Cow’s milk protein allergy in children: a contemporary approach to diagnosis and management (literature review)
DOI:
https://doi.org/10.15574/SP.2025.8(152).7986Keywords:
cow’s milk protein allergy, IgE-mediated reaction, non-IgE-mediated reaction, diagnosis, treatmentAbstract
Cow’s milk protein allergy (CMPA) is an allergic reaction to the proteins found in cow’s milk. Diagnosing this condition can be challenging, as it is primarily based on clinical history and physical examination. It is important for physicians to differentiate between milk allergy and milk intolerance, as the approaches to diagnosis and treatment of these two conditions differ.
Aim - to summarize the literature on the epidemiology, clinical manifestations, diagnostic methods, and treatment of cow’s milk allergy.
Immune-mediated adverse food reactions are classified as IgE-mediated, non-IgE-mediated (with the latter being most commonly responsible for CMPA), and mixed forms (involving both IgE- and non-IgE-mediated mechanisms). CMPA should be suspected in children who develop immediate symptoms such as anaphylaxis, laryngeal edema, acute urticaria or angioedema, as well as acute asthma with severe respiratory distress. Delayed reactions may include blood in stools, atopic dermatitis, chronic diarrhea, iron deficiency anemia, gastroesophageal reflux disease, chronic vomiting, colic, constipation, failure to thrive, food refusal, enterocolitis syndrome, enteropathy with hypoalbuminemia, and eosinophilic esophagogastroenteritis. The Cow’s Milk-related Symptom Score (CoMiSS™) is a modern clinical screening tool developed to aid healthcare professionals in the early diagnosis of CMPA and to raise awareness about this condition. The use of food antigen-specific IgG testing panels should be avoided, as they are not evidence-based and may lead to overdiagnosis of presumed food intolerance.
Conclusions. CMPA should not be confused with cow’s milk intolerance, which is relatively rare in infants. For breastfed infants, formula supplementation during the first 24 hours of life is not recommended, as it increases the risk of developing CMPA. Mothers and healthcare providers should be aware of the benefits of exclusive breastfeeding and be supported with appropriate resources to avoid unnecessary formula supplementation and reduce the risk of CMPA.
The authors declare no conflict of interest.
References
Bajerova K, Hrabcova K, Vandenplas Y. (2024, Oct). The evolution of Cow's Milk-related Symptom Score (CoMiSS™) in presumed healthy infants. Eur J Pediatr. 183(10): 4329-4335. https://doi.org/10.1007/s00431-024-05693-2; PMid:39078481 PMCid:PMC11413180
Bajerova K, Salvatore S, Dupont C, Eigenmann P, Kuitunen M, Meyer R et al. (2022, May 14). The Cow's Milk-Related Symptom Score (CoMiSS™): A Useful Awareness Tool. Nutrients. 14(10): 2059. https://doi.org/10.3390/nu14102059; PMid:35631201 PMCid:PMC9146599
Bajerova K, Salvatore S, Dupont C, Kuitunen M, Meyer R, Ribes-Koninckx C et al. (2023, Nov 1). Cow's Milk-Related Symptom Score (CoMiSS): From Bristol to Brussels Stool Scale. J Pediatr Gastroenterol Nutr. 77(5): 618-622. https://doi.org/10.1097/MPG.0000000000003932; PMid:37668589 PMCid:PMC10583930
Baldo F, Bevacqua M, Corrado D et al. (2020). FPIES in exclusively breastfed infants: Two case reports and review of the literature. Ital J Pediatr. 46(1): 144. https://doi.org/10.1186/s13052-020-00910-8; PMid:33023612 PMCid:PMC7539526
