Norris JM, Barriga K, Hoffenberg EJ, Taki I, Miao D, Haas JE, Emery LM, Sokol, RJ, Erlich HA, Eisenbarth GS, Rewers M. (2005) JAMA. 293 2343-2351.
Context: While gluten 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.
Objective: To examine whether the timing of gluten exposure in the infant diet was associated with the development of celiac disease autoimmunity (CDA).
Design, Setting, and Patients: Prospective observational study conducted in Denver, Colo, from 1994-2004 of 1560 children at increased risk for celiac disease or type 1 diabetes, as 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.
Main Outcome Measure: Risk of CDA defined as being positive for tissue transglutaminase (tTG) autoantibody on 2 or more consecutive visits or being positive for tTG once and having a positive small bowel biopsy for celiac disease, by timing of introduction of gluten-containing foods into the diet.
Results: Fifty-one 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 (3 (6%)CDA positive vs 40 (3%) CDA negative) had a 5-fold increased risk of CDA compared with children exposed to gluten-containing foods at 4 to 6 months (12 (23%) CDA positive vs 574 (38%) CDA negative) (hazard ratio (HR), 5.17; 95% confidence interval (CI), 1.44-18.57).
Children not exposed to gluten until the seventh month or later (36 (71%) CDA positive vs 895 (59%) CDA negative) had a marginally increased risk of CDA compared with those exposed at 4 to 6 months (HR, 1.87; 95% CI, 0.97-3.60).
After restricting our 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 (3 (12%) CDA positive vs 40 (3%)CDA negative) or in the seventh month or later (19 (76%) CDA positive vs 912 (59%) CDA negative) significantly increased risk of CDA compared with exposure at 4 to 6 months (3 (12%) CDA positive vs 583 (38%) CDA negative) (HR, 22.97; 95% CI, 4.55-115.93; P = .001; and HR, 3.98; 95% CI, 1.18-13.46; P = .04, respectively).
Conclusion: Timing of introduction of gluten into the infant diet is associated with the appearance of CDA in children at increased risk for the disease.