (FC) has been reported as a biomarker for CMPA. Therefore, the meta-analysis aimed to evaluate the value of FC in the diagnosis and monitoring of CMPA. Methods: PubMed, EMBASE, and the Cochrane Library up to April 2022 were searched for relevant studies. Pooled standardized mean difference (SMD) and 95% confidence intervals (CIs) were determined using the forest plot. Heterogeneity was used to determine the fixed or random-effect model. Results: Twelve studies including 310 patients and 217 controls were available for the meta-analysis. The FC levels in children with CMPA were significantly higher than in healthy control (SMD = 1.15; 95% CI: 0.38–1.91). After elimination diet treatment, FC levels were reduced considerably with the pooled SMD of 0.87 (95% CI: 0.48–1.26). Conclusion: The results indicated that FC could be a simple and reliable biomarker for diagnosing CMPA, especially in non-IgE-mediated CMPA infants. Besides, calprotectin was also potential for predicting therapy response of CMPA.

Gupta RS, Dyer AA, Jain N, Greenhawt MJ. Childhood food allergies: current diagnosis, treatment, and management strategies.
Mayo Clin Proc
. 2013;88(5):512–26.
Wang W, Zhang XH, Zhu L, Liu YX. Investigation of allergic sensitization pattern in 4,203 children in Northern China.
Int Arch Allergy Immunol
. 2021;182(5):455–8.
Valenta R, Hochwallner H, Linhart B, Pahr S. Food allergies: the basics.
. 2015;148(6):1120–31.e4.
Khanna N, Patel K. FPIES: reviewing the management of food protein-induced enterocolitis syndrome.
Case Rep Pediatr
. 2016;2016:1621827.
Stríz I, Trebichavský I. Calprotectin: a pleiotropic molecule in acute and chronic inflammation.
Physiol Res
. 2004;53(3):245–53.
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(2):171–7.
Baldassarre ME, Laforgia N, Fanelli M, Laneve A, Grosso R, Lifschitz C. Lactobacillus GG improves recovery in infants with blood in the stools and presumptive allergic colitis compared with extensively hydrolyzed formula alone.
J Pediatr
. 2010;156(3):397–401.
Beşer OF, Sancak S, Erkan T, Kutlu T, Cokuğraş H, Cokuğraş FÇ. Can fecal calprotectin level be used as a markers of inflammation in the diagnosis and follow-up of cow’s milk protein allergy?
Allergy Asthma Immunol Res
. 2014;6(1):33–8.
Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range.
BMC Med Res Methodol
. 2014;14:135.
Roca M, Donat E, Rodriguez Varela A, Carvajal E, Cano F, Armisen A, et al. Fecal calprotectin and eosinophil-derived neurotoxin in children with non-IgE-mediated cow’s milk protein allergy.
J Clin Med
. 2021;10(8):1595.
Merras-Salmio L, Kolho KL, Pelkonen AS, Kuitunen M, Mäkelä MJ, Savilahti E. Markers of gut mucosal inflammation and cow’s milk specific immunoglobulins in non-IgE cow’s milk allergy.
Clin Transl Allergy
. 2014;4(1):8.
Trillo Belizón C, Ortega Páez E, Medina Claros AF, Rodríguez Sánchez I, Reina González AM, Vera Medialdea R, et al. [Faecal calprotectin as an aid to the diagnosis of non-IgE mediated cow’s milk protein allergy].
Anales de pediatria
. 2016;84(6):318–23.
Winberg A, Nagaeva O, Nagaev I, Lundell C, Arencibia I, Mincheva-Nilsson L, et al. Dynamics of cytokine mRNA expression and fecal biomarkers in school-children undergoing a double-blind placebo-controlled food challenge series.
. 2016;88:259–66.
Ataee P, Zoghali M, Nikkhoo B, Ghaderi E, Mansouri M, Nasiri R, et al. Diagnostic value of fecal calprotectin in response to mother’s diet in breast-fed infants with cow’s milk allergy colitis.
Iranian J Pediatr
. 2018;28(4):e66172.
Díaz M, Guadamuro L, Espinosa-Martos I, Mancabelli L, Jiménez S, Molinos-Norniella C, et al. Microbiota and derived parameters in fecal samples of infants with non-IgE cow’s milk protein allergy under a restricted diet.
. 2018;10(10):E1481.
Ambroszkiewicz J, Gajewska J, Chełchowska M, Rowicka G. Assessment of inflammatory markers in children with cow’s milk allergy treated with a milk-free diet.
. 2021;13(4):1057.
Qiu L, Wang J, Ren F, Shen L, Li F. Can fecal calprotectin levels be used to monitor infant milk protein allergies?
Allergy Asthma Clin Immunol
. 2021;17(1):132.
Prikhodchenko NG, Shumatova TA, Nee AN, Katenkova EU, Zernova ES, Grigoryan LA. Noninvasive Marker of the Intestinal Epithelial Barrier State in Infants with Food Protein-Induced Enteropathy.
Res J Pharm Biol Chem Sci
. 2018;9(5):625–628.
Lendvai-Emmert D, Emmert V, Fusz K, Prémusz V, Boncz I, Tóth GP. Quantitative assay of fecal calprotectin in children with cow’s milk protein allergy.
Value Health
. 2018;21:S128.
Røseth AG, Fagerhol MK, Aadland E, Schjønsby H. Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study.
Scand J Gastroenterol
. 1992;27(9):793–8.
Xiong LJ, Xie XL, Li Y, Deng XZ. Current status of fecal calprotectin as a diagnostic or monitoring biomarker for cow’s milk protein allergy in children: a scoping review.
World J Pediatr
. 2021;17(1):63–70.
Calvani M, Anania C, Cuomo B, D'Auria E, Decimo F, Indirli GC, et al. Non-IgE- or mixed IgE/non-IgE-Mediated gastrointestinal food allergies in the first years of life: old and new tools for diagnosis.
. 2021;13(1):226.
Galip N, Yuruker O, Babayigit A. Characteristics of allergic proctocolitis in early infancy; accuracy of diagnostic tools and factors related to tolerance development.
Asian Pac J Allergy Immunol
. 2021. Online ahead of print.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.