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Am Fam Physician. 2021;103(10):631

Clinical Question

Does introducing gluten to exclusively breastfed infants at four months of age, compared with six months of age, reduce the prevalence of celiac disease in the first three years of life?

Bottom Line

The introduction of dietary allergens, including gluten, to exclusively breastfed infants at four months of age, compared with six months of age, delays the prevalence of celiac disease at three years of age. (Level of Evidence = 2b)


The Enquiring About Tolerance study was an open-label trial that randomized exclusively breastfed infants in Wales and England to receive dietary allergens at four months of age (early introduction; n = 652) or at six months of age (control; n = 651). The dietary allergens included cow's milk, hen's eggs, peanuts, sesame, cod fish, and wheat. In this component of the study, the researchers gave two wheat-based biscuits (4 g of wheat; 3.2 g of gluten) every week to the infants randomized to early gluten introduction. During the three years of follow-up, the parents were asked to complete dietary questionnaires at various intervals. All study participants were tested for antitransglutaminase type 2 antibodies and those with abnormal values were referred to gastroenterologists for final diagnosis. During the follow-up period, 72 infants were lost to follow-up (7% of the early introduction group and 4% of the control group) and an additional 15% in each group had either no blood drawn or an insufficient quantity of blood drawn. By three years of age, nine children, six of whom had symptoms attributable to celiac disease, had elevated antitransglutaminase type 2 antibodies and were referred to gastroenterologists. Three of the children had biopsies, two of which confirmed celiac disease. Six of the symptomatic children improved after being fed gluten-free diets. The authors concluded that none of the children in the early introduction group had celiac disease compared with seven children (1.4%) in the control group (number needed to treat = 72; 95% CI, 39 to 167).

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Uncertain

Setting: Population-based

Reference: Logan K, Perkin MR, Marrs T, et al. Early gluten introduction and celiac disease in the EAT study: a prespecified analysis of the EAT randomized clinical trial. JAMA Pediatr. 2020;174(11):1041–1047.

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