Preeclampsia Clinical Trials

The goal of this prospective observational cohort study of pregnant people at-risk of preeclampsia receiving aspirin as part of clinical care or a planned randomized controlled trial of 81mg vs. 162mg of aspirin is to generate proteomic data to show a distinct maternal and fetal Extracellular Vesicle (EV) proteome profile with aspirin treatment, and develop and validate a multi-marker panel for the monitoring of placental function in people at-risk of Preeclampsia and in response to aspirin treatment. The primary research question is: 1. Does the maternal and fetal Positive for Placental Alkaline Phosphatase (PLAP+) Extracellular Vesicle (EV) proteome profile in the 2nd and 3rd trimester of pregnancy differ between people who receive aspirin and develop (or not) preeclampsia? Participants will be asked to give blood samples up to four times during and at the end of their pregnancy. Read Less

The goal of this study is to assess the effect of an electronic health record (EHR) clinical decision support tool, also known as a best practice alert (BPA), on healthcare provider recommendations for low dose aspirin use in a high-risk pregnant patient population. The investigators hypothesize that the implementation of the EHR BPA tool will increase the healthcare provider's recommendation for low dose aspirin compared to current standard care. Read Less

Aspirin is recommended in high risk patients to reduce the risk of preeclampsia and preterm birth, which are leading causes of both maternal and neonatal morbidity and mortality, but up to 20% will have these adverse outcomes despite therapy. Gaps in knowledge regarding pregnancy specific aspirin pharmacology and the relationship of aspirin response and pregnancy outcome, along with a lack of consensus on aspirin dosing has limited the effective use of this intervention. The investigators aim to apply principles of clinical pharmacology to determine how to optimally utilize this low cost medication to improve maternal/child health outcomes. This is a Phase I/II randomized controlled trial of high risk pregnancies recommended aspirin; participants will be randomized to take aspirin either 162mg once daily, or 81mg twice a day. Outcomes evaluated will include the difference in aspirin response between these two dosing regimens, the individual factors that impact aspirin pharmacology in pregnancy, and evaluate markers or aspirin response that may be associated with pregnancy outcome. Read Less

Although extensively studied, the cause of preeclampsia remains uncertain other than it is thought that the placenta plays a critical role in the development of preeclampsia. Recent data revealed that exosomes released from the placenta could cause preeclampsia by transporting specific cargo responsible for the pathophysiological changes associated with the systemic disease. By isolating these exosomes from maternal blood and placental tissue in patients diagnosed with preeclampsia and studying their biochemical, cellular and molecular mechanism in an animal model, the investigators hope to elucidate the critical role that exosomal cargo plays in the development of preeclampsia and cardiovascular remodeling. This will be accomplished by obtaining patient samples from volunteers delivering at the Women and Infants Center and taking the samples to the lab for quantification, characterization, and identification of key functional roles through in/ex vivo, in vitro, and profiling studies. The investigators believe this work will be valuable as hope exists to define the functional role exosomes play in the development of preeclampsia that leads to cardiovascular remodeling. Data from this study will shed more light on the functional role of exosomal cargo in normal and pathological pregnancies and point towards novel therapeutic intervention strategies for preeclampsia associated with cardiovascular disease. Read Less

Cardiovascular disease is the leading cause of death among women in the United States, and women with hypertensive disorders of pregnancy have a 2-fold higher risk for cardiovascular disease later in life compared to women with uncomplicated pregnancies. This research investigates a patient-centered intervention during the postpartum period to promote engagement in cardiovascular preventive care. Read Less

The overall goal of this large, pragmatic, comparative effectiveness trial is to test the hypothesis that among at-risk individuals, 162 mg/day aspirin is superior to 81 mg/day in preventing Hypertensive disorders of pregnancy (HDP), and that there are multiple factors associated with adherence with aspirin therapy that will be important to identify to enable optimal implementation of study findings and population-level benefits. Read Less

Preeclampsia is a pregnancy disorder affecting \~5-10% of pregnancies in the United States. Women who develop preeclampsia during pregnancy are more likely to develop and die of cardiovascular disease later in life, even if they are otherwise healthy. The reason why this occurs is unclear but may be related to blood vessel damage and increased inflammation that occurs during the preeclamptic pregnancy and persists postpartum. Low dose aspirin (LDA; 75-150mg/daily) is currently the most effective and clinically accepted therapy for reducing preeclampsia prevalence in women at high risk for developing the syndrome. The purpose of this study is to interrogate the mechanisms by which LDA therapy mitigates persistent vascular dysfunction in postpartum women who have had preeclampsia. In this study, the investigators use the blood vessels in the skin as a representative vascular bed for examining mechanisms of microvascular dysfunction in humans. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) they examine the blood vessels in a dime-sized area of the skin in women who have had a history of preeclampsia. As a compliment to these measurements, they also draw blood from the subjects and isolate the inflammatory cells. Read Less

