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Cow’s Milk Protein Allergy (CMPA) : Diagnosis and Management

Cow’s milk protein allergy (CMPA) is one of the most common food allergies reported in infants and children, and is estimated to have a prevalence of 2-7.5% in the U.K¹ and Europe². CMPA typically presents in early infancy, often at the time of initial exposure to cow’s milk protein (CMP) formula or introduction of CMP containing solids. Whilst CMPA can present in exclusively breastfed infants, the incidence is much lower at 0.5%³. The majority of children will outgrow CMPA, in the past it was predicted that 85% outgrew it by 3 years, but more recent studies suggest this may take longer⁴.

CMPA results from an immunological reaction to one or more milk proteins, with ingestion of CMP causing a wide spectrum of symptoms (see table I). If the reaction involves immunoglobulin-E (IgE) it is described as IgE-mediated, or classic food allergy, with symptoms generally occurring within minutes. Reactions involving the immune system but not IgE antibodies are described as non-IgE-mediated allergy⁵. These reactions are usually delayed (24-48 hours) typically affecting the skin or gastrointestinal tract.

Diagnosis
The gold standard for diagnosis is resolution of symptoms when CMP is eliminated from the diet and their return when it is reintroduced. This is however not always appropriate, especially for those with immediate severe symptoms. In IgE-mediated allergy skin pricks tests and/or specific IgE blood tests aid diagnosis⁶. Patch testing for delayed hypersensitvity is possible but is time consuming requiring 3 clinic visits and so is not commonly performed. Thus a detailed clinical history and confirmation by CMP exclusion and reintroduction is the currently the major way of diagnosing non-IgE-mediated CMPA.

Management
In 2007 new guidelines for the management of CMPA were published by an international panel of experts². These provide algorithms for breastfed and formula-fed infants and distinguish between the severity of symptoms. There are currently no consensus guidelines specifically for the UK.

Advice on alternative formulas, milk substitutes and milk-free weaning is an essential component of management of CMPA. Assessment of growth, symptoms, and nutritional intake should be undertaken at regular intervals with the prime aim being to ensure nutritional needs are met whilst remaining symptom free.

Breastfeeding is clearly the preferred method of infant feeding and should be encouraged despite a diagnosis of CMPA⁷ as it is well tolerated by the majority of these infants³. However, if symptomatic, exclusively breastfed CMPA infants may benefit from a 2-4 week period of maternal CMP avoidance +/- egg avoidance², as proteins from the maternal diet e.g. ß-lactoglobulin3 can transfer to breast-milk, followed by CMP reintroduction to confirm diagnosis. For those bottle or mix-fed infants a hypoallergenic formula should be prescribed.

A hypoallergenic formula contains <1% of immunoreactive protein and is tolerated by 90% of infants with CMPA ^{8, 9}. The majority of CMPA infants are treated with Extensively Hydrolysed Formulas (EHF)¹. EHF protein is comprised of short peptides of molecular weight mostly < 1500 Daltons and free amino acids. EHF’s available vary in protein source, allergenicity, palatability, fat source, novel substrates and presence of lactose.

However, EHF’s possess residual allergenicity as they contain small amounts of milk proteins e.g. ß-lactoglobulin. Sensitive individuals may continue to experience symptoms on EHF’s, in which case an amino acid formula (AAF) is recommended⁷.  AAF’s are composed of free amino acids and are considered non-allergenic⁷. Others who may require AAF as their first line formula are those who experience symptoms on breastmilk, severe systemic reactions or severe atopic dermatitis¹⁰. AAF’s are more expensive than EHF and a cost/benefit ratio needs to be considered when recommending their use¹⁰. The choice of formula thus depends on multiple factors including degree of hydrolysis required, age, symptoms, growth, acceptance and cost. Palatability of hypoallergenic formula is often an issue in weaned/older infants as they have distinct taste. Acceptability can be improved by gradual introduction of the new formula and using a covered beaker.

Soya infant formulas (SIF) are not recommended as first line treatment, due to concerns regarding phytoestrogens and potential risk of cross-reactivity, particularly in infants <6 months ^11,12,13. After 6 months SIFs are useful alternatives when hypoallergenic formulas are refused and have advantages such as palatability and cost. Goat’s milk is not recommended in CMPA as there is close homology between cows and goats milk proteins and clinically significant cross–allergenicity has been observed. Other milks including off the shelf soya, rice, oat, almond and pea milks are not appropriate for children <18-24 months as a main drink, due to their lack of nutritional adequacy. Calcium and vitamin enriched varieties should be recommended for older children. Recent concerns have been raised because of the modest levels of arsenic found in Rice based milks thus should not be used ¹⁵.

Early diagnosis and appropriate nutritional management of CMPA can prevent repeated trips to doctors and dietitians, help to achieve good growth and maintain a good quality of life.

Rachel DeBoer,
Paediatric Allergy Dietitian
Guys & St Thomas’ Hospital, London

Contact

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