• Sabine L Vriezinga, Renata Auricchio, Enzo Bravi, Gemma Castillejo, Anna Chmielewska, Paula Crespo Escobar, Sanja Kolaček, Sibylle Koletzko, Ilma R Korponay-Szabo, Eckart Mummert, Isabel Polanco, Hein Putter, Carmen Ribes-Koninckx, Raanan Shamir, Hania Szajewska, Katharina Werkstetter, Luigi Greco, Judit Gyimesi, Corina Hartman, Caroline Hogen Esch, Erica Hopman, Anneli Ivarsson, Tunde Koltai, Frits Koning, Eva Martinez-Ojinaga, Chantal te Marvelde, Ana Pavic, Jihane Romanos, Els Stoopman, Vincenzo Villanacci, Cisca Wijmenga, Ricardo Troncone, and M Luisa Mearin.
• The authors' affiliations are listed in the Appendix.
• N. Engl. J. Med. 2014 Oct 2; 371 (14): 1304-15.

BackgroundA window of opportunity has been suggested for reducing the risk of celiac disease by introducing gluten to infants at 4 to 6 months of age.MethodsWe performed a multicenter, randomized, double-blind, placebo-controlled dietary-intervention study involving 944 children who were positive for HLA-DQ2 or HLA-DQ8 and had at least one first-degree relative with celiac disease. From 16 to 24 weeks of age, 475 participants received 100 mg of immunologically active gluten daily, and 469 received placebo. Anti-transglutaminase type 2 and antigliadin antibodies were periodically measured. The primary outcome was the frequency of biopsy-confirmed celiac disease at 3 years of age.ResultsCeliac disease was confirmed by means of biopsies in 77 children. To avoid underestimation of the frequency of celiac disease, 3 additional children who received a diagnosis of celiac disease according to the 2012 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition diagnostic criteria (without having undergone biopsies) were included in the analyses (80 children; median age, 2.8 years; 59% were girls). The cumulative incidence of celiac disease among patients 3 years of age was 5.2% (95% confidence interval [CI], 3.6 to 6.8), with similar rates in the gluten group and the placebo group (5.9% [95% CI, 3.7 to 8.1] and 4.5% [95% CI, 2.5 to 6.5], respectively; hazard ratio in the gluten group, 1.23; 95% CI, 0.79 to 1.91). Rates of elevated levels of anti-transglutaminase type 2 and antigliadin antibodies were also similar in the two study groups (7.0% [95% CI, 4.7 to 9.4] in the gluten group and 5.7% [95% CI, 3.5 to 7.9] in the placebo group; hazard ratio, 1.14; 95% CI, 0.76 to 1.73). Breast-feeding, regardless of whether it was exclusive or whether it was ongoing during gluten introduction, did not significantly influence the development of celiac disease or the effect of the intervention.ConclusionsAs compared with placebo, the introduction of small quantities of gluten at 16 to 24 weeks of age did not reduce the risk of celiac disease by 3 years of age in this group of high-risk children. (Funded by the European Commission and others; PreventCD Current Controlled Trials number, ISRCTN74582487.).

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