The researchers are testing a medication named ravulizumab for the treatment of severe preeclampsia and Hemolysis, Elevated Liver enzymes, Low Platelets (HELLP) syndrome. Read Less

Though cardiovascular disease (CVD) is the leading cause of mortality in women, traditional epidemiology in this area has focused on later life, when cardiometabolic risk has already exacted a cumulative toll on the vascular system. Recent data from the investigators and others has highlighted pregnancy as a unique, early moment of cardiovascular stress in young women that may "unmask" CVD propensity. It is unclear if PreE simply represents a "failed stress test" or directly contributes to the pathophysiology of future CVD. While mechanistic studies have largely been the purview of model-based studies, endothelial dysfunction has emerged as central to the pathogenesis of both PreE and peripartum cardiac dysfunction. Indeed, biomarkers of endothelial dysfunction and angiogenic imbalance during pregnancy have been shown to remain elevated at least 6 months post-partum. Moreover, peri-partum endothelial dysfunction can persist for years post-delivery and remains a significant risk factor for CVD (even after adjustment for other traditional risk factors). While these findings suggest that PreE-associated endothelial dysfunction and inflammation may contribute to early myocardial dysfunction that presages HF risk decades before its onset, the modifiable epidemiology of PreE-associated LVDD, including potential mechanisms of risk, remains unclear, limited by lack of precision molecular phenotypes accessible in a large number of American women across race. Ultimately, understanding the epidemiology and pathobiology of PreE-associated myocardial dysfunction affords a unique opportunity to identify women at risk with a longer lead-time for risk factor modification to interrupt CVD. The investigators hypothesize that persistent structural-functional myocardial alterations after PreE are linked to pre- and post-gravid cardiometabolic risk factors (SA1), functional and hemodynamic impairment (SA2) and select pathways of vascular and inflammatory stress relevant to HF risk (SA3). Despite extensive study on the role of inflammation/ischemia in PreE, there have been no large studies connecting these phenotypes with early PP functional response and biochemical alterations, a key barrier to designing studies for improving CVD/HF in women. SA1: To identify pregnancy-specific clinical factors related to postpartum HFpEF phenotypes Clinical Implication: Improve identification of women at highest risk for developing post-PreE LV diastolic dysfunction (a harbinger of HFpEF). SA2: To define functional and hemodynamic signatures of early HFpEF due to preeclampsia Clinical Implication: Identify women at highest risk for developing early HFpEF. SA3: To identify shared pathophysiologic mechanistic pathways for PreE-associated HFpEF Clinical Implication: Identify targetable pathways for post-PreE cardiac dysfunction that may prevent/ delay HFpEF development. Read Less

The goal of this proof-of-concept, case-control, clinical trial is to evaluate the efficacy of using two newer ultrasound technologies, quantitative ultrasound (QUS) and ultrafast power Doppler imaging (uPDI), to evaluate the health of the placenta, visualize blood flow through the placental vasculature by color Doppler imaging in singleton pregnancies with and without fetal growth restriction (FGR). * Our primary objective is to investigate the ability of using these ultrasound technologies to distinguish healthy pregnancies from those affected by FGR, a condition characterized by a fetal weight below the 10th percentile for the gestational age or abdominal circumference of the pregnancy. * Secondary aims include longitudinal evaluation of differences in QUS and uPDI imaging over gestation and changes in these measures with evolution of utero-placental insufficiency including with the development of abnormal umbilical-artery Doppler testing, diagnosis of severe FGR, identification of stillbirth, and detection of preeclampsia or preterm birth. Investigators will compare QUS/uPDI imaging and values in pregnancies determined to be healthy by approved, standard-of-care growth ultrasounds to those diagnosed with FGR. Participants will receive research ultrasounds with the experimental Verasonics Vantage 256 system (Verasonics, Inc, Kirkland, WA) utilizing uPDI/QUS every three weeks following their routine growth ultrasound evaluation until delivery. Demographic, obstetric, and delivery-related information, as well as portions of subjects' past medical history will be utilized by researchers to further contextualize imaging and variables gathered during the research ultrasounds. Read Less

A randomized controlled trial of 1,500 women to assess whether treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP) in pregnancy will result in a reduction in the rate of hypertensive disorders of pregnancy. Read Less

Women who develop preeclampsia during pregnancy are four times more likely to develop cardiovascular disease later in life, even if they are otherwise healthy. The reason why this occurs may be related to lasting blood vessel damage after the pregnancy but there are currently no specific treatment strategies to prevent this disease progression. This study addresses this public health issue by examining whether starting low dose aspirin therapy after pregnancy is an effective treatment for lasting blood vessel damage in order to inform better clinical management of cardiovascular disease risk in women who have had preeclampsia. Read Less