Exposure to Vitamin D Fortification Policy in Prenatal Life and the Risk of Childhood Asthma: Results from the D-Tect Study

Abstract

Prenatal vitamin D insufficiency may be associated with an increased risk of developing childhood asthma. Results from epidemiological studies are conflicting and limited by short follow-up and small sample sizes. The objective of this study was to examine if 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 years, compared to children born to unexposed women. The termination of a Danish mandatory vitamin D fortification policy constituted the basis for the study design. We compared the risk of inpatient asthma diagnoses in all Danish children born two years before (n = 106,347, exposed) and two years after (n = 115,900, unexposed) the termination of the policy. The children were followed in the register from 0–9 years of age. Data were analyzed using Cox proportional hazards regression. The Hazard Ratio for the first inpatient asthma admission among exposed versus unexposed children was 0.96 (95%CI: 0.90–1.04). When stratifying by sex and age, 0–3 years old boys exposed to vitamin D fortification showed a lower asthma risk compared to unexposed boys (HR 0.78, 95%CI: 0.67–0.92). Prenatal exposure to margarine fortification policy with extra vitamin D did not affect the overall risk of developing asthma among children aged 0–9 years but seemed to reduce the risk among 0–3 years old boys. Taking aside study design limitations, this could be explained by different sensitivity to vitamin D from different sex-related asthma phenotypes in children with early onset, and sex differences in lung development or immune responses.

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

“…The differences in monthly sunshine hours per year between 1983-1988 were not significant [47,48]. The consumption of margarine during this period was remarkably stable [49]. As a result of the above, the assumption has been made that sources of vitamin D were not different between the two cohorts.…”

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

“…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].…”

“…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.…”

“…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.…”

“…These women were identified using information from the Danish Medical Birth Register [31], where information on covariates (e.g., mother's smoking during pregnancy and pre-pregnancy BMI, offspring's gestational age at birth and sex) was also obtained. For asthma outcomes, the focus was on the time of the first inpatient asthma diagnosis admission at age 0-9 years [20]. For celiac disease and IBD, the focus was on the first admission with a diagnosis at age 0-30 years [21,22. Due to the design, where individuals from entire adjacent birth cohorts were examined, unmeasured covariates were considered to be equally distributed between adjacent exposed and unexposed birth cohorts.…”