CoMiSS® was developed 7 years ago to increase the awareness of health care professionals towards the possibility that symptoms presented by infants could be related to cow’s milk. While CoMiSS was conceived mostly on theoretical concepts, data is now available from 25 clinical trials. Based on this extensive research using the tool since 2015, we aim to propose an updated CoMiSS. The evidence was reviewed, debated and discussed by 10 experts, of whom seven were part of the original group. The panel concluded that the cut-off previously proposed to indicate the likelihood that symptoms may be cow’s milk related should be lowered from ≥12 to ≥10. Data in healthy infants > 6 months are missing. Since the Brussels Infant and Toddlers Stool Scale (BITSS) was recently developed for non-toilet trained children, the Bristol Stool Scale was changed to the BITSS without changing the impact of stool characteristics on CoMiSS. Overall, CoMiSS raises awareness that symptoms might be cow’s milk related. New studies are needed to determine if the change in cut-off and other small adaptions improve its sensitivity and specificity. Data for CoMiSS is still needed in presumed healthy infants between 6 and 12 months old. There may also be regional differences in CoMiSS, in healthy infants as well as in those with cow’s milk allergy. Finally, we emphasize that CoMiSS is an awareness tool and not a diagnostic test.

Children's Hospital University of Helsinki and Helsinki University Hospital 00290 Helsinki Finland

Department Dietetics Winchester University Winchester SO23 4NR UK

Department Medicine KU Leuven 3001 Leuven Belgium

Department of Internal Medicine Geriatrics and Practical Medicine University Hospital Brno and Masaryk´s University 625 00 Brno Czech Republic

Department of Paediatrics The Medical University of Warsaw 02 014 Warsaw Poland

Department of Paediatrics University of Insubria 21100 Varese Italy

Department of Pediatrics University Hospital Brno and Masaryk's University 625 00 Brno Czech Republic

Department Paediatrics Imperial College London London SW7 2BX UK

Institute of Gastroenterology Nutrition and Liver Diseases Schneider Children's Medical Center Lea and Arieh Pickel for Pediatric Research Sackler Faculty of Medicine Tel Aviv University Tel Aviv 69978 Israel

Pediatric Allergy Unit University Hospitals of Geneva 1205 Geneva Switzerland

Pediatric Gastroenterology La Fe University Hospital Instituto de Iinvestigacion Sanitaria La FE Valencia 46026 Valencia Spain

Ramsay Group France et Clinique Marcel Sembat Paris Descartes University Boulogne Billancourt 75004 Paris France

Vrije Universiteit Brussel UZ Brussel KidZ Health Castle Laarbeeklaan 101 1090 Brussels Belgium

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Bajerova K., Salvatore S., Dupont C., Eigenmann P., Kuitunen M., Meyer R., Ribes-Koninckx C., Shamir R., Szajewska H., Vandenplas Y. The Cow’s Milk-Related Symptom Score (CoMiSS™): A Useful Awareness Tool. Nutrients. 2022;14:2059. doi: 10.3390/nu14102059. PubMed DOI PMC

Vandenplas Y., Brough H.A., Fiocchi A., Miqdady M., Munasir Z., Salvatore S., Thapar N., Venter C., Vieira M.C., Meyer R. Current Guidelines and Future Strategies for the Management of Cow’s Milk Allergy. J. Asthma Allergy. 2021;14:1243–1256. doi: 10.2147/JAA.S276992. PubMed DOI PMC

Soares-Weiser K., Takwoingi Y., Panesar S.S., Muraro A., Werfel T., Hoffmann-Sommergruber K., Roberts G., Halken S., Poulsen L., van Ree R., et al. EAACI Food Allergy and Anaphylaxis Guidelines Group. The diagnosis of food allergy: A systematic review and meta-analysis. Allergy. 2014;69:76–86. doi: 10.1111/all.12333. PubMed DOI

Vandenplas Y., Steenhout P., Planoudis Y., Grathwohl D., Althera Study Group Treating cow’s milk protein allergy: A double-blind ran-domized trial comparing two extensively hydrolysed formulas with probiotics. Acta Paediatr. 2013;102:990–998. doi: 10.1111/apa.12349. PubMed DOI

