Early introduction of gluten may prevent coeliac disease in children

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Introducing high doses of gluten from four months of age into infants’ diets could prevent them from developing coeliac disease, a study has found. These results from the Enquiring About Tolerance (EAT) Study by researchers from King’s Guy’s and St Thomas’ NHS Foundation Trust, St George’s, University of London, and Benaroya Research Institute-Seattle, suggest the early introduction of high-dose gluten may be an effective prevention strategy for the disease, though researchers say further studies are needed before being applied in practice.

Coeliac disease is an autoimmune disease whereby eating gluten causes the body’s immune system to attack its own tissues. There are currently no strategies to prevent coeliac disease and treatment involves long-term exclusion of gluten from the diet. Even very small amounts of gluten in the diet of those with coeliac disease can cause damage to the lining of the gut, prevent proper absorption of food and result in symptoms including bloating, vomiting, diarrhoea, constipation, and tiredness.

Previous studies exploring early introduction of gluten in infants have varied in the amount of gluten consumed and the timing of the introduction. The EAT study investigated the effects of gluten alongside breastfeeding, from the age of four months. The results were compared to children who avoided allergenic foods and consumed only breast milk until age six months as per UK government guidelines.

Infants in the intervention arm of the EAT study were given 4g of wheat protein a week from four months of age. This was in the form of two wheat-based cereal biscuits such as Weetabix, representing an age-appropriate portion of wheat.

1004 children were tested for anti-transglutanimase antibodies, an indicator of coeliac disease, at three years of age. Those with raised antibody levels were referred for further testing by a specialist.

The results showed that among children who delayed gluten introduction until after six months of age, the prevalence of coeliac disease at three years of age was higher than expected – 1.4% of this group of 516 children. In contrast, among the 488 children who introduced gluten from four months of age, there were no cases of coeliac disease.

This is the first study that provides evidence that early introduction of significant amounts of wheat into a baby’s diet before six months of age may prevent the development of coeliac disease. This strategy may also have implications for other autoimmune diseases.

Lead author is Professor Gideon Lack, professor of paediatric allergy from the School of Life Course Sciences. Author Dr Kirsty Logan, researcher in paediatric allergy at King’s said: “Early introduction of gluten and its role in the prevention of coeliac disease should be explored further, using the results of the EAT Study as the basis for larger clinical trials to definitively answer this question.”

Abstract
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.

Authors
Kirsty Logan; Michael, R Perkin; Tom Marrs; Suzana Radulovic; Joanna Craven; Carsten Flohr; Henry T Bahnson; Gideon Lack

 

Kings College London material

 

JAMA Pediatrics abstract

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