Assessing Health Consequences of Vitamin D Fortification Utilizing a Societal Experiment Design: Methodological Lessons Learned from the D-Tect Project
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Prenatal Vitamin D and the Risk of Type 1 Diabetes
3.2. Prenatal Vitamin D and Birth Weight and Childhood Obesity
3.3. Prenatal Vitamin D and the Risk of Fractures in Late Childhood
3.4. Prenatal Vitamin D and the Risk of Gestational Diabetes, Pre-Eclampsia, Childhood Asthma, Adult Celiac Disease, and Inflammatory Bowel Disease
3.5. Other Fortification Experiment-Based Studies in the D-Tect Project
4. Discussion
4.1. Historical Information
4.2. Methodological Issues on Data: Sources, Outcomes, and Covariates
4.3. Methodological Issues on Statistical Approaches
4.4. Lessons Concerning Studying Exposure to Vitamin D
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Outcomes | Aim | Participants | Data Source | Statistical Methods |
---|---|---|---|---|
Type 1 diabetes (T1D) [10,11] | To examine whether gestational and early infancy exposure to low-dose vitamin D from a mandatory margarine fortification program in Denmark influenced the risk of developing T1D before the age of 15 years. | Children aged 0–14 years | Civil registration numbers linked to the the Danish Childhood Diabetes Registry | Cox regression models |
To examine whether gestational and early infancy exposure to margarine fortification was associated with seasonality of birth in Danish T1D patients. | Children aged 0–14 years | Civil registration numbers linked to the the Danish Childhood Diabetes Registry. Meteorological data of monthly gestational sunshine hours. | Cox regression models | |
Birthweight and body size [12,13,14,15] | To study the impact of the Danish vitamin D fortification programs on birthweight. | Newborn | Copenhagen School Health Record Register | Linear and logistic regression models |
To investigate whether prenatal exposure to vitamin-D fortification of margarine and low-fat milk was also associated with body size at 7 years of age. | Children aged 7 years | Copenhagen School Health Record Register | Linear and logistic regression models | |
Fractures [16] | To examine the risk of fractures among adolescents from proximate birth cohorts born around the date of the termination of a mandatory national vitamin D fortification program. | Children aged 10–18 years | Civil registration numbers linked to the Danish National Patient Registry | Multiplicative Poisson models (age, period, cohort) |
Gestational diabetes mellitus (GDM) [17] | To examine whether exposure during fetal life to extra vitamin D from food fortification was associated with a reduction in the risk of subsequently developing GDM and to examine whether the effect of the vitamin D from fortification differed by women’s season of birth. | Nulliparous women aged 20–28 years giving birth after gestational week 22 during the period from 2004 to 2016 | Civil registration numbers linked to the Danish National Patient Registry and the Danish Medical Birth Register | Logistic regression models |
Pre-eclampsia [18] | To examine whether fetal exposure to a small dosage of extra vitamin D from food fortification was associated with a decrease in the risk of pre-eclampsia later in life. | Nulliparous women aged 14–28 years giving birth after gestational week 22 | Civil registration numbers linked to the Danish National Patient Registry | Logistic regression model |
Asthma [20] | To examine whether children born to women exposed to the margarine fortification policy with a small dose of extra vitamin D during pregnancy had a reduced risk of developing asthma until age 9, compared to children born to unexposed women. | Children aged 0–9 years | Civil registration numbers linked to the Danish National Patient Registry | Cox regression models |
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. | Individuals up to age 30 | Civil registration numbers linked to the Danish National Patient Registry | Logistic regression models |
Inflammatory bowel disease (IBD) [22] | To examine whether season of birth or prenatal exposure to extra vitamin D from food fortification were associated with developing IBD later in life. | Individuals up to age 30 | Civil registration numbers linked to the Danish National Patient Registry | Logistic regression models |
Type 2 diabetes mellitus (T2DM) [24] | To examine whether exposure during fetal life to extra vitamin A from food fortification was related to subsequent risk of developing T2DM in adulthood (before age 49). | Individuals aged between 36 to 49 years | Civil registration numbers linked to the Danish National Patient Registry and Danish National Diabetes Register | Logistic regression models |
Outcomes | Aim | Participants | Data Source | Statistical Methods |
---|---|---|---|---|
Pre-eclampsia [19] | To examine whether exposure to extra vitamin D from food fortification was associated with a decrease in the risk of preeclampsia | All nulliparous women giving birth after gestational week 22 in the period 1 June 1983 to the 31 August 1988 | Civil registration numbers linked to the Danish National Patient Registry | Logistic regression models |
Live births in women diagnosed with infertility [23] | To examine the association between extra vitamin D from a mandatory margarine fortification program and chance of live birth among infertile women | All women diagnosed with primary infertility from 1 September 1986, to 31 August 1991. Any live birth for each woman in the cohort within a follow-up period of 12 months after the initial infertility diagnosis date. | Civil registration numbers linked to the Danish National Patient Registry, the Danish Medical Birth Register, the Danish Infertility Cohort, and the Danish In Vitro Fertilization Registry | Logistic regression models |
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Händel, M.N.; Jacobsen, R.; Thorsteinsdottir, F.; Keller, A.C.; Stougaard, M.; Jensen, C.B.; Moos, C.; Duus, K.S.; Jensen, A.; Schiøler Kesmodel, U.; et al. Assessing Health Consequences of Vitamin D Fortification Utilizing a Societal Experiment Design: Methodological Lessons Learned from the D-Tect Project. Int. J. Environ. Res. Public Health 2021, 18, 8136. https://doi.org/10.3390/ijerph18158136
Händel MN, Jacobsen R, Thorsteinsdottir F, Keller AC, Stougaard M, Jensen CB, Moos C, Duus KS, Jensen A, Schiøler Kesmodel U, et al. Assessing Health Consequences of Vitamin D Fortification Utilizing a Societal Experiment Design: Methodological Lessons Learned from the D-Tect Project. International Journal of Environmental Research and Public Health. 2021; 18(15):8136. https://doi.org/10.3390/ijerph18158136
Chicago/Turabian StyleHändel, Mina Nicole, Ramune Jacobsen, Fanney Thorsteinsdottir, Amélie Cléo Keller, Maria Stougaard, Camilla Bjørn Jensen, Caroline Moos, Katrine Sidenius Duus, Allan Jensen, Ulrik Schiøler Kesmodel, and et al. 2021. "Assessing Health Consequences of Vitamin D Fortification Utilizing a Societal Experiment Design: Methodological Lessons Learned from the D-Tect Project" International Journal of Environmental Research and Public Health 18, no. 15: 8136. https://doi.org/10.3390/ijerph18158136