Barni S, Liccioli G, Sarti L, Giovannini M, Novembre E, Mori F. (2020, Mar 4). Immunoglobulin E (IgE)-Mediated Food Allergy in Children: Epidemiology, Pathogenesis, Diagnosis, Prevention, and Management. Medicina (Kaunas). 56(3): 111. https://doi.org/10.3390/medicina56030111; PMid:32143431 PMCid:PMC7142605
Bartuzi Z, Cocco RR, Muraro A, Nowak-Węgrzyn A. (2017, Jul). Contribution of Molecular Allergen Analysis in Diagnosis of Milk Allergy. Curr Allergy Asthma Rep. 17(7): 46. https://doi.org/10.1007/s11882-017-0716-z; PMid:28597347
Boyce JA, Assa'ad A, Burks AW, Jones SM, Sampson HA, Wood RA et al. (2010, Dec). NIAID-Sponsored Expert Panel. Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report. J Allergy Clin Immunol. 126(6): 1105-1118. https://doi.org/10.1016/j.jaci.2010.10.008; PMid:21134568 PMCid:PMC4241958
Buyuktiryaki B, Soyer O, Bingol G, Can C, Nacaroglu HT, Bingol A et al. (2024, Dec 6). Milk ladder: Who? When? How? Where? with the lowest risk of reaction. Front Allergy. 5: 1516774. doi: 10.3389/falgy.2024.1516774. Erratum in: Front Allergy. 2025 Mar 14; 6: 1576302. https://doi.org/10.3389/falgy.2025.1576302; PMid:40161855 PMCid:PMC11950728
Caffarelli C, Santamaria F, Di Mauro D, Mastrorilli C, Montella S, Tchana B et al. (2018, Jul 17). Advances in pediatrics in 2017: current practices and challenges in allergy, endocrinology, gastroenterology, genetics, immunology, infectious diseases, neonatology, nephrology, neurology, pulmonology from the perspective of Italian Journal of Pediatrics. Ital J Pediatr. 44(1): 82. https://doi.org/10.1186/s13052-018-0524-7; PMid:30016966 PMCid:PMC6050676
Cuomo B, Indirli GC, Bianchi A, Arasi S, Caimmi D, Dondi A et al. (2017, Oct 12). Specific IgE and skin prick tests to diagnose allergy to fresh and baked cow's milk according to age: a systematic review. Ital J Pediatr. 43(1): 93. https://doi.org/10.1186/s13052-017-0410-8; PMid:29025431 PMCid:PMC5639767
Darma A, Sumitro KR, Jo J, Sitorus N. (2024, Jan 31). Lactose Intolerance versus Cow's Milk Allergy in Infants: A Clinical Dilemma. Nutrients. 16(3): 414. https://doi.org/10.3390/nu16030414; PMid:38337698 PMCid:PMC10856892
De Greef E, Hauser B, Devreker T, Veereman-Wauters G, Vandenplas Y. (2012, Feb). Diagnosis and management of cow's milk protein allergy in infants. World J Pediatr. 8(1): 19-24. https://doi.org/10.1007/s12519-012-0332-x; PMid:22282379
Florquin M, Eerdekens A. (2023, Oct). What is Known About Cow's Milk Protein Allergy in Preterm Infants? Breastfeed Med. 18(10): 767-778. https://doi.org/10.1089/bfm.2023.0122; PMid:37856666
Giannetti A, Cipriani F, Indio V, Gallucci M, Caffarelli C, Ricci G. (2019, Aug 10). Influence of Atopic Dermatitis on Cow's Milk Allergy in Children. Medicina (Kaunas). 55(8): 460. https://doi.org/10.3390/medicina55080460; PMid:31405131 PMCid:PMC6723735
Hicks A, Fleischer D, Venter C. (2024, Feb 28). The future of cow's milk allergy - milk ladders in IgE-mediated food allergy. Front Nutr. 11: 1371772. doi: 10.3389/fnut.2024.1371772. Erratum in: Front Nutr. 2025 Apr 01; 12: 1521516. https://doi.org/10.3389/fnut.2025.1521516; PMid:40236642 PMCid:PMC11997381
Jankiewicz M, Ahmed F, Bajerova K, Carvajal Roca ME, Dupont C, Huysentruyt K et al. (2024, Feb). Cow's Milk-related Symptom Score (CoMiSS) values in presumed healthy European infants aged 6-12 months: a cross-sectional study. Eur J Pediatr. 183(2): 707-713. https://doi.org/10.1007/s00431-023-05334-0; PMid:37973640 PMCid:PMC10912251
