The use of AAFs and rice hydrolysates for the prevention of atopic disease has not been studied. Soy formulas, on the other hand, have a long history of use for atopic disease in infants. In a Cochrane review based on 5 RCTs or quasi-RCTs, the authors concluded that feeding with soy formula should not be recommended for the prevention of atopy in infants at high risk of developing allergy [38].
Treatment of Allergy
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].
Partially Hydrolyzed Formulas
pHF is tolerated by approximately 60% of milk-allergic individuals [42]. Because it contains potentially allergic CM peptides and can cause severe reactions, it is not recommended for the treatment of CMA but only for its prevention [1, 2, 17, 42].
Extensively Hydrolyzed Formulas
CM-derived eHF is the preferred treatment option in infants with CMA who are not breastfed except in the ones who refuse or do not tolerate eHF or in the most severe cases, in which AAF should be started. The majority of infants and children with CMA tolerate an eHF with whey or Cas as a nitrogen source [1]. According to the literature, a few (severe) allergic infants (2-10%) might still react to eHF-C and eHF-W [1-3, 17]. The choice of the eHF should be based on the efficacy demonstrated by scientific studies [1].
Two recent trials with a new eHF-C [43] and a new eHF-W [44] in infants with mild-to-moderate CMA showed that all confirmed CMA cases tolerated the formulas tested [1]. A symptom-based score decreased significantly in all infants within 1 month [43, 44], and the highest reduction occurred in those with challenge-confirmed CMA [43]. The thickened version of the eHF-C produced also a reduction in regurgitation in infants with positive or negative challenge [43].
HFs may indeed improve reflux-related and digestive symptoms not only by an immune mechanism but also by acting on gastric emptying time. A double-blind, randomized, crossover study compared gastric emptying in 20 healthy newborns fed CM-SF, pHF and eHF containing 50 ml 13C-octanoic acid. eHF resulted in significantly faster gastric emptying than SF and pHF (medians 46 vs. 55 and 53 min, respectively) [45].
There is limited evidence that the addition of pre- or probiotics (e.g. Lactobacillus rhamnosus GG, LGG, or Bifidobacterium lactis) to eHF offer an additional benefit [46, 47].
A cohort study in 412 infants with CMA with data extracted from the Truven Health MarketScan® Commercial Claims Database in the US showed that 56% of infants fed eHF-C enriched with the probiotic LGG were estimated to have been successfully managed by 9 months compared to 38% of eHF-C-fed infants and 35% of AAF-fed infants (p < 0.05 and p = 0.003, respectively) [48]. Infants in the AAF group used significantly more health care resources and prescribed drugs than infants in the other two groups. The estimated costs of managing a CMA infant over the first 12 months following the start of feeding were USD 3,577, 3,781 and 6,255 for an infant fed eHF-C plus LGG, eHF-C only and AAF, respectively [48].
Rice-Based Extensively Hydrolyzed Formulas
One prospective open, randomized
