What is the management approach for cow milk protein allergy (CMPA) in neonates?

Presentation and Management of Cow Milk Protein Allergy in Neonates

Clinical Presentation

Cow milk protein allergy (CMPA) in neonates presents most commonly with gastrointestinal, dermatological, and respiratory manifestations, with an incidence of 2-7.5% in the first year of life, and can occur even in exclusively breastfed infants at a rate of 0.5%. 1, 2

System-Specific Manifestations

• Gastrointestinal symptoms are the most common presentation and include bloody stools (allergic proctocolitis), vomiting, diarrhea, colic, and failure to thrive 1, 3
• Dermatological manifestations include atopic dermatitis and eczema, particularly in infants with early-onset severe eczema who are at highest risk 4, 1
• Respiratory symptoms can occur but are less common in neonates 1
• Symptoms in breastfed infants develop due to transfer of cow milk proteins through maternal breast milk, though the exact mechanisms remain under investigation 2

Diagnostic Approach

Diagnosis requires clinical suspicion based on symptoms, followed by elimination of cow milk protein from the diet, with resolution typically occurring within 72-96 hours in allergic proctocolitis or 1-4 weeks for other manifestations. 5, 6

• For non-IgE mediated CMPA (most common in neonates with gastrointestinal symptoms): skin prick testing and specific IgE levels are not useful 3
• Clinical response to elimination diet followed by positive oral food challenge is diagnostic 3
• In patients with only gastrointestinal manifestations, sigmoidoscopy and rectal biopsy may be considered as an alternative diagnostic approach 3
• Laboratory testing plays only a supporting role; diagnosis is primarily clinical 7

Management Algorithm

For Breastfed Infants

Breastfeeding should continue with strict maternal elimination of all cow milk and dairy products from the mother's diet, as this aligns with infant feeding recommendations and effectively manages symptoms in most cases. 5, 6

• The mother must eliminate all sources of cow milk protein including milk, cheese, yogurt, butter, and hidden sources in processed foods 6
• Consultation with a registered dietitian is recommended to ensure nutritional adequacy, with particular attention to calcium supplementation 6
• Improvement typically occurs within 1-2 weeks of strict maternal elimination 6
• If symptoms persist despite strict maternal dietary elimination for 2 weeks, consultation with an allergy specialist is warranted 6
• Avoid unnecessarily restrictive maternal diets beyond cow milk elimination unless other food allergies are confirmed 6

For Formula-Fed Infants

The first-line treatment is extensively hydrolyzed formula (eHF) of cow milk protein, which has 80-90% success rate. 5, 8

• For infants with severe reactions or life-threatening symptoms, amino acid-based formula (AAF) should be used as first-line treatment 6
• If eHF is not tolerated, switch to amino acid-based formula 8
• Rice protein-based eHF can be an alternative to cow milk protein-based eHF 8
• Soy formula is NOT recommended as first-line due to 20-40% cross-reactivity risk 5, but can be considered for infants >6 months after establishing tolerance by clinical challenge 8
• Goat's milk and sheep's milk are NOT suitable alternatives due to high protein homology with cow's milk 6

Timeline and Monitoring

• Most infants return to usual health within 3-10 days of switching to hypoallergenic formula or maternal elimination diet, with median resolution time of 5 days 5
• The elimination diet should be strictly followed for at least 9-12 months 8
• In severe cases, temporary bowel rest and intravenous fluids may be necessary, with 90% success rate 5

Reintroduction Protocol

Oral food challenge should be performed at 9-12 months of age in a hospital setting to assess tolerance development, with reintroduction attempted under medical supervision typically after 6-12 months of elimination. 5, 6, 8

• The timing varies based on severity of initial symptoms and type of CMPA (IgE-mediated tends to be more persistent) 8
• Some children will tolerate only limited daily amounts of cow milk protein initially 8
• Repeated exposure to cow milk protein appears to facilitate acquisition of tolerance 8
• 80% of infants acquire tolerance before age 3-4 years 2

Critical Pitfalls to Avoid

• Do not discontinue breastfeeding prematurely when maternal elimination diet can effectively manage symptoms 6
• Do not use soy formula as first-line alternative in infants under 6 months 5, 8
• Do not perform unnecessary maternal dietary restrictions beyond confirmed allergens, as this compromises maternal nutrition 5, 6
• Do not delay diagnosis by over-relying on laboratory testing in non-IgE mediated cases 3
• Children with cow milk or soy-induced FPIES have 30% likelihood of reacting to solid foods, most commonly rice or oat 5