Cow's Milk Allergy | Perrigo Pediatrics

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Meets AAP Criteria for Hypoallergenicity

Extensively hydrolyzed proteins derived from cow’s milk, in which the protein is in the form of free amino acids and peptides <1.5 kDa, have been used in formulas for over 50 years for infants with severe inflammatory bowel diseases or cow’s milk allergy.¹²

The proteins in extensively hydrolyzed infant formula are predominantly subjected to enzymatic hydrolysis in order to reduce the peptide size, and, consequently, the allergenicity of the proteins.¹³ Smaller-sized proteins reduce the risk of triggering an allergic reaction.

Hydrolysis Characteristics Molecular Weight Profile (area %)

Store Brand Hypoallergenic Infant Formula contains low molecular weight peptides to provide reduced allergenicity. Hypoallergenic infant formula derived from cow’s milk should have most of the nitrogen in the form of free amino acids and peptides at <1500 Da.¹⁷ The molecular weight profile obtained by size exclusion chromatography for Store Brand Hypoallergenic confirms that the majority of the protein (85%) have been hydrolyzed to a molecular size of less than 500 Da.

Compare the Protein Degree of Hydrolysis

The protein sizes can be compared with analytical methods, using for example a SDS-PAGE gel experiment, which separates the different protein sizes in a gel-like matrix. The gel functions like a sieve through which the proteins move in response to an electric field. Denaturated proteins can be seperated by size as they migrate towards the positive electrode (on the bottom of the gel in the picture). Large unhydrolyzed proteins appear as dark, distinct bands within a lane and lower bands represent smaller protein sizes. The absence of these bands in columns 5 and 6 indicate very low or non-existent protein of higher molecular weight.

See the Difference in Protein

Laboratory findings show clear differences in overall protein composition when compared to routine formulas
Store Brand Hypoallergenic Infant Formula is comprised of extensively hydrolyzed proteins

Compare the Amino Acid Profiles

The protein quality and quantity are important aspects of the nutritional value when feeding infants.¹⁷ In hypoallergenic infant formula, the proteins are hydrolyzed and the presence of the appropriate essential and non-essential amino acids determines the nutritional value that supports infant growth and development.

All of the hypoallergenic infant formulas below provide a well balanced amino acid profile that supports infant growth and development.

Amino Acid Chart

Compare Store Brand Hypoallergenic Infant Formula to Leading Name Brands

Hypoallergenic Infant Formula Comparison Chart

About CMA

CMA can affect up to 3% of babies during the first year of life and is one of the most common food allergies during infancy.⁵ CMA is believed to result from the failure to develop normal tolerance, which can result in IgE mediated symptoms, non-IgE mediated symptoms, or occasionally, both.⁶ However, in clinical practice it is often not possible to distinguish between IgE- and non-IgE mediated CMA based on history and physical examination alone.⁷ IgE and non-IgE allergy mediated reactions can affect four major systems of the body with a variety of symptoms.⁶

IgE-mediated symptoms develop immediately – within minutes to an hour

Non-IgE-mediated symptoms present delayed onset symptoms occurring from one hour to several days after ingestion of milk.

How CMA is recognized by the infant immune system

CMP Being Tolerated by Non-Allergic Infant Immune Response

In an infant, food components are assessed for their tolerability. When routine infant formula is consumed, immune cells like the macrophages in the gastrointestinal tract can sample antigens in the gut lumen. Antigen presenting cells (APC) like dendritic cells (DC) communicate the information to T cells, recognizing specific epitopes from proteins. In a tolerogenic situation the cytokine profile stimulates naïve T cells to differentiate into regulatory T cells (Treg). Treg play a crucial role in modulating the immune response and in developing tolerance.⁸ In a non-allergic infant, the immune system is recognizing the antigen as harmless, tolerating the milk proteins.

