Longitudinal micronutrient exposure reveals country-specific associations with risk of celiac disease in genetically susceptible children: the prospective TEDDY cohort - UTU Research Portal

A1 Refereed original research article in a scientific journal

Longitudinal micronutrient exposure reveals country-specific associations with risk of celiac disease in genetically susceptible children: the prospective TEDDY cohort

Authors: Yang, Jimin; Mramba, Lazarus K.; Hård af Segerstad, Elin M.; Kurppa, Kalle; Uusitalo, Ulla; Aronsson, Carin Andrén; Rewers, Marian J.; McIndoe, Richard A.; Toppari, Jorma; Ziegler, Anette-G.; Hagopian, William A.; Akolkar, Beena; Krischer, Jeffrey P.; Norris, Jill M.; Virtanen, Suvi M.; Agardh, Daniel

Publication year: 2026

Journal: American Journal of Clinical Nutrition

Article number: 101276

Volume: 123

Issue: 5

ISSN: 0002-9165

eISSN: 1938-3207

DOI: https://doi.org/10.1016/j.ajcnut.2026.101276

Publication's open availability at the time of reporting: No Open Access

Publication channel's open availability : Partially Open Access publication channel

Web address : https://doi.org/10.1016/j.ajcnut.2026.101276

Abstract

Background

The role of nutrient intake in celiac disease pathogenesis is poorly understood.

Objectives

This study aims to examine whether longitudinal childhood intake of selected vitamins and minerals is associated with celiac disease autoimmunity (CDA, primary outcome) and celiac disease (secondary outcome) in genetically at-risk children.

Methods

A total of 6520 human leukocyte antigens-conferred at-risk children in the observational The Environmental Determinants of Diabetes in the Young (TEDDY) study were prospectively screened for tissue transglutaminase autoantibodies (tTGA) annually from ages 2 to 13 y. CDA was defined as persistent tTGA positivity in 2 samples ≥3 mo apart. Celiac disease was defined by biopsy-confirmed Marsh score ≥2 or mean tTGA ≥100 U/mL in 2 consecutive samples. Micronutrient intake was assessed via repeated 3-d food records, and adjusted hazard ratios (HRs) were estimated using time-dependent Cox proportional hazards and Bayesian joint models.

Results

Out of 6520 children, 1268 (19%) developed CDA and 479 (7.8%) were diagnosed with celiac disease. Results from both models suggested heterogeneity in associations by country as nutrients such as folate showed sporadic associations in the same or opposite direction across ages. Higher vitamin D intake (every 5 μg/1000 kcal) at multiple ages was associated with increased risk of CDA and celiac disease in Sweden, with the strongest at age 5 y for CDA [HR: 1.23, 95% confidence interval (CI): 1.11, 1.37; P < 0.001] and at age 4 y for celiac disease (HR: 1.20; 95% CI: 1.03, 1.40; P = 0.021). Higher iron intake (every 5 mg/1000 kcal) was also associated with increased risks of CDA and celiac disease in Sweden, with the highest observed up to age 5 y (HR: 1.70; 95% CI: 1.39, 2.08; P < 0.001 for CDA and HR:1.80; 95% CI: 1.37, 2.36; P < 0.001 for celiac disease).

Conclusions

Modest country-specific associations were found between childhood micronutrient intake with risk of CDA and celiac disease, potentially reflecting the influence from regional dietary practices, fortification policies, and host factors in disease pathogenesis.

Funding information in the publication:
The TEDDY Study is funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, U01 DK124166, U01 DK128847, and Contract No. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), Centers for Disease Control and Prevention (CDC), and Breakthrough T1D (formerly JDRF). This work is supported in part by the NIH/NCATS Clinical and Translational Science Awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR002535). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in the design, execution, or interpretation of the research. Breakthrough T1D (formerly JDRF)" to the funding resources.