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Original Investigation
August 13, 2019

Association of Gluten Intake During the First 5 Years of Life With Incidence of Celiac Disease Autoimmunity and Celiac Disease Among Children at Increased Risk

Author Affiliations
  • 1Department of Clinical Sciences, Lund University, Malmö, Sweden
  • 2Health Informatics Institute, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa
  • 3Dr von Hauner Children’s Hospital, Ludwig Maximilians University, Munich, Germany
  • 4University of Warmia and Mazuri, Olsztyn, Poland
  • 5Digestive Health Institute, University of Colorado Denver, Children’s Hospital Colorado, Denver
  • 6Tampere Centre for Child Health Research, University of Tampere, Tampere University Hospital, Tampere, Finland
  • 7School of Clinical Sciences, University of Bristol, Bristol, England
  • 8Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland
  • 9Department of Pediatrics, Turku University Hospital, Turku, Finland
  • 10Institute of Diabetes Research, Helmholtz Zentrum München, Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes eV, Neuherberg, Germany
  • 11Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, Georgia
  • 12Pacific Northwest Diabetes Research Institute, Seattle, Washington
  • 13Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora
  • 14National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland
  • 15National Institute for Health and Welfare, Department of Public Health Solutions, Helsinki, Finland
  • 16Faculty of Social Sciences/Health Sciences, University of Tampere, Tampere, Finland
  • 17Research Center for Child Health, Tampere University, University Hospital, Science Center of Pirkanmaa Hospital District, Tampere, Finland
  • 18Colorado School of Public Health, Department of Epidemiology, University of Colorado, Aurora
JAMA. 2019;322(6):514-523. doi:10.1001/jama.2019.10329
Key Points

Question  Is the amount of gluten intake during the first 5 years of life associated with the risk of celiac disease autoimmunity and celiac disease in at-risk children?

Findings  In this multinational prospective birth cohort consisting of 6605 genetically predisposed children, higher gluten intake was associated with a statistically significant increase in celiac disease autoimmunity (absolute risk difference, 6.1%) and celiac disease (absolute risk difference, 7.2%) for every gram increase of gluten intake per day.

Meaning  Increased intake of gluten during the first 5 years of life was an independent risk factor for celiac disease autoimmunity and celiac disease in genetically predisposed children.

Abstract

Importance  High gluten intake during childhood may confer risk of celiac disease.

Objectives  To investigate if the amount of gluten intake is associated with celiac disease autoimmunity and celiac disease in genetically at-risk children.

Design, Setting, and Participants  The participants in The Environmental Determinants of Diabetes in the Young (TEDDY), a prospective observational birth cohort study designed to identify environmental triggers of type 1 diabetes and celiac disease, were followed up at 6 clinical centers in Finland, Germany, Sweden, and the United States. Between 2004 and 2010, 8676 newborns carrying HLA antigen genotypes associated with type 1 diabetes and celiac disease were enrolled. Screening for celiac disease with tissue transglutaminase autoantibodies was performed annually in 6757 children from the age of 2 years. Data on gluten intake were available in 6605 children (98%) by September 30, 2017.

Exposures  Gluten intake was estimated from 3-day food records collected at ages 6, 9, and 12 months and biannually thereafter until the age of 5 years.

Main Outcomes and Measures  The primary outcome was celiac disease autoimmunity, defined as positive tissue transglutaminase autoantibodies found in 2 consecutive serum samples. The secondary outcome was celiac disease confirmed by intestinal biopsy or persistently high tissue transglutaminase autoantibody levels.

Results  Of the 6605 children (49% females; median follow-up: 9.0 years [interquartile range, 8.0-10.0 years]), 1216 (18%) developed celiac disease autoimmunity and 447 (7%) developed celiac disease. The incidence for both outcomes peaked at the age of 2 to 3 years. Daily gluten intake was associated with higher risk of celiac disease autoimmunity for every 1-g/d increase in gluten consumption (hazard ratio [HR], 1.30 [95% CI, 1.22-1.38]; absolute risk by the age of 3 years if the reference amount of gluten was consumed, 28.1%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 34.2%; absolute risk difference, 6.1% [95% CI, 4.5%-7.7%]). Daily gluten intake was associated with higher risk of celiac disease for every 1-g/d increase in gluten consumption (HR, 1.50 [95% CI, 1.35-1.66]; absolute risk by age of 3 years if the reference amount of gluten was consumed, 20.7%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 27.9%; absolute risk difference, 7.2% [95% CI, 6.1%-8.3%]).

Conclusions and Relevance  Higher gluten intake during the first 5 years of life was associated with increased risk of celiac disease autoimmunity and celiac disease among genetically predisposed children.

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