Cow’s Milk Allergy: GP Guidelines are Driving Overdiagnosis

Dawn O'Shea

December 13, 2021

The findings of a new study suggest guidelines are driving overdiagnosis of cow’s milk allergy (CMA) in infants. The research found that the level of guideline-diagnosed CMA in the study cohort was significantly higher than the known prevalence of CMA in the general population.

The team of dermatologists, paediatric allergy specialists, and population health scientists, led by the University of Bristol, undertook a secondary analysis of infant data from the Enquiring About Tolerance (EAT) Study. They examined the prevalence of food allergy symptoms as set out in the 2019 international Milk Allergy in Primary Care (iMAP) guideline.

They found that three-quarters of infants in the cohort subgroup had two or more symptoms during the first year of life that guidelines say may indicate CMA, yet the condition is known to affect just 1 or 2 per 100 infants.

The EAT Trial

EAT is a population-based randomised controlled trial designed to investigate whether the early introduction of allergenic foods into an infant's diet reduced the risk of development of food allergy to that food. It included 1303 exclusively breastfed 3-month-old infants in England and Wales who were randomised at 13-17 weeks of age to a standard introduction group (SIG) or an early introduction group (EIG). EIG infants were exposed to six potentially allergenic foods alongside breastfeeding. SIG infants were encouraged to be exclusively breastfed until around 6 months.

Questionnaires on the infant's general health and consumption of the allergenic foods were completed by parents monthly until the child was 12 months old.

The researchers used the 2019 international Milk Allergy in Primary Care (iMAP) guideline to examine the presence of CMA-related symptoms. There is limited published data on how common and persistent the symptoms identified in iMAP are in healthy infants, and there is no published validation of the 2019 iMAP guidelines.

Prevalence of Guidelines-Stated CMA Symptoms

The data from EAT showed that, between 3 and 12 months, the mean monthly reporting of milk-related symptoms by EAT families was 2%. By age 3 years, 0.6% (7/1166) of participants were diagnosed with an IgE-mediated CMA - 0.7% in the SIG group (4/597) and 0.5% in the EIG group (3/569).

The proportion of infants with two or more iMAP mild-moderate symptoms in each month was highest at age 3 months (37.6%), when no infant was directly consuming cow's milk, and reduced over time, the lowest point being 14% at 11 months. Almost three-quarters (73.6%) of infants had two or more mild-moderate symptoms when aged between 3 and 12 months.

Compared with mild-moderate symptoms, the proportions of participants reporting severe symptoms were much lower, with abdominal pain having the highest point prevalence (13.1%) at 3 months.

Most symptoms had a monthly reported prevalence between 1-2%.

Mean monthly reporting of individual symptoms ranged from 0% (blood in stools) to 45.8% (reflux). The latter peaked at 3 months, with 78.1% of EAT infants fulfilling this criterion.

Colic, vomiting, and abdominal discomfort were reported most frequently at 3 months, decreasing with age. In contrast, food refusal and aversion increasing over the first year of life.

Formula Consumption

Thirty-three participants (20 SIG, 13 EIG) were given either extensively hydrolysed formula milk, (11 SIG, 7 EIG) or amino acid-based formula milk (9 SIG, 5 EIG), or both (1 SIG) for a median duration of 3 months.

The proportion of SIG infants with two or more severe symptoms at 6 months did not differ significantly between consumers and non-consumers of formula milk (1.8% versus 2.2%; P=0.76).

An average of 30% of 5-12-month-old infants consuming non-cow's milk formula were still being given dairy-based solids at the same time.

The iMAP guideline stresses that there is a risk of overdiagnosis if milk exclusion diets are not followed up with the diagnostic reintroduction of milk. Treatment-resistant symptoms are essential to the diagnosis of CMA.

However, previous research suggests that, in practice, re-challenge is infrequently undertaken. An audit of patients prescribed hydrolysed formula in 43 South East London general practices found that only 21% had undergone a home challenge to confirm the diagnosis of non-IgE-mediated CMA.


Hence, there is concern that normal symptoms of infancy are being medicalised. The "seed of suspicion" of a potential non-IgE-mediated CMA is likely to result in increasing prescriptions.

of unwarranted specialised formula milks and unvalidated allergy tests. In addition, the inference [SM1]  that cow’s milk protein can be transmitted through breast milk, might discourage mothers from breastfeeding.

"The over-perception of food allergy in the general public is long standing and precedes the emergence of milk allergy guidelines for both adults and children," the authors say. "However, guidelines that potentially exacerbate the problem of overdiagnosis are not helpful."

"There is an assumption that the existence of a guideline is more beneficial than no guideline. However, well-meaning guidelines need to be supported by robust data to avoid harms from overdiagnosis that exceed the damage of missed and delayed cow's milk allergy diagnoses that they are seeking to prevent."

Dr Rosie Vincent, honorary clinical research fellow at the Centre for Academic Primary Care at the University of Bristol who led the research, said [SM2] : "Guidelines, designed to help the non-specialist to diagnose cow’s milk allergy in infants may unintentionally medicalise normal infant symptoms and promote over-diagnosis of cow’s milk allergy."

Dr Michael Perkin, from the Population Health Research Institute at St George’s, University of London, added: "Our findings come against a background of rising prescription rates for specialist formula for children with cow’s milk allergy, which is completely out of proportion to how common we know the condition is. Parents of young infants are often seen in clinics, worried about a medical cause for their infant’s symptoms such as colic, bringing up milk or loose stools.

However, our research confirms that these symptoms are extremely common. In an otherwise healthy infant, an underlying cause is unlikely. Incorrectly attributing these symptoms to cow’s milk allergy is not only unhelpful, but it may also cause harm by discouraging breastfeeding."


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