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.
Highlights
Asthma is one of the most common chronic conditions among children [1]
Out of 222,247 children included in the study, 106,347 were born to mothers exposed to the margarine fortification policy with extra vitamin D during pregnancy; 115,900 were born to unexposed mothers
The Schoenfeld residuals indicated violation of the proportional hazards assumption with respect to exposure status, and when stratified by age at first diagnoses, we found that among the 0–3 years old, those exposed to extra vitamin D from fortification were less likely to have an inpatient asthma admission (HR 0.86, 95% CI: 0.75–0.98) compared to unexposed ones
Summary
Asthma is one of the most common chronic conditions among children [1]. Genetic factors and childhood exposure to environmental triggers, such as tobacco smoke, air pollution, viral infections or aeroallergens play a major role in the development of childhood asthma [3], it has been suggested that environmental exposures during gestation may be important [4]. Asthma is more prevalent among boys until puberty when a shift towards higher prevalence among girls and women is observed [5,6]. In children, this is thought to be due to sex differences in lung development and inflammatory profile [7]
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