Carin Andrén Aronsson1, Hye-Seung Lee2, Edwin Liu3, Ulla Uusitalo2, Sandra Hummel4, Jimin Yang2, Michael Hummel4, Marian Rewers5, Jin-Xiong She6, Olli Simell7, Jorma Toppari8, Anette-G Ziegler4, Jeffrey Krischer2, Suvi M Virtanen9, Jill M Norris10, Daniel Agardh11. 1. Department of Clinical Sciences, Lund University, Malmö, Sweden; carin.andren_aronsson@med.lu.se. 2. Pediatrics Epidemiology Center, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida; 3. Digestive Health Institute, University of Colorado, Children's Hospital Colorado, Denver, Colorado; 4. Institute of Diabetes Research, Helmholtz Zentrum München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V., Neuherberg, Germany; 5. Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, Colorado; 6. Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; 7. Department of Pediatrics, Turku University Hospital, Turku, Finland; 8. Department of Physiology and Pediatrics, University of Turku, Turku, Finland; 9. 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. 10. Department of Epidemiology, Colorado School of Public Health, University of Colorado, Denver, Aurora, Colorado. 11. Department of Clinical Sciences, Lund University, Malmö, Sweden;
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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.
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