Latest review outlines opportunities for cow’s milk protein allergy management

Summary of review by Zepeda-Ortega et al 2021

15 experts in the field of immunology and allergy recently published a review on the management of cow’s milk protein allergy (CMPA), and covered opportunities for future research.

Primary prevention of CMPALatest review outlines opportunities for cow’s milk protein allergy prevention and management

The authors wrote that primary prevention of CMPA should start even before pregnancy, with a focus on healthy lifestyle and food diversity. This is especially relevant for mothers with history of allergic diseases and planned Caesarean section delivery. During pregnancy the transfer of IgG-allergen complexes provides early food allergen exposure for the fetus. Postnatally, the authors recommended continued exposure to cow’s milk among milk-drinking breastfeeding mothers, as transfer of IgG-allergen complexes via breastmilk may help to build tolerance to milk proteins.

The review also noted that in non-breastfed, high risk infants with family history of allergy, partially hydrolysed formulas (pHF) with proven efficacy, may play a preventive role and provide some economic benefits. However, the authors cautioned that additional research is required before forming conclusive statements.

Focus on early oral tolerance

As written in the review, the new paradigm on clinical management of CMPA should focus on the development of early oral tolerance and not only on symptoms resolution. Generally, extensively hydrolysed formulas (eHF) are recommended as first line management for non-breastfed infants with mild-to-moderate CMPA. The review stated that pre- and probiotics, and long-chain polyunsaturated fatty acids (LCPUFA), especially during pregnancy, may also be considered to support development of early oral tolerance. According to the authors, eHF has an advantage over amino acid formulas (AAF) when it comes to developing oral tolerance because it is more cost effective and has the ability to induce tolerance as it contains small milk protein-derived peptides, which AAF do not.

Another way to develop tolerance is via stepwise introduction of formulas with various degrees of hydrolysis in a milk formula ladder in addition to the available baked-milk ladders, the authors wrote (Figure 1). However, this requires further controlled trials before it can be recommended for routine practice.

The review suggested several opportunities for further research

First, pre- and probiotics supplementation for mothers and high risk infants as a strategy for primary prevention of CMPA. Second, a step-down milk formula ladder with various degrees of hydrolysate for food challenges and early development of oral tolerance (Figure 1). This provides a more precise gradation of milk protein-derived peptide introduction in the diet than is currently used in clinical practice. Third, as evidence suggests environmental modification may have a greater beneficial impact on allergy risks than previously thought, a multi-faceted approach should be explored in prevention trials conducted during preconception and pregnancy (Figure 2). The approach should involve an optimized diverse diet with no food allergen avoidance, no smoking, and if possible, avoidance of antibiotics and caesarean section delivery.

Figure 1. A step-down and step-up milk ladder may support development of early tolerance

Figure 2. Factors that may influence breast milk composition and potentially, immunological outcomes in the child

Read more:


Zepeda-Ortega B, et al. Strategies and future opportunities for the prevention, diagnosis and management of cow milk allergy.

Important note

Breastfeeding is the best nutrition for healthy growth and development of babies. Exclusive breastfeeding for six months is the optimal way of feeding infants. Thereafter infants should receive complementary foods with continued breastfeeding up to two years or beyond. Mothers should receive guidance on proper maternal nutrition in order to help sustain an adequate supply and quality of breast milk. Unnecessary introduction of bottle-feeding, partially or fully, or of other complementary foods and drinks may have a negative impact on breastfeeding, which may be irreversible. Mothers should consult their doctor and consider the social and financial implications before deciding to use breast milk substitutes or if they have difficulty breastfeeding. Usage, preparation and storage instructions of breast milk substitutes or of other complementary foods and drinks should be followed carefully as improper or unnecessary use may pose a health hazard.