What are the ESPGHAN (European Society for Pediatric Gastroenterology, Hepatology, and Nutrition) guidelines for managing Cow's Milk Protein Allergy (CMPA)?

ESPGHAN Guidelines on Cow's Milk Protein Allergy

Diagnostic Approach

The diagnosis of CMPA requires elimination of cow's milk proteins from the infant's diet followed by clinical response assessment, with oral food challenge as the gold standard for confirmation. 1, 2

• Skin prick tests, patch tests, and serum-specific IgE are only indicative of CMPA and cannot definitively diagnose the condition, particularly for non-IgE mediated gastrointestinal manifestations. 2, 3
• A double-blind placebo-controlled food challenge (DBPCFC) remains the gold standard for diagnosis, though clinical response to elimination followed by rechallenge is acceptable in practice. 1, 2
• In patients with predominantly gastrointestinal manifestations, sigmoidoscopy and rectal biopsy may be considered as an alternative diagnostic approach. 3

Management for Breastfed Infants

Breastfeeding should be continued with maternal elimination of cow's milk and dairy products from the diet, as cow's milk proteins transfer through breast milk in sufficient quantities to cause allergic reactions. 4, 5, 6

• The mother must completely eliminate all sources of cow's milk protein including milk, cheese, yogurt, butter, and hidden sources in processed foods. 5
• Improvement typically occurs within 72-96 hours to 1-2 weeks of strict maternal dietary elimination. 4, 5
• Consultation with a registered dietitian is essential to ensure nutritional adequacy of the maternal diet, with particular attention to calcium supplementation. 5, 6
• If symptoms persist despite strict maternal elimination for 2 weeks, consultation with an allergy specialist is warranted. 5
• A rechallenge after 1-2 weeks of elimination should be performed to confirm the diagnosis before implementing longer periods of dietary restriction. 6

Management for Formula-Fed Infants

For formula-fed infants, an extensively hydrolyzed formula (eHF) of cow's milk protein is the first-line treatment, with demonstrated efficacy of 80-90%. 4, 5, 1

• Extensively hydrolyzed casein-based formula is the preferred first choice for most infants with CMPA. 6, 1, 7
• An amino acid-based formula (AAF) should be used if symptoms are life-threatening, severe, or do not resolve after 2-4 weeks of eHF treatment. 4, 5, 7
• Rice protein-based extensively hydrolyzed formula can serve as an alternative to cow's milk protein-based eHF. 1
• Soy formula is NOT recommended as a first-line alternative due to cross-reactivity affecting 20-40% of infants with CMPA; it may only be considered for infants >6 months after establishing tolerance by clinical challenge. 4, 5, 1
• Goat's milk and sheep's milk are unsuitable alternatives due to high protein homology with cow's milk. 5, 6

Duration and Monitoring

The elimination diet should be strictly followed for at least 9-12 months before attempting reintroduction. 1

• Most infants return to their usual state of health within 3-10 days of switching to hypoallergenic formula or maternal elimination diet, with a median resolution time of 5 days. 4
• CMPA usually resolves during the first 2-3 years of life, though IgE-mediated forms tend to be more persistent. 1
• An oral food challenge should be carried out in a hospital setting at 9-12 months of age to assess tolerance development. 1
• Reintroduction of cow's milk protein should be attempted under medical supervision, typically after 6-12 months of elimination, with timing individualized based on severity of initial symptoms. 4, 5, 6

Special Considerations for Intestinal Failure

In newborns and infants with intestinal failure or short bowel syndrome, breast milk is the enteral feed of first choice. 8

• 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. 8
• There is evidence that breast milk is associated with shorter duration of parenteral nutrition in intestinal failure. 8
• Amino acid-based formulae have shown greater efficiency in decreasing parenteral nutrition requirements compared to extensively hydrolyzed feeds in case series. 8

Critical Pitfalls to Avoid

• Do not implement unnecessarily restrictive maternal diets beyond elimination of confirmed allergens, as this may compromise maternal nutrition and breastfeeding ability. 4, 5, 6
• Do not discontinue breastfeeding prematurely when maternal elimination diet can effectively manage symptoms. 5
• Do not use regular soy formula as first-line treatment due to significant cross-reactivity risk. 4, 5
• Do not delay switching to amino acid formula if the infant has failure to thrive or severe symptoms that persist despite eHF. 4, 5
• Avoid diagnosing CMPA without proper elimination and rechallenge, as unjustified elimination can be harmful. 1