title: Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease.
abstract: BACKGROUND
  While gluten ingestion is responsible for the signs and symptoms of celiac disease, it is not known what factors are associated with initial appearance of the disease.
  
  
  OBJECTIVE
  To examine whether the timing of gluten exposure in the infant diet was associated with the development of celiac disease autoimmunity (CDA).
  
  
  METHODS
  Prospective observational study conducted in Denver, Colo, from 1994-2004 of 1560 children at increased risk for celiac disease or type 1 diabetes, as defined by possession of either HLA-DR3 or DR4 alleles, or having a first-degree relative with type 1 diabetes. The mean follow-up was 4.8 years.
  
  
  METHODS
  Risk of CDA defined as being positive for tissue transglutaminase (tTG) autoantibody on 2 or more consecutive visits or being positive for tTG once and having a positive small bowel biopsy for celiac disease, by timing of introduction of gluten-containing foods into the diet.
  
  
  RESULTS
  Fifty-one children developed CDA. Findings adjusted for HLA-DR3 status indicated that children exposed to foods containing wheat, barley, or rye (gluten-containing foods) in the first 3 months of life (3 [6%] CDA positive vs 40 [3%] CDA negative) had a 5-fold increased risk of CDA compared with children exposed to gluten-containing foods at 4 to 6 months (12 [23%] CDA positive vs 574 [38%] CDA negative) (hazard ratio [HR], 5.17; 95% confidence interval [CI], 1.44-18.57). Children not exposed to gluten until the seventh month or later (36 [71%] CDA positive vs 895 [59%] CDA negative) had a marginally increased risk of CDA compared with those exposed at 4 to 6 months (HR, 1.87; 95% CI, 0.97-3.60). After restricting our case group to only the 25 CDA-positive children who had biopsy-diagnosed celiac disease, initial exposure to wheat, barley, or rye in the first 3 months (3 [12%] CDA positive vs 40 [3%] CDA negative) or in the seventh month or later (19 [76%] CDA positive vs 912 [59%] CDA negative) significantly increased risk of CDA compared with exposure at 4 to 6 months (3 [12%] CDA positive vs 583 [38%] CDA negative) (HR, 22.97; 95% CI, 4.55-115.93; P = .001; and HR, 3.98; 95% CI, 1.18-13.46; P = .04, respectively).
  
  
  CONCLUSIONS
  Timing of introduction of gluten into the infant diet is associated with the appearance of CDA in children at increased risk for the disease.
authors.affiliation: Department of Preventive Medicine and Biometrics, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262, USA. jill.norris@uchsc.edu
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
authors.forename: Katherine
authors.initials: K
authors.lastname: Barriga
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Hoffenberg
authors.forename: Iman
authors.initials: I
authors.lastname: Taki
authors.forename: Dongmei
authors.initials: D
authors.lastname: Miao
authors.forename: Joel E
authors.initials: JE
authors.lastname: Haas
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Emery
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Sokol
authors.forename: Henry A
authors.initials: HA
authors.lastname: Erlich
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
mesh_terms: D001323:Autoantibodies; D015551:Autoimmunity; D001706:Biopsy; D002446:Celiac Disease / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology*; D002675:Child, Preschool; D004032:Diet; D002523:Edible Grain; D005983:Glutens / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D007421:Intestine, Small / Q000473:pathology; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D011503:Transglutaminases / Q000276:immunology
chemical_list: D001323:Autoantibodies; D005983:Glutens; D011503:Transglutaminases