Frequency of guideline-defined cow's milk allergy symptoms in infants: Secondary analysis of EAT trial data

Rosie Vincent*, Stephanie J. MacNeill, Tom Marrs, Joanna Craven, Kirsty Logan, Carsten Flohr, Gideon Lack, Suzana Radulovic, Michael R. Perkin, Matthew J. Ridd

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


Background: Non-IgE-mediated Cow's Milk Allergy (CMA) has a prevalence of less than 1% in children. Guidelines developed to help non-specialists diagnose CMA may lead to misattribution of normal symptoms and contribute to overdiagnosis of CMA. We sought to establish the frequency of symptoms during infancy associated with non-IgE-mediated CMA, using the international Milk Allergy in Primary Care (iMAP) guideline as representative of CMA guidelines more generally. Method: Secondary analysis of the Enquiring About Tolerance (EAT) randomized controlled trial (ISRCTN 14254740; 1303 exclusively breastfed 3-month-old healthy infants). Key outcomes were ≥2 iMAP symptoms associated with ‘mild-moderate’ and ‘severe’ non-IgE-mediated CMA. Results: Whilst breastfeeding and parental atopy rates were higher than the general population, participants were otherwise similar to the population of England and Wales. Two or more non-IgE CMA symptoms were reported by 25% families for mild-moderate and 1.4% for severe symptoms each month between ages 3 and 12 months, peaking at 38% with ≥2 mild-moderate and 4.3% ≥2 severe symptoms at three months, when participants were not directly consuming cow's milk. 74% of participants reported ≥2 mild-moderate symptoms and 9% ≥2 severe symptoms in at least one month during this period. At six months there was no evidence of difference in the proportion of children with ≥2 symptoms between those consuming (29.5% mild-moderate, 1.8% severe) and not consuming cow's milk (35.3% mild-moderate, 2.2% severe). Mean monthly reporting of ≥2 symptoms was also no different between those with (15.8% mild-moderate, 1.1% severe) or without eczema at baseline (16.7% mild-moderate, 1.3% severe). Conclusions: Guideline-defined symptoms of non-IgE-mediated CMA are very common in infants. Guidelines may promote milk allergy overdiagnosis by labelling normal infant symptoms as possible milk allergy.

Original languageEnglish
Pages (from-to)82-93
Number of pages12
JournalClinical and Experimental Allergy
Issue number1
Early online date7 Dec 2021
Publication statusPublished - Jan 2022


  • atopic dermatitis
  • clinical immunology
  • epidemiology
  • food allergy
  • pediatrics


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