Real-life management of gastrointestinal cow’s milk protein allergy in Brazilian infants
Main Article Content
Keywords
access to essential medicines and health technologies, diagnostic techniques and procedures, elimination diet, professional practice
Abstract
Objective: To evaluate physicians’ management of non-immunoglobulin E-mediated gastrointestinal cow’s milk protein allergy (non-IgE-GI-CMPA) in Brazilian infants.
Methods: A total of 447 physicians from all the regions of Brazil answered an online questionnaire concerning their management of formula-fed infants with mild-to-moderate (Case 1) or severe (Case 2) clinical manifestations of non-IgE-GI-CMPA.
Results: In total, 95.3% and 86.0% of the interviewed physicians in cases 1 and 2 prescribed a cow’s milk elimination diet (p < 0.001). In the initial management, the prescription rates of formulas based on extensively hydrolyzed protein and amino acid were 81.7% and 14.6% for Case 1 and 32.7% and 65.4% for Case 2 (p < 0.001); the percentages of answers for prescriptions of drugs or probiotics were 8.3% and 12.1% in cases 1 and 2 (p < 0.001); and requests for laboratory tests were 12.3% and 37.7 % (p = 0.016). The oral food challenge (OFC) test for the diagnosis of non-IgE-GI-CMPA was indicated by 55.1% and 42.7% of the physicians in cases 1 and 2 (p < 0.001). The OFC test was chosen to assess tolerance development by 92% of the interviewees. Performing the diagnostic OFC (D-OFC) test was positively associated with having board certification in pediatric gastroenterology and < 20 years of professional experience and negatively associated with using baked foods as a protein source in the oral tolerance OFC test.
Conclusions: Most interviewees followed the guidelines regarding prescribing an elimination diet; however, many should include the OFC test in diagnosing infants with non-IgE-GI-CMPA. Not performing the D-OFC may have negative consequences on patients and on the public healthcare system.
References
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2 Toca MC, Morais MB, Vásquez-Frias R, Becker-Cuevas DJ, Boggio-Marzet CG, Delgado-Carbajal L, et al. Consensus on the diagnosis and treatment of cow milk protein allergy by the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Rev Gastroenterol Mex (Engl Ed). 2022;87(2):235–50. 10.1016/j.rgmxen.2022.01.002
3 Vandenplas Y, Broekaert I, Domellöf M, Indrio F, Lapillonne A, Pienar C, et al. An ESPGHAN position paper on the diagnosis, management, and prevention of cow’s milk allergy. J Pediatr Gastroenterol Nutr. 2024 Feb;78(2):386-413. 10.1097/MPG.0000000000003897
4 Meyer R, Venter C, Bognanni A, Szajewska H, Shamir R, Nowak-Wegrzyn A, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guideline update–VII–Milk elimination and reintroduction in the diagnostic process of cow’s milk allergy. World Allergy Organ J. 2023;16(7):100785. 10.1016/j.waojou.2023.100785
5 Sissoko NDN, Chen W, Wang C, Wu Y, Zheng X, Dong X, et al. Associations between functional constipation and non-IgE-mediated food allergy in infants and children. Allergol Immunopathol (Madr). 2023;51(3):163–73. 10.15586/aei.v51i3.738. PMid: 37169574
