25(OH)D Levels in Infancy Is Associated With Celiac Disease Autoimmunity in At-Risk Children: A Case–Control Study

Carin Andrén Aronsson, Xiang Liu, Jill M. Norris, Ulla Uusitalo, Martha D. Butterworth, Sibylle Koletzko, Suvi M. Virtanen, Iris Erlund, Kalle Kurppa, William A. Hagopian, Marian J. Rewers, Jin Xiong She, Jorma Toppari, Anette G. Ziegler, Beena Akolkar, Jeffrey P. Krischer, Daniel Agardh, on behalf of the TEDDY Study Group

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Objectives: An observed variation in the risk of celiac disease, according to the season of birth, suggests that vitamin D may affect the development of the disease. The aim of this study was to investigate if vitamin D concentration is associated with the risk of celiac disease autoimmunity (CDA) in genetically at-risk children. Study Design: Children prospectively followed in the multinational The Environmental Determinants of Diabetes in the Young study, conducted at six centers in Europe and the US, were selected for a 1-to-3 nested case–control study. In total, 281 case–control sets were identified. CDA was defined as positivity for tissue transglutaminase autoantibodies (tTGA) on two or more consecutive visits. Vitamin D was measured as 25-hydroxyvitamin D [25(OH)D] concentrations in all plasma samples prior to, and including, the first tTGA positive visit. Conditional logistic regression was used to examine the association between 25(OH)D and risk of CDA. Results: No significant association was seen between 25(OH)D concentrations (per 5 nmol/L increase) and risk for CDA development during early infancy (odds ratio [OR] 0.99, 95% confidence interval [CI] 0.95–1.04) or childhood (OR 1.02, 95% CI 0.97–1.07). When categorizing 25(OH)D concentrations, there was an increased risk of CDA with 25(OH)D concentrations <30 nmol/L (OR 2.23, 95% CI 1.29, 3.84) and >75 nmol/L (OR 2.10, 95% CI 1.28–3.44) in early infancy, as compared with 50–75 nmol/L. Conclusion: This study indicates that 25(OH)D concentrations <30 nmol/L and >75 nmol/L during early infancy were associated with an increased risk of developing CDA in genetically at-risk children. The non-linear relationship raises the need for more studies on the possible role of 25(OH)D in the relation to celiac disease onset.

Original languageEnglish
Article number720041
JournalFrontiers in Nutrition
Publication statusPublished - 11 Aug 2021
Publication typeA1 Journal article-refereed


  • celiac disease
  • celiac disease autoimmunity
  • children
  • infants
  • vitamin D

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Food Science
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics


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