CMP is Not Tolerated by an Allergic Infant Immune Response

an allergic infant, the immune system is recognizing milk proteins as harmful antigens because Immune cells initiate an inflammatory response. APCs present the antigen to T cells, which recognize specific epitopes that trigger the differentiation into Th2 cells, cytokines like IL-4, IL-5 or IL-13 are released. These cytokines influence B cells.⁹ Activated B cells can also circulate to the respiratory system or skin, causing inflammatory reactions which can result in clinical manifestations of CMA.⁶ In the gastrointestinal system the inflammatory mediators like Th2 cytokines can impair the intestinal epithelial gut barrier and an influx of antigens can occur, causing mast cells to release histamine, resulting in allergic reactions.¹⁰

Immune System Tolerates Extensively Hydrolyzed Proteins in Allergic or Non-Allergic Infant

Hypoallergenic infant formula contains proteins which are extensively hydrolyzed into small peptides and amino acids. When the epitopes from cow’s milk proteins are not present and therefore not recognized by T cells as ’foreign’, immune cells don’t elicit an inflammatory response, which can improve the gut barrier, decreasing antigen uptake. This reduced allergenicity can lead to reduced T cell reactivity. Without inflammatory cytokines, Th2 cell differentiation and B cell stimulation, IgE is not released and consequently mast cells don’t release histamine that could result in allergic symptoms.⁸

CMP Being Tolerated by Non-Allergic Infant Immune Response

CMP is Not Tolerated by an Allergic Infant Immune Response

Immune System Tolerates Extensively Hydrolyzed Proteins in Allergic or Non-Allergic Infant

The High Cost of Allergies

Parents of infants with CMA are challenged to provide complete nutrition at a time of life when breast milk or infant formula is a mainstay of the diet. CMA can be a source of parental and family stress due to a milk-free diet and can lead to a subsequent nutritional deficiency if not treated appropriately.⁴ Early life may be a key window of opportunity in modulating or “educating” the infant immune system.

The Allergic March10

Many children will outgrow CMA by 3-4 years of age. However, studies have shown that infants with food allergies such as CMA are 2 to 4 times more likely to develop other atopic conditions by age 5.

Help families understand the risks and cost implications of food allergies

The food allergy with the highest average costs and services per patient in 2016 was milk product allergy, which generally tends to be associated with the youngest patients (infants and toddlers) and with prescription formulas.¹⁹

