Exposure to the Danish Mandatory Vitamin D Fortification Policy in Prenatal Life and the Risk of Developing Coeliac Disease—The Importance of Season: A Semi Ecological Study

Moos, Caroline; Duus, Katrine Sidenius; Frederiksen, Peder; Heitmann, Berit Lilienthal; Andersen, Vibeke

doi:10.3390/nu12051243

Cited by 5 publications

(7 citation statements)

References 49 publications

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“…The most promising promoters so far are gastrointestinal infections ( 12 , 13 ), high gluten intake ( 14 ), or both ( 15 ). For reasons yet unknown, children born during the spring and summer months are at the highest disease risk ( 16 – 20 ). This has led to the hypothesis that vitamin D deficiency in early life may predispose to celiac disease due to seasonal differences in UVB exposure and subsequent 25(OH)D concentrations or via dysregulation of the immune response leading to an abnormal intestinal mucosa with increasing permeability ( 21 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…The primary outcomes were type 1 diabetes [10,11], birth weight and childhood obesity [12][13][14][15], and childhood fractures [16]. Secondary outcomes were gestational diabetes [17], pre-eclampsia [18,19], childhood asthma [20], adult celiac disease [21], inflammatory bowel disease [22], chance of live birth among women with fertility problems [23], and type 2 diabetes mellitus [24].…”

Section: Resultsmentioning

confidence: 99%

“…A decreased risk for asthma was shown in boys under 3 years of age exposed to the fortification, compared to boys of the same age not exposed to fortification (HR 0.78, 95% CI 0.67, 0.92) with no modification effect by month of birth [20]. ORs for developing celiac disease were similar in exposed and unexposed cohorts, with no significant modification effect by season of birth [21]. Lower odds of IBD were found for indi- For gestational diabetes and pre-eclampsia outcomes, the focus was on the first diagnosis of the relevant outcomes in women from the selected cohorts, who gave birth for the first time at age 14-27 years for pre-eclampsia [18] or at age 20-27 years for gestational diabetes [17].…”

Section: Figurementioning

confidence: 87%

“…Celiac disease (CD) [21] To examine whether season of birth or prenatal exposure to extra vitamin D from food fortification were associated with developing CD later in life.…”

Section: Cox Regression Modelsmentioning

confidence: 99%

“…Another important issue was the high validity of fracture diagnoses codes from the Danish National Patient Register, due to the low risk of error when diagnosing fractures by radiology in the hospital setting. Studies analyzing the effect of gestational exposure to vitamin D fortified margarine on the risk of gestational diabetes [17], pre-eclampsia [18], childhood asthma [20], adult celiac disease [21], and inflammatory bowel disease (IBD) [22] later in life were subsequently published. The termination of the Danish fortification program in June 1985 constituted the basis of the study designs in these studies.…”

Section: Prenatal Vitamin D and The Risk Of Fractures In Late Childhoodmentioning

confidence: 99%

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Assessing Health Consequences of Vitamin D Fortification Utilizing a Societal Experiment Design: Methodological Lessons Learned from the D-Tect Project

Händel

Jacobsen

Thorsteinsdottir

et al. 2021

IJERPH

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By utilizing historical changes in Danish legislation related to mandatory vitamin D fortification of margarine, which was implemented in the mid 1930s and abruptly abandoned in June 1985, the studies in the D-tect project investigated the effects of vitamin D on health outcomes in individuals, who during gestation were exposed or unexposed to extra vitamin D from fortified margarine. This paper reviews and narratively summarizes the analytic approaches alongside the results of the societal fortification experiment studies from the D-tect project and addresses the challenges in designing societal experiment studies and evaluating their results. The latter are discussed as lessons learned that may be useful for designers of similar studies, expected to be extensively utilized while researching the health consequences of the COVID-19 pandemic by comparing individuals born before and after the epidemic. In the D-tect project, 16 articles based on the societal fortification experiment were published analyzing 10 different outcomes and using different statistical approaches. Lessons learned included the detail of the analysis of the historical information on the exposure, availability and validity of the outcome data, variety of analytical approaches, and specifics concerning vitamin D effect evaluation, such as consideration of the influence of sunshine or season. In conclusion, the D-tect project clearly demonstrated the cost-effectiveness and research potential of natural- or societal-experiment-based studies.

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Relevance of environmental cofactors

Francavilla,

Dargenio,

Castellaneta

et al. 2024

Pediatric and Adult Celiac Disease

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Exposure to the Danish Mandatory Vitamin D Fortification Policy in Prenatal Life and the Risk of Developing Coeliac Disease—The Importance of Season: A Semi Ecological Study

Cited by 5 publications

References 49 publications

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

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

Assessing Health Consequences of Vitamin D Fortification Utilizing a Societal Experiment Design: Methodological Lessons Learned from the D-Tect Project

Relevance of environmental cofactors

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