Cow's milk protein intolerance

Pre-referral guidelines for primary care providers

Cow’s milk protein intolerance (CMPI) is a common condition, found in 2-3% of infants. There is a frequent (up to 30%) cross-reactivity with soy. It may present as an allergic procto-colitis or an enteropathy, or less commonly, FPIES (food protein induced enterocolitis syndrome). It may manifest in both breast-fed and artificial formula fed babies.

Over 50% of children will have outgrown CMPI by 12 months, and over 80% by three years of age.

CMPI may be either IgE or non-IgE mediated, although is more commonly the latter, and very seldomly presents with sudden onset anaphylactic symptoms or signs.

Diagnosis

The diagnosis of CMPI is largely clinical, although is assisted by simple elimination trials.

Symptoms commonly seen in cow’s milk protein intolerance include irritability, poor sleep, vomiting, diarrhoea or constipation, eczema, failure to thrive, haematochezia (blood in stool) and mucousy stools

Diagnosis will be supported by an elimination trial (see management below) using either a single-blind trial (quick and easy) or the gold standard double-blind placebo controlled trial (not usually required in CMPI). Skin prick testing or RAST is generally not indicated in the diagnosis or management of CMPI as it is more commonly a non-IgE mediated intolerance.

Differentials

  • Infant irritability may reflect many underlying difficulties and does not, on its own, diagnose CMPI (see Irritable infant for further details).
  • Primary lactose intolerance is an exceedingly rare condition associated with marked difficulty breast feeding (a large source of lactose) as well as neurological difficulties and developmental delay.
  • Secondary lactose intolerance, which is due to damage to the gut brush border, is generally due to either CMPI or rotavirus gastroenteritis, and is a self-limiting transient phenomenon. Thus , although a lactose-free formula may lead to symptomatic relief with CMPI, the underlying problem still exists.
  • Acquired lactose intolerance is a genetically determined intolerance that develops later in life (generally from adolescence or later) and is more common in certain racial groups such as Africans and Asians.

Practice points

  • Cow’s milk protein intolerance (CMPI) is common and should not be confused with lactose intolerance (see diagnosis above)
  • Exclusion trials are generally required to support a diagnosis of CMPI
  • There is no role for the use of allergy testing in the diagnosis or management of simple CMPI
  • There is evidence to support the recommendation of using hypoallergenic or partially hydrolysed ('HA') formula in the prevention of CMPI in those infants with a family history of a first degree relative with atopic disease.
  • There is no role for the use of lactose free ('LF'), anti-reflux ('AR') or hypoallergenic/partially hydrolysed ('HA') formula in the management of CMPI, nor is goat’s milk or other animal milk a suitable alternative to cow’s milk.
  • Soy formula is not recommended for the prevention of CMPI in children under four months of age.
  • Extensively hydrolyzed formula (e.g. Pepti-junior, Alfare) and elemental/amino acid formula (e.g. Neocate, Elecare) both require specialist consultation to prescribe.

Management

Elimination trial

An elimination trial is generally recommended for diagnosis of CMPI.

For breast fed babies, the mother should strictly exclude all cow’s milk protein (i.e. all dairy, including milk solids) and soy for 2-3 weeks. She should be given a calcium supplement during this time (1200mg daily). After the exclusion period, she should restart dairy and symptoms are expected to return within 2-3 days.

For formula fed babies, a trial of an extensively hydrolyzed formula (eHf) is required

  • Peptijunior, Alfare and Alfamino are authority prescription eHf that require paediatrician consultation or discussion prior. They can be purchased over-the-counter, although are very expensive compared with conventional formula.
  • Aller-pro is a new eHf that is available over-the-counter and is more affordable (approx. $28 per 900g tin). The only difference is that Aller-pro does still contain lactose, thus if there is a secondary lactose intolerance there may be a clouding of response to an elimination trial in the first instance.
  • For formula fed babies who do not respond to a trial of eHf, who have persisting symptoms suggestive of CMPI, an elemental or completely hydrolyzed formula (e.g. Neocate, Elecare) may be trialled after consultation with a paediatric gastroenterologist, specialist allergist or immunologist.

Ongoing management

A diagnosis of CMPI made after an elimination trial requires ongoing avoidance of cow’s milk protein (dairy) and most likely soy. This can either be achieved through a sustained exclusion diet by the mother for breast-fed babies, or ongoing use of an extensively hydrolyzed formula (or elemental formula) for formula fed babies, as detailed above.

Recommendation is then for a gradual introduction of cow’s milk containing cheese and yoghurts from 6-8 months, then building these up before introducing cow’s milk from 12 months of age. Soy can be trialled in children over 6 months of age, or when the introduction of cow’s milk products continues to produce symptoms of CMPI.

Referral pathways

  • Paediatrician
    • A referral to paediatric outpatient services is recommended when there is a high suspicion of CMPI, or if an elimination trial using an extensively hydrolyzed formula is being undertaken.