Inside the Tin

Inside The Tin: A Guide To Infant Formula For The Management Of Cows’ Milk Protein Allergy

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Inside the tin
Nutritional support in early life is an essential part of the clinical management of infants with food allergies, such as cows’ milk protein allergy (CMPA). Several different types of infant formulas — such as extensively hydrolysed, plant-based (soy, rice) and amino acid-based formulas — are available to manage CMPA. How do you select the most appropriate one? Do we need to think beyond just controlling symptoms?
Types of formula for management of CMPA

The Australasian Society of Clinical Immunology and Allergy (ASCIA) emphasises that while breast milk is the first choice for all infants including those with food allergy, a specialised formula is recommended for infants with confirmed CMPA when breastfeeding is not possible.1 There are several different types of specialised formula appropriate for managing infants with CMPA: extensively hydrolysed, plant-based (soy, rice) and amino acid-based formulas.1,2

Extensively hydrolysed formulas

Extensively hydrolysed formulas (eHF) have been treated with enzymes to break down most of the cows’ milk proteins into smaller, hypoallergenic protein fragments. eHFs are recommended by ASCIA as the first-choice treatment in mild to moderate cows’ milk allergic infants (<6 months) and is tolerated by 90% of infants with cows’ milk protein allergy.3,4 Some infants may still react to the protein chains in eHFs; therefore, it is not recommended in babies who have had anaphylaxis to cows’ milk.3,4

Amino acid-based formulas

Amino acid-based formulas (AAF) are used in severe cases, such as anaphylaxis, enteropathy, eosinophilic esophagitis and food protein induced enterocolitis syndrome (FPIES), as well as cases of multiple food protein allergies, severe atopic dermatitis and intolerance to eHF or soy protein-based formula (prevalent in ~1 in 10 infants with CMPA).4,5 Instead of being based on whole or broken-down cows’ milk protein, these formulas are based on amino acids and are small enough to not be recognised as ‘harmful’ by the immune system.3,4

differences in allergenicity
Soy protein-based formulas

Soy infant formulas contain soy protein derived from soy flour, and a mixture of carbohydrates in the form of sucrose and corn syrup.6 Soy is not recommended in the treatment of CMPA before 6 months of age due to a risk of cross-reactivity: up to 14% of infants with IgE-mediated CMPA and up to 60% of infants with non-IgE-mediated CMPA will also have a reaction to soy.7

Rice protein-based formula

Rice protein-based formulas are considered a second-line option in the treatment of CMPA as an alternative formula to eHF or soy protein formula. Rice formulas should be continued or changed based on specialist advice and are contraindicated in babies with FPIES to rice.4

Not a ‘one size fits all’ approach

Australian guidelines recommend that the type of specialised formula selected be tailored to the infants age, severity and type of allergy.1,2,8

For an overview of the treatment guidelines for diagnosed CMPA, read our article on Demystifying cows’ milk protein allergy

Read article

According to ASCIA, infants allergic to both cows’ milk and soy should continue to take specialised formula until 2 years of age.1 It is also important to note that more than 90% of infants with CMPA will react to other mammalian milks due to similarities in protein structure to cows’ milk protein.3 Milk options that are NOT recommended for infants with CMPA are listed in the table below:3

infant formula not recommended in cmpa

Emerging evidence indicates that in high-risk infants who are unable to be breast-fed, choosing a cows’ milk-based eHF can promote immunologic tolerance and help prevent atopic manifestations later in life. While formulas that are based on other protein sources (such as soy and rice) appear to have no protective effect.5,9–13