Vandenplas Y., Dupont C., Eigenmann P., Host A., Kuitunen M., Ribes-Koninckx C., Shah N., Shamir R., Staiano A., Szajewska H., et al. A workshop report on the development of the Cow’s Milk-related Symptom Score awareness tool for young children. Acta Paediatr. 2014;104:334–339. doi: 10.1111/apa.12902. PubMed DOI

Vandenplas Y., Salvatore S., Ribes-Koninckx C., Carvajal E., Szajewska H., Huysentruyt K. The Cow Milk Symptom Score (CoMiSSTM) in presumed healthy infants. PLoS ONE. 2018;13:e0200603. doi: 10.1371/journal.pone.0200603. PubMed DOI PMC

Salvatore S., Bertoni E., Bogni F., Bonaita V., Armano C., Moretti A., Baù M., Luini C., D’Auria E., Marinoni M., et al. Testing the Cow’s Milk-Related Symptom Score (CoMiSSTM) for the Response to a Cow’s Milk-Free Diet in Infants: A Prospective Study. Nutrients. 2019;11:2402. doi: 10.3390/nu11102402. PubMed DOI PMC

Vandenplas Y., Zhao Z.-Y., Mukherjee R., Dupont C., Eigenmann P., Kuitunen M., Koninckx C.R., Szajewska H., von Berg A., Bajerová K., et al. Assessment of the Cow’s Milk-related Symptom Score (CoMiSS) as a diagnostic tool for cow’s milk protein allergy: A prospective, multicentre study in China (MOSAIC study) BMJ Open. 2022;12:e056641. doi: 10.1136/bmjopen-2021-056641. PubMed DOI PMC

Huysentruyt K., Koppen I., Benninga M., Cattaert T., Cheng J., De Geyter C., Faure C., Gottrand F., Hegar B., Hojsak I., et al. The Brussels Infant and Toddler Stool Scale: A Study on Interobserver Reliability. J. Pediatr. Gastroenterol. Nutr. 2019;68:207–213. doi: 10.1097/MPG.0000000000002153. PubMed DOI

Spergel J.M. From atopic dermatitis to asthma: The atopic march. Ann. Allergy Asthma Immunol. 2010;105:99–106. doi: 10.1016/j.anai.2009.10.002. PubMed DOI

Meyer R., Fox A.T., Lozinsky A.C., Michaelis L.J., Shah N. Non-IgE-mediated gastrointestinal allergies-Do they have a place in a new model of the Allergic March. Pediatr. Allergy Immunol. 2018;30:149–158. doi: 10.1111/pai.13000. PubMed DOI

Pensabene L., Salvatore S., D’Auria E., Parisi F., Concolino D., Borrelli O., Thapar N., Staiano A., Vandenplas Y., Saps M. Cow’s Milk Protein Allergy in Infancy: A Risk Factor for Functional Gastrointestinal Disorders in Children? Nutrients. 2018;10:1716. doi: 10.3390/nu10111716. PubMed DOI PMC

Sorensen K., Meyer R., Grimshaw K.E., Cawood A.L., Acosta-Mena D., Stratton R.J. The clinical burden of cow’s milk allergy in early childhood: A retrospective cohort study. Immun. Inflamm. Dis. 2021;10:e572. doi: 10.1002/iid3.572. PubMed DOI PMC

Sladkevicius E., Nagy E., Lack G., Guest J.F. Resource implications and budget impact of managing cow milk allergy in the UK. J. Med Econ. 2009;13:119–128. doi: 10.3111/13696990903543242. PubMed DOI

Steutel N.F., Zeevenhooven J., Scarpato E., Vandenplas Y., Tabbers M.M., Staiano A., Benninga M.A. Prevalence of Functional Gastrointestinal Disorders in European Infants and Toddlers. J. Pediatr. 2020;221:107–114. doi: 10.1016/j.jpeds.2020.02.076. PubMed DOI

Bellaiche M., Ategbo S., Krumholz F., Ludwig T., Miqdady M., Abkari A., Vandenplas Y. A large-scale study to describe the prevalence, characteristics and management of functional gastrointestinal disorders in African infants. Acta Paediatr. 2020;109:2366–2373. doi: 10.1111/apa.15248. PubMed DOI PMC

Bellaiche M., Oozeer R., Gerardi-Temporel G., Faure C., Vandenplas Y. Multiple functional gastrointestinal disorders are frequent in formula-fed infants and decrease their quality of life. Acta Paediatr. 2018;107:1276–1282. doi: 10.1111/apa.14348. PubMed DOI PMC

