cow's milk protein allergy (CMPA)

Last edited 03/2020 and last reviewed 09/2020

Cow's milk protein allergy (CMPA)

Cow's milk protein allergy/cows' milk allergy

  • defined as adverse reactions to cow's milk that can be reproduced and are immune-mediated (1,2,3,4,5,6)
    • are immunoglobulin E (IgE)-mediated, cell-mediated (non-IgE), or the combination of the two

  • estimated that up to 4.9% of children suffer from cow’s milk protein allergy (CMPA) (5)

  • CMPA has previously been termed cow's milk protein intolerance (CMPI) (7)

CMPA - General features:

  • estimated that fifty to sixty per cent of affected children have skin symptoms and/ or gastrointestinal symptoms and 20-30% have respiratory symptoms (4)
  • CMPA may be the underlying cause of gastro-oesophageal reflux disease (GORD) in up to 40% of infants and young children (4)
  • CMPA will resolve in 40-50% of infants by 1 year, 60-75% by 2 years and 85-90% by 3 years (4)
    • however the natural history is actively changing, showing a definite trend to persist longer, especially the IgE-mediated clinical expression of CMPA (4)
  • only about 10% of babies with CMPA will require an amino acid formula (AAF). The remainder should tolerate an extensively hydrolysed formula (EHF) (6)
    • 10-14% of infant with CMPA will also react to soya proteins (and up to 50% of those with non-IgE mediated CMPA). But because of better palatability soya formula is worth considering in babies>6months (6)

IgE mediated allergic reaction to milk protein

  • IgE-mediated reactions typically occur immediately after ingestion
  • IgE-mediated reactions are immediate, requiring only a small quantity of food to be ingested, enabling rapid identification of the allergenic foods
  • - involve the production of specific IgE antibody protein molecules directed against the food protein. It is a well defined mechanism, which is relatively easy to diagnose using a combination of clinical history and validated tests such as skin prick tests and specific IgE’s

Non-IgE mediated allergic reaction to milk protein

  • non-IgE mediated are delayed and take up to 72 hours to develop, but still involve the immune system (4) - therefore the identification of suspect foods is often difficult. The mechanism is unclear, it is harder to diagnose and there are no validated tests to confirm such an allergic reaction
  • symptoms of non-IgE mediated disease are commonly wrongly labelled as symptoms of intolerance, using either the terms 'lactose intolerance' or 'milk intolerance' (2)


  • soya is not recommended before 6 months of age due to it containing isoflavones, which may exert a weak oestrogenic effect. There is also a risk of cross-reactivity: up to 14% of those with IgE-mediated cow’s milk allergy also react to soya and up to 60% of those with non-IgE-mediated cow’s milk allergy
  • rice milk is not recommended in those aged <4.5 years due to the arsenic content; and there is cross-reaction between mammalian milks
  • goat’s milk and products are not suitable for infants with cow’s milk allergy


  • NICE. Food allergy in children and young people: diagnosis and assessment of food allergy in children and young people in primary care and community settings. CG 116. 2011
  • Walsh J et al. Differentiating milk allergy (IgE and non-IgE mediated) from lactose intolerance: understanding the underlying mechanisms and presentations. Br J Gen Pract 2016; DOI: 10.3399/bjgp16X686521
  • Ludman S, Shah N, Fox AT. Managing cow's milk allergy in children. BMJ 2013; 347: f5424.
  • NHS Fife. Diagnosis and Management of Infants with Suspected Cow’s Milk Protein Allergy. A guide for healthcare professionals working in primary care (Accessed 8/3/2020)
  • Fiocchi A, Brozek J, Schunemann H, Bahna SL, Von BA, Beyer K et al: World Allergy Organisation (WAO) diagnosis and rationale for action against Cow’s milk allergy (DRACMA) guidelines. World Allergy Organ J 2010
  • Wessex Infant Feeding Guidelines and Appropriate Prescribing of Specialist Infant Formulae (Accessed 8/3/2020).
  • Ewing WM, Allen PJ. The diagnosis and management of cow milk protein intolerance in the primary care setting.Pediatr Nurs 2005;31(6):486-93