6 Morais MB, Toporovski MS, Tofoli MHC, Barros KV, Silva LR, Ferreira CHT. Prevalence of functional gastrointestinal disorders in Brazilian infants seen in private pediatric practices and their associated factors. J Pediatr Gastroenterol Nutr. 2022;75(1):17–23. 10.1097/MPG.0000000000003469
7 Lins MG, Horowitz MR, Silva GAP, Motta ME. Oral food challenge test to confirm the diagnosis of cow’s milk allergy. J Pediatr (Rio J). 2010;86:285–9. 10.2223/jped.2011
8 Medeiros LC, Speridião PG, Sdepanian VL, Fagundes-Neto U, Morais MB. Nutrient intake and nutritional status of children following a diet free from cow’s milk and cow’s milk by-products. J Pediatr (Rio J). 2004;80:363–70. pubmed.ncbi.nlm.nih.gov/15505731/
9 Vieira MC, Morais MB, Spolidoro JV, Toporovski MS, Cardoso AL, Araujo GT, et al. A survey on clinical presentation and nutritional status of infants with suspected cow’ milk allergy. BMC Pediatr. 2010;10:25. 10.1186/1471-2431-10-25
10 Meyer R. Nutritional disorders resulting from food allergy in children. Pediatr Allergy Immunol. 2018;29:689–704. 10.1111/pai.12960
11 Augusto EO, Bonucci VG, Cardoso RV, Morais MB. Complementary feeding and nutritional status of infants on cow’s milk proteins elimination diet. Rev Paul Pediatr. 2022;40:e20200429. 10.1590/1984-0462/2022/40/2020429IN
12 Rodrigues VCC, Speridião PGL, Sanudo A, Morais MB. Feeding difficulties in children fed a cows’ milk elimination diet. Br J Nutr. 2022;128(6):1190–9. 10.1017/S0007114521004165
13 Frizzo J, Rodrigues VCC, Speridião PGL, Morais MB. Evaluation of the complementary feeding practices, dietary intake, and nutritional status of infants on a cow’s milk protein elimination diet. J Pediatr (Rio J). 2022;98:256–63. 10.1016/j.jped.2021.06.005
14 Jardim-Botelho A, Martins TG, Motta-Franco J, Meyer R, Fontes Vieira SC, Protásio BF, et al. Growth and nutritional biomarkers in Brazilian infants with cow’s milk allergy at diagnosis and 18-month follow-up: A prospective cohort study. Pediatr Gastroenterol Hepatol Nutr. 2023;26(6):355–69. 10.5223/pghn.2023.26.6.355
15 Fakih-Botero I, Cerchiaro-Mejia MC, Rusinque MJ, Palacios-Ariza MA, Plata-Garcia CE, Peña-Hernández S. Out-of-pocket expenses and parent reported quality of life in children with cow’s milk protein allergy in Bogotá, Colombia. J Pediatr Gastroenterol Nutr. 2024. 10.1002/jpn3.12203 PMid: 38587147.
16 Rodrigues VCC, Cezar TM, Abreu CLM, Sanudo A, Morais MB. A real-world cross-sectional study evaluating the role of an oral amino acid-based supplement in nutrient intake by preschoolers on a cow’s milk elimination diet. Allergol Immunopathol (Madr). 2024;52(3):42–52. 10.15586/aei.v52i3.1053. PMid: 38721954.
17 Dziechciarz P, Stróżyk A, Horvath A, Cudowska B, Jedynak-Wąsowicz U, Mól N, et al. Nutritional status and feeding difficulties in children up to 2 years of age with cow’s milk allergy. J Pediatr Gastroenterol Nutr. 2024;79(1):131–9. 10.1002/jpn3.12139. PMid: 38291802.
