[Skip to Content]
[Skip to Content Landing]
Views 4,048
Citations 0
Original Investigation
September 28, 2020

Early Gluten Introduction and Celiac Disease in the EAT Study: A Prespecified Analysis of the EAT Randomized Clinical Trial

Author Affiliations
  • 1The Paediatric Allergy Research Group, Department of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, United Kingdom
  • 2The Population Health Research Institute, St George's, University of London, London, United Kingdom
  • 3The St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospital NHS Foundation Trust, London, United Kingdom
  • 4Benaroya Research Institute, Seattle, Washington
JAMA Pediatr. Published online September 28, 2020. doi:10.1001/jamapediatrics.2020.2893
Key Points

Question  Is early introduction of gluten associated with a reduced prevalence of celiac disease at age 3 years?

Findings  In this prespecified analysis of a randomized clinical trial, the mean quantities of gluten consumed in an early introduction group between age 4 and 6 months was 2.66 g/wk and 0.49 g/wk in a standard introduction group that did not receive gluten until at least age 6 months. Significantly more children in the standard introduction group had a diagnosis of celiac disease confirmed than in the early introduction group (1.4% vs 0%).

Meaning  The findings of this trial indicate that early consumption of high-dose gluten should be considered as a strategy to prevent celiac disease in future research.


Importance  There are no strategies for the prevention of celiac disease (CD). Current guidelines stating that the age at gluten introduction does not affect the prevalence of CD are based on the results from several randomized clinical trials, but the doses of gluten and timing of its introduction varied.

Objective  To determine whether early introduction of high-dose gluten lowers the prevalence of CD at age 3 years.

Design, Setting, and Participants  The Enquiring About Tolerance (EAT) Study was an open-label randomized clinical trial. A total of 1303 children from the general population in England and Wales were recruited and followed up from November 2, 2009, to July 30, 2012. For the present study, samples were collected from November 1, 2012, to March 31, 2015, and data were analyzed from April 25, 2017, to September 17, 2018.

Interventions  Infants were randomized to consume 6 allergenic foods (peanut, sesame, hen's egg, cow's milk, cod fish, and wheat) in addition to breast milk from age 4 months (early introduction group [EIG]) or to avoid allergenic foods and follow UK infant feeding recommendations of exclusive breastfeeding until approximately age 6 months (standard introduction group [SIG]).

Main Outcomes and Measures  Evaluation of CD was an a priori secondary end point of the EAT Study, and at age 3 years, all children with available serum samples were tested for antitransglutaminase type 2 antibodies. Children with antibody levels greater than 20 IU/L were referred to independent gastroenterologists for further investigation.

Results  Of the 1004 infants included in the analysis, 514 were male (51.2%). The mean (SD) quantity of gluten consumed between ages 4 and 6 months was 0.49 (1.40) g/wk in the SIG and 2.66 (1.85) g/wk in the EIG (P < .001). Mean (SD) weekly gluten consumption ranged from 0.08 (1.00) g/wk at age 4 months to 0.9 (2.05) g/wk at age 6 months in the SIG vs 1.3 (1.54) g/wk at age 4 months to 4.03 (2.40) g/wk at age 6 months in the EIG. Seven of 516 children from the SIG (1.4%) had a diagnosis of CD confirmed vs none of the 488 children in the EIG (P = .02, risk difference between the groups using the bootstrap, 1.4%; 95% CI, 0.6%-2.6%).

Conclusions and Relevance  In this analysis of infants in the EAT Study, the introduction of gluten from age 4 months was associated with reduced CD prevalence. These results suggest that early high-dose consumption of gluten should be considered as a strategy to prevent CD in future studies.

Trial Registration  isrctn.org Identifier: ISRCTN14254740

Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words