Randomized feeding intervention in infants at high risk for celiac disease

N Engl J Med. 2014 Oct 2;371(14):1304-15. doi: 10.1056/NEJMoa1404172.

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.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / blood
  • Biopsy
  • Breast Feeding
  • Celiac Disease / diagnosis
  • Celiac Disease / genetics
  • Celiac Disease / prevention & control*
  • Child
  • Child, Preschool
  • Diet*
  • Dietary Proteins / administration & dosage*
  • Double-Blind Method
  • Female
  • GTP-Binding Proteins / immunology
  • Genotype
  • Gliadin / immunology
  • Glutens / administration & dosage*
  • HLA-DQ Antigens / genetics
  • Humans
  • Infant
  • Intestine, Small / pathology
  • Male
  • Proportional Hazards Models
  • Prospective Studies
  • Risk
  • Transglutaminases / immunology

Substances

  • Autoantibodies
  • Dietary Proteins
  • HLA-DQ Antigens
  • Glutens
  • Gliadin
  • transglutaminase 2
  • Transglutaminases
  • GTP-Binding Proteins

Associated data

  • ISRCTN/ISRCTN74582487