18 Petrus NC, Schoemaker AF, van Hoek MW, Jansen L, Jansen-van der Weide MC, van Aalderen WM, et al. Remaining symptoms in half the children treated for milk allergy. Eur J Pediatr. 2015;174(6):759–65. 10.1007/s00431-014-2456-6
19 Cortez APB, Medeiros LCS, Speridião PGL, Mattar RHGM, Fagundes Neto U, Morais MB. Pediatricians and nutritionists knowledge about treatment of cow milk allergy in infants. Rev paul pediatr. 2007;25(2):106–13. 10.1590/S0103-05822007000200002
20 Sole D, Jacob CMA, Pastorino AC, Porto Neto A, Burns DA, Sarinho ESC, et al. O conhecimento de pediatras sobre alergia alimentar: Estudo piloto. Rev Paul Pediatr. 2007; 25(4):311–6. 10.1590/S0103-05822007000400003
21 Yüce A, Dalgıç B, Çullu-Çokuğraş F, Çokuğraş H, Kansu A, Alptekin-Sarıoğlu A, et al. Cow’s milk protein allergy awareness and practice among Turkish pediatricians: A questionnaire-survey. Turk J Pediatr. 2017;59(3):233–43. 10.24953/turkjped.2017.03.002
22 Faria DPB, Cortez APB, Speridião PGL, Morais MB. Knowledge and practice of pediatricians and nutritionists regarding treatment of cow’s milk protein allergy in infants. Rev Nutr. 2018;31(6):535–46. 10.1590/1678-98652018000600003
23 van den Hoogen SCTA, van de Pol AC, Meijer Y, Toet J, van Klei C, de Wit NJ. Suspected cow’s milk allergy in everyday general practice: A retrospective cohort study on health care burden and guideline adherence. BMC Res Notes. 2014;7:507. 10.1186/1756-0500-7-507
24 Vieira SCF, Santos VS, Franco JM, Nascimento-Filho HM, Barbosa KdOeSS, Lyra-Junior DPd, et al. Brazilian pediatricians’ adherence to food allergy guidelines—A crosssectional study. PLoS One. 2020;15(2):e0229356. 10.1371/journal.pone.0229356
25 Granot M, Machnes Maayan D, Weiss B, Haberman Y, Agmon-Levin N, Shouval DS. Practice variations in the management of infants with non-IgE-mediated cow’s milk protein allergy. J Pediatr Gastroenterol Nutr. 2022;75(4):444–9. 10.1097/MPG.0000000000003556. PMid: 35797449.
26 Serdar CC, Cihan M, Yücel D, Serdar MA. Sample size, power and effect size revisited: simplified and practical approaches in pre-clinical, clinical and laboratory studies. Biochem Med (Zagreb). 2021;31(1):10502. 10.11613/BM.2021.010502. PMid: 33380887; PMCID: PMC7745163.
27 Fiocchi A, Brozek J, Schünemann H, Bahna SL, von Berg A, Beyer K, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guidelines. Pediatr Allergy Immunol. 2010;21(Suppl 21):1–125. 10.1111/j.1399-3038.2010.01068.x
28 Koletzko S, Niggemann B, Arato A, Dias JA, Heuschkel R, Husby S, 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;55:221–9. 10.1097/MPG.0b013e31825c9482
29 Taveira GR, Fernandes CDR, Silva YFR, Aquino MCB, Silva ACMV, Faria CP, et al. Evolution of nutritional status and associated factors among formula-fed infants with cow’s milk protein allergy in a government program. Arch Public Health. 2023;81(1):90. 10.1186/s13690-023-01094-3
30 Morais MB. Definição e diagnóstico. In: ILSI Brasil International Life Sciences Institute do Brasil. Alergia à proteína do leite de vaca: Uma abordagem prática: Volume 11. 1st ed. São Paulo: ILSI Brasil; 2021 (Série de publicações ILSI Brasil). Pp. 8–26.
31 Meyer R, Godwin H, Dziubak R, Panepinto JA, Foong RM, Bryon M, et al. The impact on quality of life on families of children on an elimination diet for non-immunoglobulin E mediated gastrointestinal food allergies. World Allergy Organ J. 2017;10(1):8. 10.1186/s40413-016-0139-7
32 Kansen HM, Le TM, Meijer Y, Flokstra-de Blok BMJ, Welsing PMJ, van der Ent CK, et al. The impact of oral food challenges for food allergy on quality of life: A systematic review. Pediatr Allergy Immunol. 2018;29:527–37. 10.1111/pai.12905
33 Alsaggaf A, Murphy J, Leibel S. Estimating cost-effectiveness of confirmatory oral food challenges in the diagnosis of children with food allergy. Glob Pediatr Health. 2019;6:2333794X19891298. 10.1177/2333794X19891298
34 de Faria DPB, Sillos MD, Speridião PGL, Morais MB. Outcome of food intake and nutritional status after discontinuation of a cow’s-milk-free diet post negative oral food challenge in infants and children. Allergol Immunopathol (Madr). 2022;50:1–8. 10.15586/aei.v50i1.471
35 Mehta S, Allen HI, Campbell DE, Arntsen KF, Simpson MR, Boyle RJ. Trends in use of specialized formula for managing cow’s milk allergy in young children. Clin Exp Allergy. 2022;52(7):839–47. 10.1111/cea.14180
36 Scheffer M, Biancarelli A, Cassenote A, Guilloux AGA, Miotto BA, Mainardi GM. Demografia Médica no Brasil 2018. São Paulo, SP: FMUSP, CFM, Cremesp, 2018. p.118. ISBN: 978-85-87077-55-4.
2 Toca MC, Morais MB, Vásquez-Frias R, Becker-Cuevas DJ, Boggio-Marzet CG, Delgado-Carbajal L, et al. Consensus on the diagnosis and treatment of cow milk protein allergy by the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Rev Gastroenterol Mex (Engl Ed). 2022;87(2):235–50. 10.1016/j.rgmxen.2022.01.002
3 Vandenplas Y, Broekaert I, Domellöf M, Indrio F, Lapillonne A, Pienar C, et al. An ESPGHAN position paper on the diagnosis, management, and prevention of cow’s milk allergy. J Pediatr Gastroenterol Nutr. 2024 Feb;78(2):386-413. 10.1097/MPG.0000000000003897
4 Meyer R, Venter C, Bognanni A, Szajewska H, Shamir R, Nowak-Wegrzyn A, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guideline update–VII–Milk elimination and reintroduction in the diagnostic process of cow’s milk allergy. World Allergy Organ J. 2023;16(7):100785. 10.1016/j.waojou.2023.100785
5 Sissoko NDN, Chen W, Wang C, Wu Y, Zheng X, Dong X, et al. Associations between functional constipation and non-IgE-mediated food allergy in infants and children. Allergol Immunopathol (Madr). 2023;51(3):163–73. 10.15586/aei.v51i3.738. PMid: 37169574
6 Morais MB, Toporovski MS, Tofoli MHC, Barros KV, Silva LR, Ferreira CHT. Prevalence of functional gastrointestinal disorders in Brazilian infants seen in private pediatric practices and their associated factors. J Pediatr Gastroenterol Nutr. 2022;75(1):17–23. 10.1097/MPG.0000000000003469
7 Lins MG, Horowitz MR, Silva GAP, Motta ME. Oral food challenge test to confirm the diagnosis of cow’s milk allergy. J Pediatr (Rio J). 2010;86:285–9. 10.2223/jped.2011
8 Medeiros LC, Speridião PG, Sdepanian VL, Fagundes-Neto U, Morais MB. Nutrient intake and nutritional status of children following a diet free from cow’s milk and cow’s milk by-products. J Pediatr (Rio J). 2004;80:363–70. pubmed.ncbi.nlm.nih.gov/15505731/
9 Vieira MC, Morais MB, Spolidoro JV, Toporovski MS, Cardoso AL, Araujo GT, et al. A survey on clinical presentation and nutritional status of infants with suspected cow’ milk allergy. BMC Pediatr. 2010;10:25. 10.1186/1471-2431-10-25
10 Meyer R. Nutritional disorders resulting from food allergy in children. Pediatr Allergy Immunol. 2018;29:689–704. 10.1111/pai.12960
11 Augusto EO, Bonucci VG, Cardoso RV, Morais MB. Complementary feeding and nutritional status of infants on cow’s milk proteins elimination diet. Rev Paul Pediatr. 2022;40:e20200429. 10.1590/1984-0462/2022/40/2020429IN
12 Rodrigues VCC, Speridião PGL, Sanudo A, Morais MB. Feeding difficulties in children fed a cows’ milk elimination diet. Br J Nutr. 2022;128(6):1190–9. 10.1017/S0007114521004165
13 Frizzo J, Rodrigues VCC, Speridião PGL, Morais MB. Evaluation of the complementary feeding practices, dietary intake, and nutritional status of infants on a cow’s milk protein elimination diet. J Pediatr (Rio J). 2022;98:256–63. 10.1016/j.jped.2021.06.005
14 Jardim-Botelho A, Martins TG, Motta-Franco J, Meyer R, Fontes Vieira SC, Protásio BF, et al. Growth and nutritional biomarkers in Brazilian infants with cow’s milk allergy at diagnosis and 18-month follow-up: A prospective cohort study. Pediatr Gastroenterol Hepatol Nutr. 2023;26(6):355–69. 10.5223/pghn.2023.26.6.355
15 Fakih-Botero I, Cerchiaro-Mejia MC, Rusinque MJ, Palacios-Ariza MA, Plata-Garcia CE, Peña-Hernández S. Out-of-pocket expenses and parent reported quality of life in children with cow’s milk protein allergy in Bogotá, Colombia. J Pediatr Gastroenterol Nutr. 2024. 10.1002/jpn3.12203 PMid: 38587147.