Beser O.F., Cokugras F.C., Dogan G., Akgun O., Elevli M., Yilmazbas P., Ocal M., Bayrak N.A., Yamanel R.G.S., Bozaykut A., et al. The frequency of and factors affecting functional gastrointestinal disorders in infants that presented to tertiary care hospitals. Eur. J. Pediatr. 2021;180:2443–2452. doi: 10.1007/s00431-021-04059-2. PubMed DOI

Maoz-Segal R., Levy T., Haj-Yahia S., Offengenden I., Iancovich-Kidon M., Agmon-Levin N. Combination therapy with omalizumab and an immune-suppressive agent for resistant chronic spontaneous urticaria—A real-life experience. World Allergy Organ. J. 2020;13:100448. doi: 10.1016/j.waojou.2020.100448. PubMed DOI PMC

Fiocchi A., Knol J., Koletzko S., O’Mahony L., Papadopoulos N.G., Salminen S., Szajewska H., Nowak-Węgrzyn A. Early-Life Respiratory Infections in Infants with Cow’s Milk Allergy: An Expert Opinion on the Available Evidence and Recommendations for Future Research. Nutrients. 2021;13:3795. doi: 10.3390/nu13113795. PubMed DOI PMC

Latcham F., Merino F., Lang A., Garvey J., Thomson M.A., Walker-Smith J.A., Davies S.E., Phillips A.D., Murch S.H. A consistent pattern of minor immunodeficiency and subtle enteropathy in children with multiple food allergy. J. Pediatr. 2003;143:39–47. doi: 10.1016/S0022-3476(03)00193-8. PubMed DOI

Sinai T., Goldberg M.R., Nachshon L., Amitzur-Levy R., Yichie T., Katz Y., Monsonego-Ornan E., Elizur A. Reduced Final Height and Inadequate Nutritional Intake in Cow’s Milk-Allergic Young Adults. J. Allergy Clin. Immunol. Pract. 2018;7:509–515. doi: 10.1016/j.jaip.2018.11.038. PubMed DOI

Oldbury S., Adams K. The impact of infant crying on the parent-infant relationship. Community Pract. 2015;88:29–34. PubMed

Vandenplas Y., Hachimi-Idrissi S., Casteels A., Mahler T., Loeb H. A clinical trial with an “anti-regurgitation” formula. Eur. J. Pediatr. 1994;153:419–423. doi: 10.1007/bf01983405. PubMed DOI

Rosen R., Vandenplas Y., Singendonk M., Cabana M., DiLorenzo C., Gottrand F., Gupta S., Langendam M., Staiano A., Thapar N., et al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J. Pediatr. Gastroenterol. Nutr. 2018;66:516–554. doi: 10.1097/MPG.0000000000001889. PubMed DOI PMC

Leonard S.A., Miceli Sopo S., Baker M.G., Fiocchi A., Wood R.A., Nowak-Węgrzyn A. Management of acute food pro-tein-induced enterocolitis syndrome emergencies at home and in a medical facility. Ann. Allergy Asthma Immunol. 2021;126:482–488.e1. doi: 10.1016/j.anai.2021.01.020. PubMed DOI

Heaton K.W., Radvan J., Cripps H., Mountford R.A., Braddon F.E., Hughes A.O. Defecation frequency and timing, and stool form in the general population: A prospective study. Gut. 1992;33:818–824. doi: 10.1136/gut.33.6.818. PubMed DOI PMC

Ghanma A., Puttemans K., Deneyer M., Benninga M., Vandenplas Y. Amsterdam infant stool scale is more useful for assessing children who have not been toilet trained than Bristol stool scale. Acta Paediatr. 2013;103:e91–e92. doi: 10.1111/apa.12422. PubMed DOI

Chumpitazi B.P., Lane M.M., Czyzewski D.I., Weidler E.M., Swank P.R., Shulman R.J. Creation and Initial Evaluation of a Stool Form Scale for Children. J. Pediatr. 2010;157:594–597. doi: 10.1016/j.jpeds.2010.04.040. PubMed DOI PMC

Wegh C.A., Hermes G.D., Schoterman M.H., Vaughan E.E., Smidt H., Belzer C., Benninga M.A. The modified bristol stool form scale: A reliable and valid tool to score stool consistency in Dutch (non)toilet-trained toddlers. J. Pediatr. Gastroenterol. Nutr. 2021;73:210–216. doi: 10.1097/MPG.0000000000003186. PubMed DOI

