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.