1.2%

increase of childhood food allergy prevalence every decade²⁰

food allergy prevalence in non-Hispanic black children vs. white children²⁰

1/5

of all childhood food allergies due to milk allergy²⁰

377%

rise in diagnoses of anaphylactic food reactions from 2007 to 2016¹⁹

$4,184

Estimated economic cost per child with food allergy per year²¹

¹Pediatric Nutrition (8th Edition) ; ISBN electronic: 978-1-61002-361-0 ; ISBN print: 978-1-61002-360-3 ; Publication date: January 2020.
²Barber, C, Prieto, P.A., Wallingford, J.C. (2018). A Double-Blind, Randomized, Crossover Allergy Study of an Extensively Hydrolyzed Casein Formula. Journal of Nutrition and Food Sciences.
³Calculations based on March 2021 IRi Market Advantage annual retail sales data of Similac® Alimentum®, Enfamil® Nutramigen® and Perrigo’s MSRP of hypoallergenic infant formula cost per pound based on an average weekly usage of 1.5 pounds of powder the first year. Pricing, reconstitution rates and infant formula consumption may vary. MSRP is manufacturer-suggested pricing only, retailers alone set pricing, cost savings may vary.
⁴Edwards CW, Younus MA. Cow Milk Allergy. [Updated 2019 Nov 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan.
⁵Flom, D., Julie , Sicherer, H., Scott. (2019). Epidemiology of Cow’s Milk Allergy. Nutrients, 5, 1051. https://doi.org/10.3390/nu11051051
⁶Fiocchi, A., Brozek, J., Schünemann, H., Bahna, S. L., von Berg, A., Beyer, K., Bozzola, M., Bradsher, J., Compalati, E., Ebisawa, M., Guzman, M. A., Li, H., Heine, R. G., Keith, P., Lack, G., Landi, M., Martelli, A., Rancé, F., Sampson, H., Stein, A., … Vieths, S. (2010). World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines. The World Allergy Organization journal, 3(4), 57–161. https://doi.org/10.1097/WOX.0b013e3181defeb9
⁷Koletzko, S., Niggemann, B., Arato, A., Dias, J., Heuschkel, R., Husby, S., … Vandenplas, Y. (2012). Diagnostic Approach and Management of Cow's-Milk Protein Allergy in Infants and Children. Journal of Pediatric Gastroenterology and Nutrition, 55(2), 221–229. doi: 10.1097/mpg.0b013e31825c9482
⁸D’Auria, E., Salvatore, S., Pozzi, E., Mantegazza, C., Sartorio, M. U. A., Pensabene, L., … Zuccotti, G. (2019). Cow’s Milk Allergy: Immunomodulation by Dietary Intervention. Nutrients, 11(6), 1399. doi: 10.3390/nu11061399
⁹Giovanna, V., Carla, C., Alfina, C., Domenico, P., & Elena, L. (2012). The immunopathogenesis of cow’s milk protein allergy (CMPA). Italian Journal of Pediatrics, 38(1), 35. doi: 10.1186/1824-7288-38-35
¹⁰Bruewer, M., & Nusrat, A. (2000). Regulation of Paracellular Transport across Tight Junctions by the Actin Cytoskeleton. Tight Junctions, 135–145. doi: 10.1007/0-387-36673-3_10
¹¹Bishop, J. M., Hill, D. J., & Hosking, C. S. (1990). Natural history of cow milk allergy: clinical outcome. The Journal of Pediatrics, (6), 862.
¹²American Academy of Pediatrics (2000) Committee on Nutrition. Hypoallergenic infant formulas, Pediatrics 106: 346-349.
¹³Hays T, Wood RA. A Systematic Review of the Role of Hydrolyzed Infant Formulas in Allergy Prevention. Arch Pediatr Adolesc Med. 2005;159(9):810–816. doi:10.1001/archpedi.159.9.810
¹⁴Kleinman RE, Bahna S, Powell GF, Sampson HA. Use of infant formulas in infants with cow milk allergy: a review and recommendations. Pediatr Allergy Immunol. 1991; 2:146–155
¹⁵World Health Organization recommended amount of DHA is 0.2% - 0.36% of total fatty acids.
¹⁶Calculations based April 2022 IRI Market Advantage latest 26 weeks sales data comparing store brand extensively hydrolyzed hypoallergenic powder infant formula to average national brand extensively hydrolyzed powder infant formula cost per pound. MSRP is manufacturer-suggested pricing only, retailers alone set pricing, cost savings may vary.
¹⁷Zhang et al. 2013, Amino acid profiles in term and preterm human milk through lactation: a systematic review
¹⁸Data on file. Compiled based on August 2020 third-party testing and public information online.
¹⁹Fair Health. Food Allergy in the United States: Recent Trends and Costs. An Analysis of Private Claims Data. https://s3.amazonaws.com/media2.fairhealth.org/whitepaper/asset/Food%20Allergy%20White%20Paper%20Final.compressed.pdf.
²⁰Savage, J., & Johns, C. B. (2015). Food allergy: epidemiology and natural history. Immunology and allergy clinics of North America, 35(1), 45–59. https://doi.org/10.1016/j.iac.2014.09.004
²¹Gupta R, Holdford D, Bilaver L, et al. The Economic Impact of Childhood Food Allergy in the United States. JAMA Pediatr. 2013;167(11):1026-1031.

Fiocchi, A., Brozek, J., Schünemann, H., Bahna, S. L., von Berg, A., Beyer, K., Bozzola, M., Bradsher, J., Compalati, E., Ebisawa, M., Guzman, M. A., Li, H., Heine, R. G., Keith, P., Lack, G., Landi, M., Martelli, A., Rancé, F., Sampson, H., Stein, A., … Vieths, S. (2010). World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines. The World Allergy Organization journal, 3(4), 57–161. https://doi.org/10.1097/WOX.0b013e3181defeb9

Hypoallergenic

Meets AAP Criteria for Hypoallergenicity

Moms Pay the Price for Colic Due to Cow’s Milk Allergies

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Hydrolysis Characteristics Molecular Weight Profile (area %)

See the Difference in Protein

How CMA is recognized by the infant immune system

CMP Being Tolerated by Non-Allergic Infant Immune Response

CMP is Not Tolerated by an Allergic Infant Immune Response

Immune System Tolerates Extensively Hydrolyzed Proteins in Allergic or Non-Allergic Infant

CMP Being Tolerated by Non-Allergic Infant Immune Response

CMP is Not Tolerated by an Allergic Infant Immune Response

Immune System Tolerates Extensively Hydrolyzed Proteins in Allergic or Non-Allergic Infant

The Allergic March10

Help families understand the risks and cost implications of food allergies

Help Families Get Up to 8 Days1 of Store Brand Infant Formula for Free, After Rebate!