A Study of Preeclampsia Recurrence

About This Grant

PROJECT SUMMARY/ABSTRACT Preeclampsia is a leading cause of maternal morbidity, maternal mortality, and iatrogenic preterm birth. Individuals at the highest risk for developing preeclampsia are those who had it in a prior pregnancy. However, not everyone recurs. Presentations of preeclampsia are heterogeneous, spanning from patients who spend weeks in the hospital prior to an extreme preterm birth to patients who are diagnosed incidentally during spontaneous, term labor. A major knowledge gap is understanding how variations in preeclampsia presentations relate to recurrence risk. This proposal outlines a research and training plan focused on studying drivers of preeclampsia recurrence with the goal of identifying strategies for mitigating risk. Aim 1 is to determine the relationship between subtypes of preeclampsia and risk of recurrence in a population representative of the United States. Aim 2 is to delineate the role of modifiable and non-modifiable risk factors in preeclampsia recurrence. This proposal leverages resources at Vanderbilt University Medical Center (VUMC) to achieve these aims. Clinical information and genetic data on over 12,900 patients receiving care at VUMC for two or more pregnancies are available for this analysis. Vanderbilt’s Precision Phenotyping Core will be utilized in the development and validation of algorithms for identifying preeclampsia subtypes in the electronic health record (EHR). Advanced quantitative methods will be used to determine risk of recurrence by preeclampsia subtypes, by heritability of disease quantified using a polygenic risk score, and by selected modifiable and non-modifiable risk factors including interpregnancy interval, interpregnancy weight gain, maternal smoking status, maternal age, and fetal sex. A major focus of this proposal is to support Dr. Sundermann’s career development. Her long-term career goal is to conduct epidemiologic and translational research that provides evidence around modifiable determinants of adverse pregnancy outcomes to identify targets for interventions as an independent physician-scientist in obstetrics and gynecology. She will accomplish this goal through training focused on gaining expertise in clinical informatics, reproductive epidemiology methods, and genetic analysis. The research environment for this proposal is excellent. Dr. Sundermann has full departmental and institutional support and access to VUMC’s shared resources for training and research. Her mentorship committee includes experts in obstetrics, genetic epidemiology, reproductive epidemiology, biomedical informatics, and biostatistics. This K01 will support work that delivers insight into the recurrence of one of the most common and morbid conditions of pregnancy while providing training that will serve as a vehicle for Dr. Sundermann’s transition to independence.