16 Rodrigues VCC, Cezar TM, Abreu CLM, Sanudo A, Morais MB. A real-world cross-sectional study evaluating the role of an oral amino acid-based supplement in nutrient intake by preschoolers on a cow’s milk elimination diet. Allergol Immunopathol (Madr). 2024;52(3):42–52. 10.15586/aei.v52i3.1053. PMid: 38721954.
17 Dziechciarz P, Stróżyk A, Horvath A, Cudowska B, Jedynak-Wąsowicz U, Mól N, et al. Nutritional status and feeding difficulties in children up to 2 years of age with cow’s milk allergy. J Pediatr Gastroenterol Nutr. 2024;79(1):131–9. 10.1002/jpn3.12139. PMid: 38291802.
18 Petrus NC, Schoemaker AF, van Hoek MW, Jansen L, Jansen-van der Weide MC, van Aalderen WM, et al. Remaining symptoms in half the children treated for milk allergy. Eur J Pediatr. 2015;174(6):759–65. 10.1007/s00431-014-2456-6
19 Cortez APB, Medeiros LCS, Speridião PGL, Mattar RHGM, Fagundes Neto U, Morais MB. Pediatricians and nutritionists knowledge about treatment of cow milk allergy in infants. Rev paul pediatr. 2007;25(2):106–13. 10.1590/S0103-05822007000200002
20 Sole D, Jacob CMA, Pastorino AC, Porto Neto A, Burns DA, Sarinho ESC, et al. O conhecimento de pediatras sobre alergia alimentar: Estudo piloto. Rev Paul Pediatr. 2007; 25(4):311–6. 10.1590/S0103-05822007000400003
21 Yüce A, Dalgıç B, Çullu-Çokuğraş F, Çokuğraş H, Kansu A, Alptekin-Sarıoğlu A, et al. Cow’s milk protein allergy awareness and practice among Turkish pediatricians: A questionnaire-survey. Turk J Pediatr. 2017;59(3):233–43. 10.24953/turkjped.2017.03.002
22 Faria DPB, Cortez APB, Speridião PGL, Morais MB. Knowledge and practice of pediatricians and nutritionists regarding treatment of cow’s milk protein allergy in infants. Rev Nutr. 2018;31(6):535–46. 10.1590/1678-98652018000600003
23 van den Hoogen SCTA, van de Pol AC, Meijer Y, Toet J, van Klei C, de Wit NJ. Suspected cow’s milk allergy in everyday general practice: A retrospective cohort study on health care burden and guideline adherence. BMC Res Notes. 2014;7:507. 10.1186/1756-0500-7-507
24 Vieira SCF, Santos VS, Franco JM, Nascimento-Filho HM, Barbosa KdOeSS, Lyra-Junior DPd, et al. Brazilian pediatricians’ adherence to food allergy guidelines—A crosssectional study. PLoS One. 2020;15(2):e0229356. 10.1371/journal.pone.0229356
25 Granot M, Machnes Maayan D, Weiss B, Haberman Y, Agmon-Levin N, Shouval DS. Practice variations in the management of infants with non-IgE-mediated cow’s milk protein allergy. J Pediatr Gastroenterol Nutr. 2022;75(4):444–9. 10.1097/MPG.0000000000003556. PMid: 35797449.
