Early Double Low-Dose Aspirin to Reduce Preeclampsia and Miscarriage: a Global Approach RCT

项目摘要 阿司匹林目前被推荐在怀孕期间帮助预防先兆子痫，而且也显示出 防止妊娠丢失。先兆子痫是妊娠的一种危险的并发症，它使 孕妇及其婴儿有严重发病和死亡的风险，而妊娠丢失是最常见的 妊娠并发症估计会影响所有妊娠的20%-30%。来自世界卫生组织的当前临床指南 美国预防服务工作组(USPSTF)建议每天使用婴儿阿司匹林(81毫克)，从 妊娠12周，预防先兆子痫。然而，数据表明，更早开始服用阿司匹林和 剂量越高，可能会产生更好的保护作用。此外，怀孕后立即开始服用阿司匹林 认知可以最大限度地发挥对先兆子痫的影响，同时也提供了额外的机会来预防 妊娠丢失。因此，我们建议进行一项随机试验，以调查每日“双低”是否 剂量“阿司匹林治疗(162毫克/天)在首次妊娠试验阳性(最多6周)时开始。 怀孕)可能有助于预防这两种结果。通过对所有参与者的跟踪，对参与者进行临床招募 整个宾夕法尼亚医学系统的初步怀孕测试将确保早期检测的可行性 怀孕，使妊娠丢失监测和启动试验干预。由此得出的结论是 这项研究将在不同的美国孕妇样本中提供必要的、高质量的证据，以供 妊娠期间阿司匹林临床使用指南的潜在变化。我们将(目标1)确定 阿司匹林(剂量162毫克)在妊娠试验阳性(怀孕6周以下)后开始治疗，与 不同人群对先兆子痫的标准护理(孕12周开始服用81毫克)；(目标2) 确定妊娠试验阳性(最长6周)开始服用阿司匹林(剂量162毫克)的效果 与标准护理(怀孕12周开始剂量81毫克)在妊娠丢失方面的比较 多样化的人群；以及(目标3)确定可能从“双低剂量”阿司匹林中获益最多的表型(162 MG)在受孕后不久开始使用机器学习，以提供更有针对性的治疗方案，以实现最优的整体 妊娠结局。作为一种安全、负担得起的干预措施，这些发现将立即产生翻译价值 为了改善孕妇的生育结果，包括极大地改善黑人妇女等少数族裔 在当前数据中未得到充分体现。

Project Summary Aspirin is currently recommended during pregnancy to help prevent preeclampsia, and also shows promise for protecting against pregnancy loss. Preeclampsia is a dangerous complication of pregnancy that puts both the pregnant person and their baby at risk of serious morbidity and death, and pregnancy loss is the most common complication of pregnancy estimated to affect 20-30% of all conceptions. Current clinical guidelines from the U.S. Preventive Services Task Force (USPSTF) recommend the use of daily “baby” aspirin (81 mg), begun at 12 weeks' gestation, to prevent preeclampsia. However, data suggest that even earlier initiation of aspirin and at higher doses may result in greater protection. Furthermore, initiating aspirin immediately upon pregnancy recognition may maximize effects on preeclampsia while also providing the added opportunity to prevent pregnancy loss. Therefore, we propose to conduct a randomized trial to investigate whether daily “double low- dose” aspirin therapy (162 mg per day) initiated at the time of first positive pregnancy test (up to 6 weeks' gestation) may help prevent both outcomes. Clinical recruitment of participants through the follow-up of all initial pregnancy tests throughout the Penn Medicine system will ensure feasibility for early detection of pregnancy, enabling pregnancy loss monitoring and initiation of the trial intervention. The findings from this study will provide essential, high-quality evidence in a diverse sample of U.S. pregnant people to inform potential changes to clinical guidelines for aspirin use in pregnancy. We will (Aim 1) determine the effect of aspirin treatment (dose 162 mg) initiated upon positive pregnancy test (up to 6 weeks' gestation) compared to standard of care (dose 81 mg initiated at 12 weeks' gestation) on preeclampsia in a diverse population; (Aim 2) determine the effect of aspirin treatment (dose 162 mg) initiated upon positive pregnancy test (up to 6 weeks' gestation) compared to standard of care (dose 81 mg initiated at 12 weeks' gestation) on pregnancy loss in a diverse population; and (Aim 3) identify phenotypes who may benefit most from “double low-dose” aspirin (162 mg) begun soon after conception, using machine learning, to inform more targeted therapy for optimal overall pregnancy outcomes. As a safe, affordable intervention, these findings will have immediate translational value to improve reproductive outcomes in pregnant patients, including minorities such as Black women vastly underrepresented in current data.