Lane M.M., Czyzewski D.I., Chumpitazi B.P., Shulman R.J. Reliability and Validity of a Modified Bristol Stool Form Scale for Children. J. Pediatr. 2011;159:437–441.e1. doi: 10.1016/j.jpeds.2011.03.002. PubMed DOI PMC

Bajerova K., Ribes-Koninckx C., Salvatore S., Vandenplas Y. Changing the stool scoring item in the Cow’s Milk-Related Symptom Score (CoMiSS™): Does it influence the cut-off for cow’s milk allergy risk?; Proceedings of the European Academy of Allergy and Clinical Immunology; Prague, Czech Republic. 1–3 July 2022.

Nowak-Węgrzyn A. Food protein-induced enterocolitis syndrome and allergic proctocolitis. Allergy Asthma Proc. 2015;36:172–184. doi: 10.2500/aap.2015.36.3811. PubMed DOI PMC

Mennini M., Fiocchi A.G., Cafarotti A., Montesano M., Mauro A., Villa M.P., Di Nardo G. Food protein-induced allergic proctocolitis in infants: Literature review and proposal of a management protocol. World Allergy Organ. J. 2020;13:100471. doi: 10.1016/j.waojou.2020.100471. PubMed DOI PMC

Elizur A., Cohen M., Goldberg M.R., Rajuan N., Cohen A., Leshno M., Katz Y. Cow’s milk associated rectal bleeding: A population based prospective study. Pediatr. Allergy Immunol. 2012;23:765–769. doi: 10.1111/pai.12009. PubMed DOI

Jirapinyo P., Densupsoontorn N., Kangwanpornsiri C. Anal fissures in infants may be a pathognomonic sign of infants with cow’s milk allergy. J. Med. Assoc. Thail. 2013;96:786–789. PubMed

Sopo S.M., Monaco S., Bersani G., Romano A., Fantacci C. Proposal for management of the infant with suspected food protein-induced allergic proctocolitis. Pediatr. Allergy Immunol. 2017;29:215–218. doi: 10.1111/pai.12844. PubMed DOI

Mehr S., Campbell D.E. Food protein-induced enterocolitis syndrome: Guidelines summary and practice recommendations. Med. J. Aust. 2019;210:94–99. doi: 10.5694/mja2.12071. PubMed DOI

Caubet J.C., Ford L.S., Sickles L., Järvinen K.M., Sicherer S.H., Sampson H.A., Nowak-Węgrzyn A. Clinical features and resolution of food protein–induced enterocolitis syndrome: 10-year experience. J. Allergy Clin. Immunol. 2014;134:382–389.e4. doi: 10.1016/j.jaci.2014.04.008. PubMed DOI

Hill D.J., Hosking C.S. Food allergy and atopic dermatitis in infancy: An epidemiologic study. Pediatr. Allergy Immunol. 2004;15:421–427. doi: 10.1111/j.1399-3038.2004.00178.x. PubMed DOI

Fiocchi A., Brozek J., Schünemann H., Bahna S.L., von Berg A., Beyer K., Bozzola M., Bradsher J., Compalati E., Ebisawa M., et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guidelines. World Allergy Organ. J. 2010;3:57–161. doi: 10.1097/WOX.0b013e3181defeb9. PubMed DOI PMC

Alford S.H., Zoratti E., Peterson E.L., Maliarik M., Ownby D.R., Johnson C.C. Parental history of atopic disease: Disease pattern and risk of pediatric atopy in offspring. J. Allergy Clin. Immunol. 2004;114:1046–1050. doi: 10.1016/j.jaci.2004.08.036. PubMed DOI

Koplin J.J., Allen K.J., Gurrin L.C., Peters R.L., Lowe A.J., Tan H.-T.T., Dharmage S.C. The Impact of Family History of Allergy on Risk of Food Allergy: A Population-Based Study of Infants. Int. J. Environ. Res. Public Health. 2013;10:5364–5377. doi: 10.3390/ijerph10115364. PubMed DOI PMC

Turner P.J., Feeney M., Meyer R., Perkin M., Fox A.T. Implementing primary prevention of food allergy in infants: New BSACI guidance published. Clin. Exp. Allergy. 2018;48:912–915. doi: 10.1111/cea.13218. PubMed DOI

