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

Research output: Contribution to journalArticlepeer-review

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

Original languageEnglish
Pages (from-to)82-93
Number of pages12
JournalClinical and Experimental Allergy
Issue number1
Early online date7 Dec 2021
Accepted/In press2021
E-pub ahead of print7 Dec 2021
PublishedJan 2022

Bibliographical note

Funding Information: All authors have completed the ICMJE uniform disclosure form at and declare: Professor Lack reports grants from UK Food Standards Agency, grants from Medical Research Council, other from MRC & Asthma UK Centre, other from UK Dept of Health through NIHR, other from National Peanut Board, during the conduct of the study; personal fees and other from DBV Technologies, other from Mighty Mission Me, personal fees from Novartis, personal fees from Sanofi‐Genyzme, personal fees from Regeneron, personal fees from ALK‐Abello, personal fees and other from Lurie Children's Hospital, outside the submitted work; Dr Vincent reports a grant from International Society of Atopic Dermatitis (ISAD), a three‐month research fellowship award granted to Rosie Vincent (10000 euro bursary from Pfizer) and support from NIHR School for Primary Care Research, during the conduct of the study; Dr Radulovic reports grants from Food Standard Agency and MRC, during the conduct of the study; Dr Marrs reports other from Sponsorship of a Post‐Graduate Allergy Teaching Institute, which included manufacturers of hypoallergenic formula milk amongst others until their sponsorship was terminated in Summer 2019, outside the submitted work. Dr Flohr, Dr Perkin, Dr Logan, Dr MacNeill, Dr Craven and Dr Ridd have nothing to disclose. Funding Information: RV was funded by a three‐month International Society of Atopic Dermatitis (ISAD) Research Fellowship. The sponsor of this award, Pfizer, have not had any input into the design or reporting of this study. The study was also supported by NIHR School for Primary Care Research. Publisher Copyright: © 2021 John Wiley & Sons Ltd

King's Authors


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.

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