26 Serdar CC, Cihan M, Yücel D, Serdar MA. Sample size, power and effect size revisited: simplified and practical approaches in pre-clinical, clinical and laboratory studies. Biochem Med (Zagreb). 2021;31(1):10502. 10.11613/BM.2021.010502. PMid: 33380887; PMCID: PMC7745163.
27 Fiocchi A, Brozek J, Schünemann H, Bahna SL, von Berg A, Beyer K, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guidelines. Pediatr Allergy Immunol. 2010;21(Suppl 21):1–125. 10.1111/j.1399-3038.2010.01068.x
28 Koletzko S, Niggemann B, Arato A, Dias JA, Heuschkel R, Husby S, 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;55:221–9. 10.1097/MPG.0b013e31825c9482
29 Taveira GR, Fernandes CDR, Silva YFR, Aquino MCB, Silva ACMV, Faria CP, et al. Evolution of nutritional status and associated factors among formula-fed infants with cow’s milk protein allergy in a government program. Arch Public Health. 2023;81(1):90. 10.1186/s13690-023-01094-3
30 Morais MB. Definição e diagnóstico. In: ILSI Brasil International Life Sciences Institute do Brasil. Alergia à proteína do leite de vaca: Uma abordagem prática: Volume 11. 1st ed. São Paulo: ILSI Brasil; 2021 (Série de publicações ILSI Brasil). Pp. 8–26.
31 Meyer R, Godwin H, Dziubak R, Panepinto JA, Foong RM, Bryon M, et al. The impact on quality of life on families of children on an elimination diet for non-immunoglobulin E mediated gastrointestinal food allergies. World Allergy Organ J. 2017;10(1):8. 10.1186/s40413-016-0139-7
32 Kansen HM, Le TM, Meijer Y, Flokstra-de Blok BMJ, Welsing PMJ, van der Ent CK, et al. The impact of oral food challenges for food allergy on quality of life: A systematic review. Pediatr Allergy Immunol. 2018;29:527–37. 10.1111/pai.12905
33 Alsaggaf A, Murphy J, Leibel S. Estimating cost-effectiveness of confirmatory oral food challenges in the diagnosis of children with food allergy. Glob Pediatr Health. 2019;6:2333794X19891298. 10.1177/2333794X19891298
34 de Faria DPB, Sillos MD, Speridião PGL, Morais MB. Outcome of food intake and nutritional status after discontinuation of a cow’s-milk-free diet post negative oral food challenge in infants and children. Allergol Immunopathol (Madr). 2022;50:1–8. 10.15586/aei.v50i1.471
35 Mehta S, Allen HI, Campbell DE, Arntsen KF, Simpson MR, Boyle RJ. Trends in use of specialized formula for managing cow’s milk allergy in young children. Clin Exp Allergy. 2022;52(7):839–47. 10.1111/cea.14180
36 Scheffer M, Biancarelli A, Cassenote A, Guilloux AGA, Miotto BA, Mainardi GM. Demografia Médica no Brasil 2018. São Paulo, SP: FMUSP, CFM, Cremesp, 2018. p.118. ISBN: 978-85-87077-55-4.
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Jul 1, 2025
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C. Rodrigues, V. C., Fonseca, M. C. M., Solé, D., Sanudo, A., & B. Morais, M. (2025). Real-life management of gastrointestinal cow’s milk protein allergy in Brazilian infants. Allergologia Et Immunopathologia, 53(4), 68–77. https://doi.org/10.15586/aei.v53i4.1323
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How to Cite
C. Rodrigues, V. C., Fonseca, M. C. M., Solé, D., Sanudo, A., & B. Morais, M. (2025). Real-life management of gastrointestinal cow’s milk protein allergy in Brazilian infants. Allergologia Et Immunopathologia, 53(4), 68–77. https://doi.org/10.15586/aei.v53i4.1323