Kansu A, Yüce A, Dalgıç B, Şekerel BE, Çullu-Çokuğraş F, Çokuğraş H. (2016). Consensus statement on diagnosis, treatment and follow-up of cow's milk protein allergy among infants and children in Turkey. Turk J Pediatr. 58(1): 1-11. https://doi.org/10.24953/turkjped.2016.01.001; PMid:27922230
Katz Y, Goldberg MR. (2014). Natural history of food protein-induced enterocolitis syndrome. Curr Opin Allergy Clin Immunol. 14(3): 229-239. https://doi.org/10.1097/ACI.0000000000000053; PMid:24686278 PMCid:PMC4011630
Kelly E, DunnGalvin G, Murphy BP, O'B Hourihane J. (2019, Dec). Formula supplementation remains a risk for cow's milk allergy in breast-fed infants. Pediatr Allergy Immunol. 30(8): 810-816. https://doi.org/10.1111/pai.13108; PMid:31297890
Koletzko S, Niggemann B, Arato A, Dias JA, Heuschkel R, Husby S et al. (2012, Aug). European Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Diagnostic approach and management of cow's-milk protein allergy in infants and children: ESPGHAN GI Committee practical guidelines. J Pediatr Gastroenterol Nutr. 55(2): 221-229. https://doi.org/10.1097/MPG.0b013e31825c9482; PMid:22569527
Labrosse R, Graham F, Caubet JC. (2020). Non-IgE-mediated gastrointestinal food allergies in children: An update. Nutrients. 12(7): 2086. https://doi.org/10.3390/nu12072086; PMid:32674427 PMCid:PMC7400851
Lifschitz C, Szajewska H. (2015, Feb). Cow's milk allergy: evidence-based diagnosis and management for the practitioner. Eur J Pediatr. 174(2): 141-150. https://doi.org/10.1007/s00431-014-2422-3; PMid:25257836
Luyt D, Ball H, Makwana N, Green MR, Bravin K et al. (2014) Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). BSACI guideline for the diagnosis and management of cow's milk allergy. Clin Exp Allergy. 44(5): 642-672. https://doi.org/10.1111/cea.12302; PMid:24588904
Martorell A, Plaza AM, Boné J, Nevot S, García Ara MC, Echeverria L et al. (2006, Mar-Apr). Cow's milk protein allergy. A multi-centre study: clinical and epidemiological aspects. Allergol Immunopathol (Madr). 34(2): 46-53. https://doi.org/10.1157/13086746; PMid:16606545
Myszkowska D, Zapata B, Bulanda M, Czarnobilska E. (2021). Non-IgE mediated hypersensitivity to food products or food intolerance - Problems of appropriate diagnostics. Medicina (Kaunas). 57(11): 1245. https://doi.org/10.3390/medicina57111245; PMid:34833463 PMCid:PMC8625578
Nowak-Węgrzyn A, Chehade M, Groetch ME et al. (2017). International consensus guidelines for the diagnosis and management of food protein-induced enterocolitis syndrome: Executive summary-Workgroup report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 139(4): 1111-26.e4. https://doi.org/10.1016/j.jaci.2016.12.966; PMid:28167094
Ogata M, Kido J, Nakamura K. (2021, Oct 15). Oral Immunotherapy for Children with Cow's Milk Allergy. Pathogens. 10(10): 1328. https://doi.org/10.3390/pathogens10101328; PMid:34684278 PMCid:PMC8539286
Oranje AP, Wolkerstorfer A, de Waard-van der Spek FB. (2002, Dec). Natural course of cow's milk allergy in childhood atopic eczema/dermatitis syndrome. Ann Allergy Asthma Immunol. 89; 6 Suppl 1: 52-55. https://doi.org/10.1016/S1081-1206(10)62123-0; PMid:12487205
Pensabene L, Salvatore S, D'Auria E, Parisi F, Concolino D, Borrelli O et al. (2018, Nov 9). Cow's Milk Protein Allergy in Infancy: A Risk Factor for Functional Gastrointestinal Disorders in Children? Nutrients. 10(11): 1716. https://doi.org/10.3390/nu10111716; PMid:30423934 PMCid:PMC6265683
