title: Randomized feeding intervention in infants at high risk for celiac disease.
abstract: BACKGROUND
  A 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  Celiac 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.
  
  
  CONCLUSIONS
  As 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.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: Sabine L
authors.initials: SL
authors.lastname: Vriezinga
authors.forename: Renata
authors.initials: R
authors.lastname: Auricchio
authors.forename: Enzo
authors.initials: E
authors.lastname: Bravi
authors.forename: Gemma
authors.initials: G
authors.lastname: Castillejo
authors.forename: Anna
authors.initials: A
authors.lastname: Chmielewska
authors.forename: Paula
authors.initials: P
authors.lastname: Crespo Escobar
authors.forename: Sanja
authors.initials: S
authors.lastname: Kolaček
authors.forename: Sibylle
authors.initials: S
authors.lastname: Koletzko
authors.forename: Ilma R
authors.initials: IR
authors.lastname: Korponay-Szabo
authors.forename: Eckart
authors.initials: E
authors.lastname: Mummert
authors.forename: Isabel
authors.initials: I
authors.lastname: Polanco
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.forename: Carmen
authors.initials: C
authors.lastname: Ribes-Koninckx
authors.forename: Raanan
authors.initials: R
authors.lastname: Shamir
authors.forename: Hania
authors.initials: H
authors.lastname: Szajewska
authors.forename: Katharina
authors.initials: K
authors.lastname: Werkstetter
authors.forename: Luigi
authors.initials: L
authors.lastname: Greco
authors.forename: Judit
authors.initials: J
authors.lastname: Gyimesi
authors.forename: Corina
authors.initials: C
authors.lastname: Hartman
authors.forename: Caroline
authors.initials: C
authors.lastname: Hogen Esch
authors.forename: Erica
authors.initials: E
authors.lastname: Hopman
authors.forename: Anneli
authors.initials: A
authors.lastname: Ivarsson
authors.forename: Tunde
authors.initials: T
authors.lastname: Koltai
authors.forename: Frits
authors.initials: F
authors.lastname: Koning
authors.forename: Eva
authors.initials: E
authors.lastname: Martinez-Ojinaga
authors.forename: Chantal
authors.initials: C
authors.lastname: te Marvelde
authors.forename: Ana
authors.initials: A
authors.lastname: Pavic
authors.forename: Jihane
authors.initials: J
authors.lastname: Romanos
authors.forename: Els
authors.initials: E
authors.lastname: Stoopman
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Villanacci
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Ricardo
authors.initials: R
authors.lastname: Troncone
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Mearin
mesh_terms: D001323:Autoantibodies / Q000097:blood; D001706:Biopsy; D001942:Breast Feeding; D002446:Celiac Disease / Q000175:diagnosis / Q000235:genetics / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D004032:Diet; D004044:Dietary Proteins / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology; D005838:Genotype; D005903:Gliadin / Q000276:immunology; D005983:Glutens / Q000008:administration & dosage*; D006683:HLA-DQ Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D007421:Intestine, Small / Q000473:pathology; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012306:Risk; D011503:Transglutaminases / Q000276:immunology
chemical_list: D001323:Autoantibodies; D004044:Dietary Proteins; D006683:HLA-DQ Antigens; D005983:Glutens; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins