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The basic treatment of CMA is avoidance of intact CMPs. In early childhood, a milk substitute is needed and, if the diagnosis of CMA is confirmed, the elimination diet in the nonbreastfed infant using an eHF with documented efficacy are recommended by all allergy guidelines, and the therapeutic formula should be maintained for 6 months or until 9-12 months of age [1].

pHF should not be used because of a high degree of antigenicity and allergenicity. Although lower than pHF, residual allergenicity is present even in eHF whilst the only anallergic formulas are the elemental ones based on AAFs that cannot determine an immune stimulation [1-3]. AAFs are peptide-free formulas that contain mixtures of essential and nonessential amino acids [17]. AAFs are only indicated in treatment. AAFs are recommended for infants who refuse or do not tolerate eHF or in the most severe cases of CMA [1-3]. Compared to eHFs, costs of AAFs are higher in most countries, and they have a different taste and, possibly, a different long-term nutritional effect [2, 39].

Soy protein is as allergenic as CMP [2], although there are also reviews that conclude that soy allergy is less frequent [40]. According to ESPGHAN, soy formulas are not recommended for infants <6 months of age [1], although the American Academy of Pediatrics does not make this difference according to age [17]. Alternative milk substitutes such as sheep’s and goat’s milk should not be used because of a high degree of cross-reactivity with CMP [2]. Milk from other mammals such as mares and donkeys may be tolerated by some children with CMP allergy [2]; however, to the best of our knowledge, there is no infant formula on the market derived from mares or donkeys, and thus these milk formulas cannot be recommended for infants and young children because of nutritional inadequacy.

Recent treatment modalities such as oral immunotherapy involving the ingestion of increasing amounts of milk allergen on a regular basis to desensitize and potentially make patients permanently tolerant have been developed [41]. Currently, this strategy cannot be applied in young children [41].