Impact of maternal aspirin therapy on the maternal/fetal unit at delivery: A study of aspirin pharmacokinetics, pharmacodynamics, and pharmacogenomics through pregnancy

项目总结 背景：虽然关于阿司匹林治疗子痫前期疗效的研究很多 预防有关阿司匹林的个体差异的信息很少。 治疗，这种变化如何通过妊娠，以及下游新生儿的影响 母性治疗。 目的：该提案有两个目的：研究阿司匹林反应的个体预测因素。 通过怀孕过程和阿司匹林治疗对产妇/新生儿病房的影响。 最终，我们的结果将探索一种常见的基因变异，这种变异可能会导致 阿司匹林治疗的结果和反应，确定与阿司匹林相关的新生儿表观遗传学变化 治疗和HDP可以阐明阿司匹林治疗对后代的长期影响，并进一步 描述孕期阿司匹林的药理特征以指导给药。 目的1：建立分娩样本队列，以评估阿司匹林对 分娩时母体/胎儿单位，以及PAR4基因、HDP和个体因素如何改变 观察到的效果 目的2：阿司匹林在孕妇体内的药代动力学和药效学纵向评价 子痫前期高危患者 方法：本方案采用双管齐下的研究设计。目标1将通过 招募托马斯·杰斐逊大学医院入院分娩的病人。这个 对这一队列感兴趣的暴露将是阿司匹林，并计划进行嵌套病例/对照研究 那些有和没有被诊断为妊娠高血压疾病(HDP)的人。目标2将是一个 在前三个月登记的现有R21队列基础上纵向增加，以包括第三个 阿司匹林药代动力学/药效学(PK/PD)的三个月评估及其方法 孕期影响阿司匹林PK/PD的个体因素。

PROJECT SUMMARY 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.