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Gluten Intake and Risk of Celiac Disease

Long-Term Follow-up of an At-Risk Birth Cohort

Mårild, Karl MD, PhD1,2; Dong, Fran MS3; Lund-Blix, Nicolai A. PhD1,3,4; Seifert, Jennifer MPH5; Barón, Anna E. PhD6; Waugh, Kathleen C. MS3; Taki, Iman BS3; Størdal, Ketil MD, PhD1,7; Tapia, German PhD1; Stene, Lars C. PhD1; Johnson, Randi K. MPH5; Liu, Edwin MD3; Rewers, Marian J. MD, PhD3; Norris, Jill M. MPH, PhD5

American Journal of Gastroenterology: August 2019 - Volume 114 - Issue 8 - p 1307–1314
doi: 10.14309/ajg.0000000000000255

OBJECTIVES: To determine the association between the amount of gluten intake in childhood and later celiac disease (CD), for which data are currently scarce.

METHODS: The prospective Diabetes Autoimmunity Study in the Young cohort includes 1875 at-risk children with annual estimates of gluten intake (grams/d) from age 1 year. From 1993 through January 2017, 161 children, using repeated tissue transglutaminase (tTGA) screening, were identified with CD autoimmunity (CDA) and persistent tTGA positivity; of these children, 85 fulfilled CD criteria of biopsy-verified histopathology or persistently high tTGA levels. Cox regression, modeling gluten intake between ages 1 and 2 years (i.e., in 1-year-olds), and joint modeling of cumulative gluten intake throughout childhood were used to estimate hazard ratios adjusted for confounders (aHR).

RESULTS: Children in the highest third of gluten intake between the ages of 1 and 2 years had a 2-fold greater hazard of CDA (aHR 2.17; 95% confidence interval [CI], 1.22–3.88; P value = 0.01) and CD (aHR 1.96; 95% CI, 0.90–4.24; P value = 0.09) than those in the lowest third. The risk of developing CDA increased by 5% per daily gram increase in gluten intake (aHR 1.05; 95% CI, 1.00–1.09; P value = 0.04) in 1-year-olds. The association between gluten intake in 1-year-olds and later CDA or CD did not differ by the child's human leukocyte antigen genotype. The incidence of CD increased with increased cumulative gluten intake throughout childhood (e.g., aHR 1.15 per SD increase in cumulative gluten intake at age 6; 95% CI, 1.00–1.32; P value = 0.04).

DISCUSSION: Gluten intake in 1-year-olds is associated with the future onset of CDA and CD in children at risk for the disease.

1Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway;

2Department of Pediatrics, Queen Silvia Children's Hospital, Gothenburg, Sweden;

3Barbara Davis Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA;

4Department of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway;

5Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA;

6Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA;

7Department of Pediatrics, Østfold Hospital Trust, Grålum, Norway.

Correspondence: Karl Mårild, MD, PhD. E-mail:

SUPPLEMENTARY MATERIAL accompanies this paper at

Received November 23, 2018

Accepted March 26, 2019

Online date: May 9, 2019

© The American College of Gastroenterology 2019. All Rights Reserved.
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