Introduction of gluten, HLA status, and the risk of celiac disease in children

N Engl J Med. 2014 Oct 2;371(14):1295-303. doi: 10.1056/NEJMoa1400697.

Abstract

Background: The relationship between the risk of celiac disease and both the age at which gluten is introduced to a child's diet and a child's early dietary pattern is unclear.

Methods: We randomly assigned 832 newborns who had a first-degree relative with celiac disease to the introduction of dietary gluten at 6 months (group A) or 12 months (group B). The HLA genotype was determined at 15 months of age, and serologic screening for celiac disease was evaluated at 15, 24, and 36 months and at 5, 8, and 10 years. Patients with positive serologic findings underwent intestinal biopsies. The primary outcome was the prevalence of celiac disease autoimmunity and of overt celiac disease among the children at 5 years of age.

Results: Of the 707 participants who remained in the trial at 36 months, 553 had a standard-risk or high-risk HLA genotype and completed the study. At 2 years of age, significantly higher proportions of children in group A than in group B had celiac disease autoimmunity (16% vs. 7%, P=0.002) and overt celiac disease (12% vs. 5%, P=0.01). At 5 years of age, the between-group differences were no longer significant for autoimmunity (21% in group A and 20% in group B, P=0.59) or overt disease (16% and 16%, P=0.78 by the log-rank test). At 10 years, the risk of celiac disease autoimmunity was far higher among children with high-risk HLA than among those with standard-risk HLA (38% vs. 19%, P=0.001), as was the risk of overt celiac disease (26% vs. 16%, P=0.05). Other variables, including breast-feeding, were not associated with the development of celiac disease.

Conclusions: Neither the delayed introduction of gluten nor breast-feeding modified the risk of celiac disease among at-risk infants, although the later introduction of gluten was associated with a delayed onset of disease. A high-risk HLA genotype was an important predictor of disease. (Funded by the Fondazione Celiachia of the Italian Society for Celiac Disease; CELIPREV ClinicalTrials.gov number, NCT00639444.).

Publication types

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

MeSH terms

  • Age Factors
  • Age of Onset
  • Autoantibodies / blood
  • Breast Feeding
  • Celiac Disease / diagnosis
  • Celiac Disease / genetics
  • Celiac Disease / prevention & control*
  • Child
  • Child, Preschool
  • Diet*
  • Dietary Proteins / administration & dosage*
  • Female
  • GTP-Binding Proteins / immunology
  • Genotype
  • Gliadin / immunology
  • Glutens* / administration & dosage
  • HLA Antigens / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Intestine, Small / pathology
  • Kaplan-Meier Estimate
  • Male
  • Prospective Studies
  • Risk
  • Transglutaminases / immunology

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00639444