PROJECT SUMMARY The escalating health and economic burden of non-communicable disease (NCD) represents a global health challenge that disproportionally affects women and children in low- and middle-income countries (LMICs). Adverse environmental conditions in early life such as impaired fetal growth or birth to a preeclamptic (PreE) mother increase susceptibility to NCD across the lifespan. In Bolivia, maternal and infant mortality and morbidity rates are the third highest in the Western Hemisphere due, in part, to the fact that two-thirds of its population resides at high altitude (? 2500 m) where the incidence of PreE and fetal growth restriction is three- fold greater relative to low altitude. Bolivia also suffers from an increasing prevalence of cardiovascular disease (CVD) with congenital cardiac defects, neonatal pulmonary hypertension, adult-onset pulmonary vascular disease, right heart failure and polycythemia being more common at high than at low altitude. Our objective is to lay the foundation for sustainable research programs designed to identify mechanistic links between antenatal exposures that are of particular relevance at high-altitudes in Bolivia (e.g., PreE, intrauterine hypoxia) and the development NCDs. Towards this goal, we will first conduct a series of targeted workshops in La Paz, the administrative capital and home to the major public medical university in Bolivia, for engaging leading Bolivian practitioners, medical researchers and health-policy makers to update and standardize diagnostic criteria and treatment strategies for hypertensive pregnancy complications because accurate diagnosis of these conditions is a critical starting point for prospective studies of perinatal exposures and NCD risk, and use of recently updated guidelines are not yet standard practice in Bolivia. Concurrently, we will leverage resources provided by the Global Pregnancy Collaboration (CoLab) to establish a centralized, online perinatal database (The COLLECT Global Collaboration Database) and an accompanying biorepository in La Paz, Bolivia that will be tailored for the collection of prospective data using mobile-health technologies. Based on extensive evidence that epigenomic mechanisms play a pivotal role for the effect of environmental exposures in early life to increase NCD risk, and our preliminary data suggesting that PreE modifies epigenetic and gene expression patterns of genes important for cardiopulmonary vascular development, pulmonary hypertension and CVD, we will then use the perinatal database and biorepository to conduct an exploratory study to determine the role of epigenetic processes for the link between PreE and development of pulmonary vascular dysfunction during infancy. Together, our proposed studies will a) enable improvements in clinical practice and health policy likely to reduce the frequency of cardiopulmonary diseases later in life for both mother and child in Bolivia, b) build research capacity for enabling LMIC investigators to conduct further studies on the mechanisms linking early- life exposures and NCDs, and, in the long-term, c) reduce NCD-related morbidity and mortality.

R21TW010797

2017-09-15

2020-06-30