While gluten (the protein in flour which gives the dough elasticity and strength) ingestion is responsible for the signs and symptoms of celiac disease, it is not known what factors are associated with initial appearance of the disease.

As a result, a study, published in the Journal of the American Medical Association 2005;293:2343-2351, was performed to examine whether the timing of gluten exposure in the infant diet was associated with the development of celiac disease autoimmunity (CDA). The investigation was based on a prospective observational study conducted in Denver, CO, from 1994-2004 of 1,560 children at increased risk for celiac disease or type 1 diabetes. The increased risk was defined by possession of either HLA-DR3 or DR4 alleles, or having a first-degree relative with type 1 diabetes. The mean follow-up was 4.8 years.

The main outcome measure was risk of CDA, as defined as either:

1) being positive for tissue transglutaminase (tTG) autoantibody on 2 or more consecutive visits, or

2) being positive for tTG once and having a positive small bowel biopsy for celiac disease, in relation to the timing of introduction of gluten-containing foods into the diet.

During the study, 51 children developed CDA. Findings adjusted for HLA-DR3 status indicated that children exposed to foods containing wheat, barley, or rye (gluten-containing foods) in the first 3 months of life had a 5-fold increased risk of CDA compared with children exposed to gluten-containing foods at 4 to 6 months (hazard ratio [HR], 5.17.

Children not exposed to gluten until the seventh month or later had a marginally increased risk of CDA compared with those exposed at 4 to 6 months (HR, 1.87. After restricting the case group to only the 25 CDA-positive children who had biopsy-diagnosed celiac disease, initial exposure to wheat, barley, or rye in the first 3 months or in the seventh month or later significantly increased risk of CDA compared with exposure at 4 to 6 months (HR, 22.97, P = .001; and HR, 3.98, P = .04, respectively).

According to the authors, timing of introduction of gluten into the infant diet is associated with the appearance of CDA in children at increased risk for the disease.