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

JAMA Pediatr. 2020 Nov 1;174(11):1041-1047. doi: 10.1001/jamapediatrics.2020.2893.

Kirsty Logan 1, Michael R Perkin 2, Tom Marrs 1, Suzana Radulovic 1, Joanna Craven 1, Carsten Flohr 3, Henry T Bahnson 4, Gideon Lack 1


Author information

  • 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.


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.

© Copyright 2013-2021 GI Health Foundation. All rights reserved.
This site is maintained as an educational resource for US healthcare providers only. Use of this website is governed by the GIHF terms of use and privacy statement.