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Aronsson, C.A.* ; Lee, H.S.* ; Liu, E.* ; Uusitalo, U.* ; Hummel, S. ; Yang, J.* ; Hummel, M. ; Rewers, M.* ; She, J.X.* ; Simell, O.* ; Toppari, J.* ; Ziegler, A.-G. ; Krischer, J.* ; Virtanen, S.M.* ; Norris, J.M.* ; Agardh, D.* ; TEDDY Study Group (Beyerlein, A. ; Knopff, A. ; Peplow, C. ; Roth, R. ; Stock, J. ; Strauss, E. ; Warncke, K. ; Winkler, C.)

Age at gluten introduction and risk of celiac disease.

Pediatrics 135, 239-245 (2015)

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OBJECTIVES: The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children. METHODS: TEDDY (The Environmental Determinants of Diabetes in the Young) is a prospective birth cohort study. Newborn infants (N = 6436) screened for high-risk HLA-genotypes for CD were followed up in Finland, Germany, Sweden, and the United States. Information about infant feeding was collected at clinical visits every third month. The first outcome was persistent positive for tissue transglutaminase autoantibodies (tTGA), the marker for CD. The second outcome was CD, defined as either a diagnosis based on intestinal biopsy results or on persistently high levels of tTGA. RESULTS: Swedish children were introduced to gluten earlier (median: 21.7 weeks) compared with children from Finland (median: 26.1 weeks), Germany, and the United States (both median: 30.4 weeks) (P < .0001). During a median follow-up of 5.0 years (range: 1.7-8.8 years), 773 (12%) children developed tTGA and 307 (5%) developed CD. Swedish children were at increased risk for tTGA (hazard ratio: 1.74 [95% CI: 1.47-2.06]) and CD (hazard ratio: 1.76 [95% CI: 1.34-2.24]) compared with US children, respectively (P < .0001).Gluten introduction before 17 weeks or later than 26 weeks was not associated with increased risk for tTGA or CD, adjusted for country, HLA, gender, and family history of CD, neither in the overall analysis nor on a country-level comparison. CONCLUSIONS: In TEDDY, the time to first introduction to gluten introduction was not an independent risk factor for developing CD.

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