title: Age at gluten introduction and risk of celiac disease.
abstract: OBJECTIVE
  The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children.
  
  
  METHODS
  TEDDY (The Environmental Determinants of Diabetes in the Young) is a prospective birth cohort study. Newborn infants (N = 6436) screened for high-risk HLA-genotypes for CD were followed up in Finland, Germany, Sweden, and the United States. Information about infant feeding was collected at clinical visits every third month. The first outcome was persistent positive for tissue transglutaminase autoantibodies (tTGA), the marker for CD. The second outcome was CD, defined as either a diagnosis based on intestinal biopsy results or on persistently high levels of tTGA.
  
  
  RESULTS
  Swedish children were introduced to gluten earlier (median: 21.7 weeks) compared with children from Finland (median: 26.1 weeks), Germany, and the United States (both median: 30.4 weeks) (P < .0001). During a median follow-up of 5.0 years (range: 1.7-8.8 years), 773 (12%) children developed tTGA and 307 (5%) developed CD. Swedish children were at increased risk for tTGA (hazard ratio: 1.74 [95% CI: 1.47-2.06]) and CD (hazard ratio: 1.76 [95% CI: 1.34-2.24]) compared with US children, respectively (P < .0001).Gluten introduction before 17 weeks or later than 26 weeks was not associated with increased risk for tTGA or CD, adjusted for country, HLA, gender, and family history of CD, neither in the overall analysis nor on a country-level comparison.
  
  
  CONCLUSIONS
  In TEDDY, the time to first introduction to gluten introduction was not an independent risk factor for developing CD.
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden; carin.andren_aronsson@med.lu.se.
authors.forename: Carin Andrén
authors.initials: CA
authors.lastname: Aronsson
authors.affiliation: Pediatrics Epidemiology Center, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida;
authors.forename: Hye-Seung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Digestive Health Institute, University of Colorado, Children's Hospital Colorado, Denver, Colorado;
authors.forename: Edwin
authors.initials: E
authors.lastname: Liu
authors.affiliation: Pediatrics Epidemiology Center, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida;
authors.forename: Ulla
authors.initials: U
authors.lastname: Uusitalo
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V., Neuherberg, Germany;
authors.forename: Sandra
authors.initials: S
authors.lastname: Hummel
authors.affiliation: Pediatrics Epidemiology Center, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida;
authors.forename: Jimin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V., Neuherberg, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, Colorado;
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia;
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
authors.affiliation: Department of Pediatrics, Turku University Hospital, Turku, Finland;
authors.forename: Olli
authors.initials: O
authors.lastname: Simell
authors.affiliation: Department of Physiology and Pediatrics, University of Turku, Turku, Finland;
authors.forename: Jorma
authors.initials: J
authors.lastname: Toppari
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V., Neuherberg, Germany;
authors.forename: Anette-G
authors.initials: AG
authors.lastname: Ziegler
authors.affiliation: Pediatrics Epidemiology Center, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida;
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Krischer
authors.affiliation: National Institutes for Health and Welfare, Nutrition Unit, Helsinki, Finland; School of Health Sciences, University of Tampere, Tampere, Finland; Research Center for Child Health, Tampere University and University Hospital and the Science Center of Pirkanmaa Hospital District, Tampere, Finland; and.
authors.forename: Suvi M
authors.initials: SM
authors.lastname: Virtanen
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, University of Colorado, Denver, Aurora, Colorado.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden;
authors.forename: Daniel
authors.initials: D
authors.lastname: Agardh
mesh_terms: D000367:Age Factors; D002446:Celiac Disease / Q000235:genetics* / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003431:Cross-Cultural Comparison; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005983:Glutens / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D008297:Male; D016016:Proportional Hazards Models; D012306:Risk; D014481:United States
chemical_list: D005983:Glutens
keywords: breastfeeding; celiac disease; gluten; infant feeding