Salvatore S, Agosti M, Baldassarre ME, D'Auria E, Pensabene L et al. (2021, Jan 21). Cow's Milk Allergy or Gastroesophageal Reflux Disease-Can We Solve the Dilemma in Infants? Nutrients. 13(2): 297. https://doi.org/10.3390/nu13020297; PMid:33494153 PMCid:PMC7909757
Schoemaker AA, Sprikkelman AB, Grimshaw KE, Roberts G, Grabenhenrich L, Rosenfeld L et al. (2015, Aug). Incidence and natural history of challenge-proven cow's milk allergy in European children - EuroPrevall birth cohort. Allergy. 70(8): 963-972. https://doi.org/10.1111/all.12630; PMid:25864712
Sorensen K, Meyer R, Grimshaw KE, Cawood AL, Acosta-Mena D, Stratton RJ. (2022, Mar). The clinical burden of cow's milk allergy in early childhood: A retrospective cohort study. Immun Inflamm Dis. 10(3): e572. https://doi.org/10.1002/iid3.572; PMid:34873874 PMCid:PMC8926503
Vandenplas Y, Bajerova K, Dupont C, Eigenmann P, Kuitunen M, Meyer R et al. (2022, Jun 28). The Cow's Milk Related Symptom Score: The 2022 Update. Nutrients. 14(13): 2682. https://doi.org/10.3390/nu14132682; PMid:35807862 PMCid:PMC9268587
Vandenplas Y, Bajerová K, Dupont C, Kuitunen M, Meyer R, Nowak-Wegrzyn A et al. (2025, Apr 30). Evaluating the Need for Pre-CoMiSS™, a Parent-Specific Cow's Milk-Related Symptom Score: A Qualitative Study. Nutrients. 17(9): 1563. https://doi.org/10.3390/nu17091563; PMid:40362872 PMCid:PMC12073529
Vandenplas Y, Belohlavkova S, Enninger A, Frühauf P, Makwana N, Järvi A. (2021, Aug 30). How Are Infants Suspected to Have Cow's Milk Allergy Managed? A Real World Study Report. Nutrients. 13(9): 3027. https://doi.org/10.3390/nu13093027; PMid:34578905 PMCid:PMC8464701
Vandenplas Y, Meyer R, Nowak-Wegrzyn A, Salvatore S, Venter C, Vieira MC. (2023, Nov 13). The Remaining Challenge to Diagnose and Manage Cow's Milk Allergy: An Opinion Paper to Daily Clinical Practice. Nutrients. 15(22): 4762. https://doi.org/10.3390/nu15224762; PMid:38004156 PMCid:PMC10675216
Votto M, De Filippo M, Caimmi S, Indolfi C, Raffaele A, Tosca MA et al. (2023, Sep 28). Practical Update on Pediatric Eosinophilic Esophagitis. Children (Basel). 10(10): 1620. https://doi.org/10.3390/children10101620; PMid:37892285 PMCid:PMC10605219
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Modern pediatrics. Ukraine

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The policy of the Journal “MODERN PEDIATRICS. UKRAINE” is compatible with the vast majority of funders' of open access and self-archiving policies. The journal provides immediate open access route being convinced that everyone – not only scientists - can benefit from research results, and publishes articles exclusively under open access distribution, with a Creative Commons Attribution-Noncommercial 4.0 international license (СС BY-NC).
Authors transfer the copyright to the Journal “MODERN PEDIATRICS. UKRAINE” when the manuscript is accepted for publication. Authors declare that this manuscript has not been published nor is under simultaneous consideration for publication elsewhere. After publication, the articles become freely available on-line to the public.
Readers have the right to use, distribute, and reproduce articles in any medium, provided the articles and the journal are properly cited.
The use of published materials for commercial purposes is strongly prohibited.