Influence of placental impairments and maternal-fetal environment on neurodevelopmental outcomes in Congenital Heart Disease

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ABSTRACT Congenital heart disease (CHD) is the most common birth defect, affecting around 40,000 infants each year. Due to advances in diagnosis and surgical techniques, for the first time, there are more adults living with CHD than children in the US. Particularly, CHD survivors are at varied risk for neurodevelopmental and neurocognitive delays. There is a pressing need to understand the various risk factors driving neurodevelopmental outcome in this population. During gestation, the placenta develops concomitantly with the heart and is critical to healthy development of the fetus. Recent evidence has shown that there is increased incidence of placental abnormalities in fetuses with CHD. Magnetic resonance imaging (MRI) is a safe, non-ionizing modality and provides a unique window of opportunity to non-invasively study the fetal environment, in-utero. This proposal seeks to elucidate the role of placental impairments, measured using MRI, in determining fetal and postnatal neurodevelopmental outcomes in CHD. Findings from this proposal will clarify how interactions between cardiac physiology, impaired placenta and other maternal-fetal risks drive heterogeneity of outcomes in CHD. This proposal is also designed to provide important scientific training and career development opportunities to allow Dr. Rajagopalan to advance to an independent career in using non-invasive, imaging-based biomarkers to enhance diagnosis of prenatal disorders and facilitate fetal therapy and intervention with a goal of improving neurodevelopmental outcomes. Dr. Rajagopalan’s work, thus far, has focused on developing novel methods – both fetal MRI techniques and computational techniques to answer both mechanistic and clinically relevant questions around birth anomalies. This K01 grant will facilitate Dr. Rajagopalan’s transition to an independent research career by providing her the necessary skills in: (1) cardiac physiology and developmental biology; (2) advanced MRI acquisition and multi-site study design; and (3) computational modeling that will allow me to become an independent scientist focused on advancing our understanding of, and ultimately the diagnosis and management of neurodevelopmental outcomes in CHD. In order to achieve these training goals, Dr. Rajagopalan has put together a training plan that comprises of didactic training and hands-on practica in developmental biology, advanced MR acquisition and processing, and clinical, pediatric cardiology. She is supported by her mentors: Dr. J. Wood M.D., an expert in in modeling hemodynamics in cardiac abnormalities using non-invasive MRI; Dr. A. Panigrahy M.D., with expertise in early neuroimaging and cardiac-neurodevelopmental outcomes. Together with the research proposal, the training plan will lay the foundation for Dr. Rajagopalan’s independent career in improving long-term neurodevelopmental outcomes in CHD survivors.