Diagnosis and management of non-IgE-mediated cow's milk allergy in infancy—a UK primary care practical guide

Venter, Brown, Shah, Walsh and Fox

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History taking

  • Taking an allergy-focused history forms the cornerstone of the diagnosis of food allergies including cow’s milk allergy (CMA), and the UK NICE clinical guideline (CG) 116 Diagnosis and assessment of food allergy in children and young people in primary care and community settings recommends that questions should be asked regarding:
    • any family history of atopic disease in parents or siblings
    • any personal history of early atopic disease
    • the infant’s feeding history
    • presenting symptoms and signs that may be indicating possible CMA
    • details of previous management, including any medication and the perceived response to any management
    • was there any attempt to change the diet and what was the outcome?
  • Following on from these questions, the next important step is to attempt to differentiate between possible IgE and non-IgE-mediated allergies (see first algorithm) and decide which tests to do

IgE-mediated CMA

  • For the diagnosis of IgE-mediated CMA, the use of skin prick tests (SPT) or serum-specific IgE tests are recommended, but these should only be performed by those competent to interpret the tests

Suspected cow’s milk allergy in the first year of life—having taken an allergy-focused clinical history

Cow's milk allergy in the first year of life

Non-IgE-mediated CMA

  • There are no validated tests for the diagnosis of non-IgE CMA, apart from the planned avoidance of cow’s milk and cow’s milk containing foods, followed by reintroduction as a home challenge to confirm the diagnosis
  • Home reintroduction/challenges may not be acceptable in children with severe forms of non-IgE-mediated CMA, and these children should be referred to secondary/tertiary care

The role of dietary interventions in the diagnosis of IgE and non-IgE-mediated CMA

  • Maternal avoidance of cow’s milk in the case of breast fed infants, or choosing an appropriate formula for bottle fed/partially bottle fed infants are crucial steps in the diagnosis of CMA. Mothers excluding cow’s milk from their diet should be supplemented with calcium and vitamin D
  • Choosing the most appropriate formula (see second algorithm, below) should be based on clinical presentation, the nutritional composition, and residual allergenicity of the proposed hypoallergenic formula
  • Breast-feeding is always the preferred way to feed any infant. In any case where there is a need to exclude cow’s milk from the maternal diet and a top-up formula is needed, a systematic review suggests that an animo acid-based formula may be of benefit
  • An amino acid-based formula is recommended as a first line of treatment for those infants with a history of anaphylaxis to cow’s milk, Heiner Syndrome, eosinophilic eosophagitis, and severe gastro-intestinal and/or skin presentations, particularly in association with faltering growth
  • Extensively hydrolysed formula (eHF) is recommended as a first line of choice for infants with mild to moderate presentations of CMA, e.g. colic, reflux, diarrhoea, vomiting, or eczema in the absence of faltering growth. eHF containing whey may not be suitable as a first line of treatment of those infants with possible secondary lactose intolerance
  • Soya formula can be used in infants over 6 months of age who do not tolerate the eHF, particularly if they are suffering from IgE mediated CMA in the absence of sensitisation to soya

Primary care management of mild to moderate non-IgE-mediated cow’s milk allergy (no initial IgE skin prick tests or serum-specific IgE assays necessary)

Primary care management of mild to moderate non-IgE cow's milk allergy

Role of the dietitian

  • Dietitians can give invaluable advice regarding the level of cow’s milk allergen avoidance that is required i.e., which foods should be omitted and which foods can be tolerated
  • The role of the dietitian is also to provide written information on suitable substitute foods, recipes, online information, label reading, and lifestyle adjustments
  • Finally, the dietitian plays a central role in organising/designing food challenges to diagnose CMA and determine development of tolerance

Determining development of tolerance to cow’s milk

  • There is no ideal time for testing for development of tolerance, but it is generally accepted that infants with a proven CMA diagnosis should remain on a cow’s milk protein-free diet until 9–12 months of age and for at least 6 months prior to reintroduction of cow’s milk into their diets
  • Hospital challenge or onward referral to secondary/tertiary care should be considered (see first algorithm, page 1) if either of the following is true:
    • there has ever been suspicion of an acute onset of symptoms following ingestion
    • current atopic eczema and positive serum-specific IgE for cow’s milk protein
  • The NICE UK food allergy guideline (NICE CG116) states that no child with IgE-mediated food allergy should have a food challenge in primary care or community settings. All those remaining children diagnosed as mild-moderate non-IgE-mediated CMA are suitable for a home challenge. Guidance on how to perform both the initial home challenge to confirm diagnosis, and the later planned home reintroduction to confirm acquired tolerance using a milk ladder, is given at www.ctajournal.com/content/3/1/23/additional


  • Diagnosis and management of non-IgE-mediated CMA can take place in primary care; however, all infants on a cow’s milk exclusion diet should ideally be referred to a dietitian, preferably before weaning onto solid food takes place. Referral to secondary care should be made as per the proposed algorithms, adapted from NICE CG116


full guidelines available from…

Venter et al. Clinical and Translational Allergy 2013, 3: 23.
First included: Sep 13.

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