Background: While there has been much research on efficacy of aspirin for preeclampsia prevention there is little information on the individual variability in response to aspirin therapy, how this changes through gestation, and downstream neonatal impact of maternal therapy. OBJECTIVE: This proposal has two aims to study the individual predictors of response to aspirin through the course of pregnancy and the impact of aspirin therapy on the maternal/neonatal unit. Ultimately our results will explore a common genetic variant that may drive racial disparities in outcomes and response to aspirin therapy, identify neonatal epigenetic changes related to aspirin therapy and HDP that could elucidate long term impact of aspirin therapy on offspring, and further characterize aspirin pharmacology in pregnancy to guide dosing.
Aim 1 : Development of delivery sample cohort to evaluate the impact of aspirin on the maternal/fetal unit at delivery, and how PAR4 genotype, HDP, and individual factors may modify the observed effect Aim 2: Longitudinal evaluation of pharmacokinetics and pharmacodynamics of aspirin in pregnant patients at high risk for preeclampsia Methods: This proposal has a two-pronged study design.
Aim 1 will be conducted through recruitment of patients admitted for delivery at Thomas Jefferson University Hospital. The exposure of interest in this cohort will be aspirin, with a planned nested case/control study of those with and without a diagnosis of hypertensive disorder of pregnancy (HDP).
Aim 2 will be a longitudinal addition to an existing R21cohort enrolled in the first trimester to include a third trimester assessment of pharmacokinetics/pharmacodynamics (PK/PD) of aspirin and how individual factors impact aspirin PK/PD in pregnancy.
Hypertensive disorders of pregnancy (HDP), preeclampsia and gestational hypertension, are one of the most common causes of pregnancy related major maternal and neonatal morbidity and mortality. This proposal addresses thus far understudied aspects of aspirin pharmacology in preeclampsia prevention through 1) a novel study on pharmacogenomics of aspirin and hypertensive disorders of pregnancy that has implications for the management of an at risk minority population, 2) using case/control with groups with and without HDP and with and without aspirin to understand the impact of aspirin therapy on the maternal/fetal unit and potential long term impact on offspring and 3) evaluating how individual factors and advancing gestation affect aspirin pharmacology/efficacy through pregnancy. Ultimately our results will explore a common genetic variant that may drive racial disparities in outcomes and response to aspirin therapy, identify neonatal epigenetic changes related to aspirin therapy and HDP that could elucidate long term impact of aspirin therapy on offspring, and further characterize aspirin pharmacology in pregnancy to guide dosing.