Turner P., Worm M., Ansotegui I.J., El-Gamal Y., Rivas M.F., Fineman S., Geller M., Gonzalez-Estrada A., Greenberger P.A., Tanno L., et al. Time to revisit the definition and clinical criteria for anaphylaxis? World Allergy Organ. J. 2019;12:100066. doi: 10.1016/j.waojou.2019.100066. PubMed DOI PMC

Vandenplas Y., Carvajal E., Peeters S., Balduck N., Jaddioui Y., Ribes-Koninckx C., Huysentruyt K. The Cow’s Milk-Related Symptom Score (CoMiSSTM): Health Care Professional and Parent and Day-to-Day Variability. Nutrients. 2020;12:438. doi: 10.3390/nu12020438. PubMed DOI PMC

Vieira M.C., Morais M.B., Spolidoro J.V., Toporovski M.S., Cardoso A.L., Araujo G.T., Nudelman V., Fonseca M.C. A survey on clinical presentation and nutritional status of infants with suspected cow’ milk allergy. BMC Pediatr. 2010;10:25. doi: 10.1186/1471-2431-10-25. PubMed DOI PMC

Tuokkola J., Luukkainen P., Nevalainen J., Ahonen S., Toppari J., Ilonen J., Veijola R., Knip M., Virtanen S., Kaila M. Eliminating cows’ milk, but not wheat, barley or rye, increases the risk of growth deceleration and nutritional inadequacies. Acta Paediatr. 2017;106:1142–1149. doi: 10.1111/apa.13846. PubMed DOI

Isolauri E., Sütas Y., Salo M., Isosomppi R., Kaila M. Elimination diet in cow’s milk allergy: Risk for impaired growth in young children. J. Pediatr. 1998;132:1004–1009. doi: 10.1016/S0022-3476(98)70399-3. PubMed DOI

Nachshon L., Goldberg M.R., Schwartz N., Sinai T., Amitzur-Levy R., Elizur A., Eisenberg E., Katz Y. Decreased bone mineral density in young adult IgE-mediated cow’s milk–allergic patients. J. Allergy Clin. Immunol. 2014;134:1108–1113.e3. doi: 10.1016/j.jaci.2014.06.026. PubMed DOI

Giovannini M., D’Auria E., Caffarelli C., Verduci E., Barberi S., Indinnimeo L., Iacono I.D., Martelli A., Riva E., Bernardini R. Nutritional management and follow up of infants and children with food allergy: Italian Society of Pediatric Nutrition/Italian Society of Pediatric Allergy and Immunology Task Force Position Statement. Ital. J. Pediatr. 2014;40:1. doi: 10.1186/1824-7288-40-1. PubMed DOI PMC

Venter C., Mazzocchi A., Maslin K., Agostoni C. Impact of elimination diets on nutrition and growth in children with multiple food allergies. Curr. Opin. Allergy Clin. Immunol. 2017;17:220–226. doi: 10.1097/ACI.0000000000000358. PubMed DOI

Koletzko S., Niggemann B., Arato A., Dias J.A., Heuschkel R., Husby S., Mearin M.L., Papadopoulou A., Ruemmele F.M., Staiano A., et al. Diagnostic Approach and Management of Cow’s-Milk Protein Allergy in Infants and Children: Espghan gi committee practical guidelines. J. Pediatr. Gastroenterol. Nutr. 2012;55:221–229. doi: 10.1097/MPG.0b013e31825c9482. PubMed DOI

Ludwig T., Oukid I., Wong J., Ting S., Huysentruyt K., Roy P., Foussat A.C., Vandenplas Y. Machine Learning Supports Automated Digital Image Scoring of Stool Consistency in Diapers. J. Pediatr. Gastroenterol. Nutr. 2021;72:255–261. doi: 10.1097/MPG.0000000000003007. PubMed DOI PMC

Evaluating the Need for Pre-CoMiSS™, a Parent-Specific Cow's Milk-Related Symptom Score: A Qualitative Study

The evolution of Cow's Milk-related Symptom Score (CoMiSS™) in presumed healthy infants

Cow's Milk-related Symptom Score (CoMiSS) values in presumed healthy European infants aged 6-12 months: a cross-sectional study

Cow's Milk-Related Symptom Score (CoMiSS): From Bristol to Brussels Stool Scale