Placental contributions to disparities in offspring cardiovascular health across the life course

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PROJECT SUMMARY/ABSTRACT There are significant and persistent racial and socioeconomic disparities in cardiovascular disease (CVD) in the United States. Growing evidence indicates that the perinatal period is a critical window for intergenerational transmission of CVD disparities. Infants born preterm or small for gestational age are at greater risk of CVD morbidity and mortality in adulthood. Further, disparities in preterm birth and small for gestational age infant mirror those observed in CVD. As the organ at the maternal-fetal interface responsible for regulating fetal development, the placenta is the key to understanding intergenerational transmission of disparities. Consistent with this view, studies have reported that reduced placental size is associated with offspring CVD, though placental size is a crude measure of function. Techniques to improve assessment of placental function include histologic evaluation for vascular and inflammatory lesions and image analysis to evaluate vascular structure. Studies leveraging these robust placental measures have important scientific and clinical implications. Scientifically, they yield deeper mechanistic insights about the gestational origins of CVD risk, which can inform development of gestational interventions. Clinically, they have the potential to mitigate CVD disparities by improving risk stratification and informing treatment approaches. Accordingly, the goal of this proposal is to understand the placental mechanisms underlying racial and socioeconomic disparities in offspring cardiovascular health across the life course. Evaluating placental measures in relation to offspring cardiovascular health will be accomplished by initiating pediatric cardiovascular follow up in offspring from the Stress Pregnancy and Health study (SPAH; N=150). In addition, two complementary cohorts with routine placental data collection and longitudinal follow up will be leveraged: the Collaborative Perinatal Project (CPP; N=43,837) and the Avon Longitudinal Study of Parents and Children (ALSPAC; N=799). These cohorts will be used to address three aims. Aim 1: To determine whether placental dysfunction impacts CVD risk factor disparities in childhood by (a) evaluating placental lesions and vascular structure and (b) leveraging a sibling comparison design to control for parental and environmental confounding. Aim 2: To determine whether placental lesions are associated with disparities in cardiovascular structure, function, and CVD risk factors in adolescence and young adulthood. Aim 3: To determine whether placental lesions are associated with disparities in offspring premature CVD mortality in adulthood. As a perinatal epidemiologist, this award will help me extend my expertise to evaluating offspring cardiovascular outcomes. Through the process of conducting this research, I will obtain mentorship and training in leading longitudinal studies, comprehensive placental evaluation, and cardiovascular health across the life course. Collectively, this research and training will equip me with the expertise necessary to develop a unique research career investigating placental contributions to disparities in offspring cardiovascular health across the life course.