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

AbstractBackgroundThe role of nutrient intake in celiac disease pathogenesis is poorly understood.ObjectivesThis 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.MethodsA 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.ResultsOut 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).ConclusionsModest 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.