Project Details
Description
Congenital heart defects (CHD) are among the most frequent birth defects and remain an important cause of infant morbidity and mortality. The prevalence and severity of CHD place an enormous burden on the health care system, and thus strategies to prevent CHD and improve outcomes could benefit many children and save billions of dollars in resource utilization. A major barrier to the prevention of CHD is uncertainty regarding its etiology. Despite strong evidence for a genetic basis, a genetic etiology is identified only in 20-30% of isolated CHD cases. We hypothesize that the maternal-fetal environment and CHD are intricately linked via the placenta and that unique epigenetic signatures are detectable in the maternal circulation, the placenta and fetus that provide insight into the etiology of CHD and predict clinical outcomes. Emerging evidence links placental function to cardiac development, the socalled heart-placenta axis. For example, global deletion of p38𝛼-MAP kinase or PPAR-γ results in cardiac defects that are rescued by selective expression of these genes in the placenta. Furthermore, impeding blood flow in utero recapitulates hypoplastic left heart syndrome (HLHS) in animal models. As blood flow provided by the placental is the major determinant of early fetal cardiac output, early placental dysfunction might impact cardiac morphogenesis. We hypothesize that mediators of placental function, circulating placenta-derived miRNAs, placenta DNA methylation and the placental transcriptome, are differentially altered in CHD versus control pregnancies, contribute to the etiology of CHD and influence clinical outcomes. We propose a prospective cohortcontrol study design to determine the relationships between placental function, epigenetics, CHD etiology and 1-year outcomes in a high-risk subset of infants with CHD. We will focus on epigenetic modifications and pathophysiologic pathways relevant to the heart-placenta axis, leveraging our multidisciplin
Status | Finished |
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Effective start/end date | 5/1/19 → 6/30/21 |
Funding
- University of Utah (Agmt. 10045336-05 // Agmt. 10045336-05)
- American Heart Association (Agmt. 10045336-05 // Agmt. 10045336-05)
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