Impact of Vitamin D and Asthma on Preeclampsia Development: A Sequential Evidence-Based Approach to Genomic Analysis

Abstract

The biologic evidence regarding the role for vitamin D in immunologic mechanisms and reproductive outcomes is strong. Epidemiologic studies have shown a high prevalence of vitamin D deficiency among pregnant women, especially among high-risk groups. Vitamin D has been also been linked to asthma attacks, another proposed risk factor for preeclampsia. Association of vitamin D and severe asthma has been studied in general population . Along with a clear genetic basis in atopic asthma, environmental factors, including early neonatal nutrition, may have an important influence on asthma development. Vitamin D may be an important environmental factor influencing asthma outcomes. A recent meta-analysis investigated the adverse perinatal outcomes in women with asthma and concluded that as much as a 50% increase risk of PE development in asthmatic pregnant women. Interestingly, in preeclampsia, epidemiologic studies have implicated alterations in vitamin D metabolism and low vitamin D status during pregnancy.

The objective of this dissertation is to investigate the potential confounding/modulating effect of vitamin D in the association of asthma and preeclampsia as well as its role in gene expressions in early pregnancy of preeclamptic women. To achieve this goal, a sequential approach from abstracting available literature evidences, to epidemiologic and genomic analyses in proposed. Accordingly, in the introductory chapter one of this dissertation, we provide an evidence-based literature review on the role of vitamin D in asthma development or its severity, fetal development and healthy pregnancy as well as immunomodulation and conclude that vitamin D could have modulating effect on asthma and play important role in human development. In chapter two, we investigate the association between maternal asthma and serum level of vitamin D in early pregnancy with the risk of preeclampsia development, using data on the outcomes of pregnancy from the Vitamin D Antenatal Randomized Trial. In chapter three, we explore the influence of vitamin D on the expression of genes, potentially involved in the development of preeclampsia. Finally, in chapter four, the importance of our findings in the three previous chapters will be reviewed and the future perspective that this evidence based approach investigation proposes will be discussed.