Comparative safety & effectiveness of antihypertensive medications in pregnancy

比较安全性

• 批准号: 8487519
• 负责人: Brian Thomas Bateman
• 金额: $ 13.72万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8487519
• 关键词: Address; Admission activity; Adrenergic beta-Antagonists; Age; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Bradycardia; Calcium Channel Blockers; Chronic; Clinical; Complement; Congenital Abnormality; Data; Data Set; Data Sources; Databases; Development; Discipline of obstetrics; Disease; Drug Utilization; Eclampsia; Education; Effectiveness; Epidemiologic Methods; Exposure to; Fetal Growth Retardation; Fetus; First Pregnancy Trimester; Goals; Guidelines; Health Services; Hospitals; Hypertension; Hypertension induced by pregnancy; Infant; Inferior; Institution; International; Link; Medicaid; Medical Records; Mentors; Morbidity - disease rate; Neonatal; Neonatal Hypoglycemia; Outpatients; Patients; Perinatal; Perinatal Exposure; Pharmaceutical Economics; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacy facility; Policies; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Public Health Schools; Records; Relative (related person); Research; Research Infrastructure; Research Personnel; Risk; Safety; Seizures; Source; Statistical Methods; Thiazide Diuretics; Training; United States; Universities; Woman; Work; base; cohort; comparative; comparative effectiveness; effectiveness research; fetal; high risk; hypertension control; hypertension treatment; inhibitor/antagonist; meetings; mortality; population based; prevent; public health relevance; reproductive; reproductive epidemiology

DESCRIPTION (provided by applicant): Hypertensive disorders complicate an estimated 6-8% of all pregnancies and are a significant source of fetal and maternal morbidity and mortality. Approximately 3-4% of all pregnant women will be exposed to antihypertensive medications during pregnancy. The antihypertensive most commonly used in pregnancy in the United States is methyldopa; however, it is an older, often poorly tolerated medication. It may be an inferior therapy with respect to important pregnancy outcomes compared to other classes of agents including alpha-beta blockers, beta blockers, and calcium channel blockers. Yet, for each of these other classes, important fetal safety concerns have been raised. The primary goal of the proposed project is therefore to evaluate the comparative safety and effectiveness of each of these commonly used agents relative to methyldopa. The clinical question this study aims to address is: "If a patient requires an outpatient antihypertensive during pregnancy for pre-existing or gestational hypertension, what is the safest agent for the fetus, and the one most likely to assure a good pregnancy outcome?" We will also examine the safety of first trimester exposure to thiazide diuretics and angiotensin converting enzyme inhibitors, which are the most common types of antihypertensives used in women of reproductive age outside of pregnancy and thus common first trimester exposures. This analysis will address the clinical question: "For a woman in whom pregnancy is planned or possible, which agents can be safely used given the potential for early fetal exposure to the medication?" The study will be performed using a pregnancy cohort obtained from the Medicaid Analytic Extract (MAX), a large population-based claims database. Using this dataset, we have developed a cohort of over 1.1 million pregnancies with longitudinal data that span from the pre-pregnancy to the postpartum periods. This cohort is linked to outpatient pharmacy claims and fetal records making it an exceptionally well-suited data source for the kind of study we propose. I will perform the proposed research within the well developed infrastructure of the Division of Pharmacoepidemiology and Pharmacoeconomics ("The Division") at the Brigham and Women's Hospital. The Division has a long track record of producing outstanding drug safety and effectiveness research using observational data sources. I will work with an interdisciplinary team of mentors and collaborators drawn from across institutions at Harvard University that have deep expertise and national/international reputations in epidemiological and statistical methods, perinatal pharmacoepidemiology, high-risk obstetrics, hypertensive diseases, and drug policy. This research work will be complemented by formal coursework at the Harvard School of Public Health and frequent seminars and lab meetings at the Division. This combination of intensive research, mentoring, and formal education will provide the necessary background for me to become a successful, independent researcher in obstetric pharmacoepidemiology.

描述（由申请人提供）：高血压疾病使估计 6-8% 的妊娠变得复杂，并且是胎儿和孕产妇发病和死亡的重要来源。大约 3-4% 的孕妇会在怀孕期间接触抗高血压药物。在美国，妊娠期最常用的抗高血压药物是甲基多巴；然而，它是一种较古老且耐受性较差的药物。与其他类别的药物（包括 α-β 阻滞剂、β 阻滞剂和钙通道阻滞剂）相比，就重要的妊娠结局而言，它可能是一种较差的治疗方法。然而，对于这些其他类别中的每一个，都提出了重要的胎儿安全问题。因此，拟议项目的主要目标是评估这些常用药物相对于甲基多巴的相对安全性和有效性。这项研究旨在解决的临床问题是：“如果患者在怀孕期间因已有高血压或妊娠期高血压而需要门诊抗高血压药物，那么对胎儿最安全、最有可能确保良好妊娠结局的药物是什么？”我们还将检查妊娠早期暴露于噻嗪类利尿剂和血管紧张素转换酶抑制剂的安全性，这些药物是妊娠期以外育龄妇女最常见的抗高血压药物类型，因此是妊娠早期常见的暴露情况。该分析将解决以下临床问题：“对于计划或可能怀孕的女性，考虑到胎儿早期接触药物的可能性，哪些药物可以安全使用？”该研究将使用从 Medicaid Analytic Extract (MAX)（一个基于人群的大型理赔数据库）获得的妊娠队列进行。使用该数据集，我们开发了超过 110 万次怀孕的队列，其中包含从怀孕前到产后的纵向数据。该队列与门诊药房索赔和胎儿记录相关，使其成为我们提议的研究类型的特别合适的数据源。我将在布莱根妇女医院药物流行病学和药物经济学部门（“该部门”）完善的基础设施内进行拟议的研究。该部门在利用观察数据源进行杰出的药物安全性和有效性研究方面有着悠久的记录。我将与来自哈佛大学各个机构的跨学科导师和合作者团队合作，他们在流行病学和统计方法、围产期药物流行病学、高危产科、高血压疾病和药物政策方面拥有深厚的专业知识和国内/国际声誉。这项研究工作将得到哈佛大学公共卫生学院的正式课程以及该部门频繁的研讨会和实验室会议的补充。这种深入研究、指导和正规教育的结合将为我成为一名成功的、独立的产科药物流行病学研究员提供必要的背景。