Table 1.

Summary of the recommendations

Question 1: Which milk replacement formula should be used in infants with IgE-mediated CMA who are not being breastfed, and in what order? This broader question entailed the comparison of 4 different interventions: -extensively hydrolyzed formula (eHF-CM) -amino acid formula (AAF) -hydrolyzed rice formula (HRF) -soy formula.

Recommendation 1: When choosing a formula in infants with IgE-mediated CMA who are not being breastfed, we suggest an extensively hydrolyzed (cow's milk) formula or a hydrolyzed rice formula as the first option, an amino-acid formula as the second option, and a soy formula as the third option. (Conditional recommendation based on very low certainty evidence about health effects) Remarks 1.Children should not receive the formula to which they previously reacted. 2.A small proportion of children may react to extensively hydrolyzed formula or soy formula when receiving it for the first time (there is no information whether the same applies to hydrolyzed rice formula but there is also no information that it does not)

Question 2: Which milk replacement formula should be used in infants with non-IgE-mediated CMA who are not being breastfed, and in what order? This broader question entailed the comparison of 4 different interventions: -extensively hydrolyzed formula (eHF-CM) -amino acid formula (AAF) -hydrolyzed rice formula (HRF) -soy formula.

Recommendation 2: When choosing a formula in infants with non-IgE-mediated CMA who are not being breastfed, we suggest an extensively hydrolyzed (cow's milk) formula or hydrolyzed rice formula as the first option, amino-acid formula as the second option, and soy formula as the third option.(Conditional recommendation based on very low certainty evidence about health effects) Remarks 1)In settings where soy formula is a viable option, sensitization to soy should be considered in the decision-making process for managing patients known not to respond to an avoidance diet with eHF-CM (ie, children with FPIES or FPIAP).

Question 3: Should a formula with probiotics vs the same formula without probiotics be used for infants with IgE-mediated CMA?

Recommendation 3: When choosing a formula with or without a probiotic for infants with IgE-mediated CMA, we suggest either a formula without a probiotic or eHF-CM containing Lacticaseibacillus rhamnosus (LGG). (Conditional recommendation based on very low certainty evidence about health effects)Remarks 1)While DRACMA does not endorse any specific commercial product, current research evidence is only available for extensively hydrolyzed casein formula with Lacticaseibacillus rhamnosus (formerly Lactobacillus rhamnosus). Other formulas for managing IgE-mediated CMA combined with other probiotics have not been studied. 2)For advice about using formulas without a probiotic see Recommendation 1 3)This recommendation does not apply to children without confirmed CMA.

Question 4: Should a formula with probiotics vs the same formula without probiotics be used for infants with non-IgE-mediated CMA?

Recommendation 4: When choosing a formula with or without a probiotic for infants with non-IgE-mediated CMA, we suggest either a formula without a probiotic or eHF-CM containing Lacticaseibacillus rhamnosus (LGG). (Conditional recommendation based on very low certainty evidence about health effects) Remarks 1)While DRACMA does not endorse any specific commercial product, at this moment research evidence is only available for extensively hydrolyzed casein formula supplemented with Lacticaseibacillus rhamnosus (LGG) or with L. casei CRL431/B. lactis Bb12 (currently there is no commercially available formula supplemented with L. casei CRL431/B. lactis Bb12). Other formulas used for managing non IgE-mediated CMA combined with other probiotics have not been studied. 2)For advice about using formulas without a probiotic see Recommendation 2. 3)This recommendation does not apply to children without confirmed CMA.