Looking beyond symptom relief

In recent years, there has been a paradigm shift in how CMPA is managed. Previously, the goal was to control symptoms with a focus on allergen avoidance. Treatment is now moving towards a more proactive (tolerance induction) strategy in response to the emerging research indicating that early exposure of allergenic foods in small amounts may help to prevent atopy in at-risk children and promote oral tolerance.5,6In infants at high risk and who are unable to be completely breast fed, prolonged feeding with a hypoallergenic cows’ milk protein-based formula (such as eHFs) may help reduce infant and childhood allergy.6 Prolonged used of soy formulas, however, may worsen atopic illness (use of rice protein in the prevention of atopic disease has not been studied).10The combination of eHFs and pre- and probiotics is also being explored, with evidence to indicate an accelerated development of oral tolerance in children with IgE-mediated CMPA and a reduced incidence of other allergic manifestations compared to eHF alone.5,9

Role of synbiotics in immune system development

There is now a greater appreciation of how crosstalk between the gut microbiome and immune system influences allergy development during infancy and diseases later in life.5,9 Gut microbiota dysbiosis, an imbalance of gut bacteria is often associated with the development of CMPA.14–16 It is thought that gut microbiota dysbiosis impacts immune system development, leading to CMPA. As a result, the focus has now shifted from allergen avoidance to supporting healthy immune response via modulation of the gut microbiota.5 Synbiotics are a combination of a pre- and probiotics that work synergistically to rebalance the gut microbiota. With a growing body of clinical evidence to suggest that synbiotics can have a beneficial effect in infants with CMPA, selected Nutricia products contain the synbiotic, SYNEO, to help rebalance microbiota and support immune system development. 17–19

Aptamil AllerPro SYNEO
Key ingredients to consider

Many formulas are fortified with additional ingredients, what are the key ones for consideration in CMPA?

ingredients for cmpa
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  1. ASCIA. Guide for Milk Substitutes in Cow’s Milk Allergy. Available at: ASCIA_HP_Guide_CMA_Milk_Substitutes_2020.pdf
  2. Kemp et al. Med J Aust. 2008;188(2):109–112.
  3. ASCIA HP Information Paper. Nutritional Management of Food Allergy. September 2013.
  4. ASCIA. Cow’s Milk (Dairy) Allergy. Available at: ASCIA_PCC_Cows_milk_dairy_allergy_2019.pdf (accessed April 2021).
  5. Sackesen C et al. Front Pediatr 2019;7:372.
  6. RACP. Paediatric Policy: Soy Protein Formula. November 2006.
  7. Walsh J et al. Br J Gen Pract 2016;66:e609–11.
  8. Preece K et al. N Z Med J 2016;129:78-88.
  9. D’Auria E et al. Nutrients 2019;11:1399.
  10. NHMRC. Eat for health. Infant Feeding Guidelines. Information for health workers. December 2012.
  11. Carucci l et al. Front Pediatr 2020;8:440.
  12. Sánchez‐Valverde F et al. Allergy 2009;64(6):884–9.
  13. Prescott SL, Tang M. Position Statement: Allergy prevention in children. ASCIA, October 2004.
  14. Berni Canani R et al. ISME J 2016;3:42–50.
  15. Ling Z et al. Appl Environ Microbiol 2014;80:2546–54.
  16. Thompson-Chagoyan OC et al. Pediatr Allergy Immunol 2010;21:e394–400.
  17. Candy DCA et al. Pediatr Res 2018;83:677–86.
  18. Fox AT et al. Clin Transl Allergy 2019;9:5.
  19. Van der Aa LB et al. Clin Exp Allergy 2010;40:795–804.
  20. Łoś-Rycharska E et al. Gastroenterology Rev 2016;11:226–31.
  21. Burks W et al. J Pediatr 2008;2:P266–71.
  22. van den Elsen LWJ et al. Clin Exp Allergy 2013;43:798–810.
  23. Hoppenbrouwers T et al. Front Immunol 2019;10:1118.

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A nutritionally complete, premium extensively hydrolysed formula (eHF) for infants from birth (0-6 months) with confirmed mild to moderate cows’ milk and/or soy protein allergy (not anaphylaxis), requiring a partial or complete breast milk substitute.
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