What is the recommended hydrolyzed formula for an infant or young child with a cow's milk protein allergy or other protein allergies?

Hydrolyzed Formula for Cow's Milk Protein Allergy

For infants with confirmed cow's milk protein allergy who cannot be breastfed, extensively hydrolyzed formula (eHF) is the first-line treatment, with 80-90% efficacy; amino acid-based formula (AAF) should be used if symptoms are severe, life-threatening, or persist after 2-4 weeks of eHF. 1

Treatment Algorithm for Formula-Fed Infants with CMPA

First-Line: Extensively Hydrolyzed Formula (eHF)

• Extensively hydrolyzed casein or whey formulas are recommended as the initial therapeutic choice for infants with confirmed cow's milk protein allergy. 1, 2, 3
• eHF demonstrates clinical efficacy in 80-90% of infants with CMPA. 1
• Both casein-based and whey-based extensively hydrolyzed formulas are safe and effective, with maximum molecular weights under 3 kDa and approximately 50% of peptides longer than four amino acids. 4
• Extensively hydrolyzed rice protein formula (eRHF) is also a safe and tolerated alternative, meeting the guideline requirement of tolerance in >90% of children with proven CMPA. 5, 3

Second-Line: Amino Acid-Based Formula (AAF)

• Switch to amino acid-based formula (such as Neocate or EleCare) if the infant has life-threatening symptoms, severe reactions, failure to thrive, or symptoms that do not resolve after 2-4 weeks of eHF treatment. 1, 6
• AAF is the most hypoallergenic option available and should be the first choice for anaphylaxis and eosinophilic esophagitis. 6, 2
• For infants with food protein-induced enterocolitis syndrome (FPIES), elemental formulas are considered the best alternative, as extensively hydrolyzed formulas may not be appropriate for all milk-triggered FPIES cases. 6

What NOT to Use

Partially hydrolyzed formulas are inadequate for treatment of confirmed cow's milk protein allergy and should never be used therapeutically. 1, 6

• Soy formula is NOT recommended as first-line treatment due to cross-reactivity affecting 20-40% of infants with CMPA. 1, 6
• Soy may only be considered for infants >6 months of age after establishing tolerance by clinical challenge, and is particularly inappropriate for FPIES. 1, 6, 2
• Goat's milk and sheep's milk are unsuitable alternatives due to high protein homology with cow's milk. 1

Management for Breastfed Infants

• Breastfeeding should be continued with complete maternal elimination of all cow's milk and dairy products, as cow's milk proteins transfer through breast milk in sufficient quantities to cause allergic reactions. 1
• Improvement typically occurs within 72-96 hours to 1-2 weeks of strict maternal dietary elimination. 1
• The mother must eliminate all sources including milk, cheese, yogurt, butter, and hidden sources in processed foods. 1
• Consultation with a registered dietitian is essential to ensure nutritional adequacy, particularly calcium supplementation. 1

Critical Monitoring and Pitfalls

Growth and Nutritional Monitoring

• All children with food allergy require nutritional counseling and regular growth monitoring (weight, length/height). 1, 6
• Children with milk allergy are more likely to consume inadequate calcium and vitamin D compared to children without milk allergy. 1
• Height-for-age percentiles may be lower in children with milk allergy, and those with 2 or more food allergies are at higher risk for growth impairment. 1

Common Pitfalls to Avoid

• Do not use partially hydrolyzed formulas for treatment of confirmed CMPA—they are inadequate and only have limited (and controversial) evidence for prevention in at-risk infants, not treatment. 7, 1, 8
• Do not delay switching to amino acid formula if the infant has failure to thrive or severe symptoms that persist despite eHF. 1
• Do not discontinue breastfeeding prematurely when maternal elimination diet can effectively manage symptoms. 1
• Do not implement empirical formula switches without recognizing the pattern of multiple food protein intolerance—move directly to an appropriate hypoallergenic option. 6
• Do not implement unnecessarily restrictive maternal diets beyond elimination of confirmed allergens, as this may compromise maternal nutrition and breastfeeding ability. 1

Special Populations

Infants with Intestinal Failure or Short Bowel Syndrome

• Breast milk is the enteral feed of first choice. 1
• If breast milk is unavailable, start with elemental (amino acid-based) formula in early infancy and severe illness, switching to extensively hydrolyzed and then polymeric feeds as tolerated. 1
• Amino acid-based formulae have shown greater efficiency in decreasing parenteral nutrition requirements compared to extensively hydrolyzed feeds. 1

Important Context: Prevention vs. Treatment

The evidence presented above is for TREATMENT of confirmed cow's milk protein allergy. For prevention, the guidance is completely different: hydrolyzed formulas (both partially and extensively hydrolyzed) are NOT recommended for prevention of allergic disease in healthy infants or even high-risk infants. 7, 8 If breastfeeding is not possible in healthy infants, standard cow's milk formula should be used. 7, 8