Epigenetic biomarkers of preeclampsia risk among mothers with chronic hypertension

ABSTRACT Preeclampsia (preE) is a potentially fatal complication of pregnancy that affects 2-8% of pregnancies worldwide. Preeclampsia is characterized by hypertension and proteinuria. Interestingly, the incidence of preE demonstrates a seasonal pattern, whereby summer months conception (in the Northern Hemisphere) is

associated with the highest rates of preE. In the Northern Hemisphere, summer months are associated with hotter temperatures compared to the winter months. High ambient temperatures are associated with several negative health outcomes. For example, high ambient temperatures have been linked to increased incidence of

acute cardiovascular disease and worsening chronic cardiovascular disease. Similarly, kidney function is significantly negatively impacted by high ambient temperatures. Given the central role of cardiovascular and renal systems in the pathophysiology of preE, the association between elevated ambient temperatures and

adverse maternal-fetal outcomes assumes particular significance in the context of preE. Advanced maternal age is also a risk factor for preE. Like chronological age, there is evidence supporting an association between epigenetic age acceleration and preE. Exhibition of epigenetic age acceleration has been strongly correlated

with age-related diseases but has been scarcely studied in preE. The goals of this project are to: 1) Test the association between the number of high ambient heat days during the first trimester with preE status during the current pregnancy and identify the critical threshold at which ambient heat during the first trimester

impacts preE and 2) Test the association between epigenetic age acceleration and preE status during the current pregnancy; and among participants diagnosed with preE during the current pregnancy, explore whether high ambient heat days modify the association between epigenetic age acceleration and preE. The

findings from this study will provide epidemiologic and environmental evidence about the additional risk heat may play for preE among individuals already experiencing chronic hypertension. Additionally, this project will add to our understanding of the relationship between preE and epigenetic age acceleration.