Comparative safety & effectiveness of antihypertensive medications in pregnancy

比较安全性

• 批准号: 9039646
• 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/9039646
• 关键词: Address; Admission activity; Adrenergic beta-Antagonists; Age; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Bradycardia; Calcium Channel Blockers; Cesarean section; 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; Health Services; Hospitals; Hypertension; Infant; Inferior; Institution; International; Link; Maternal Mortality; Medicaid; Medical Records; Mentors; Neonatal; Neonatal Hypoglycemia; Neonatal Intensive Care Units; 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; Research; Research Infrastructure; Research Personnel; Risk; Safety; Seizures; Source; Statistical Methods; Thiazide Diuretics; Training; United States; Universities; Woman; Work; adverse pregnancy outcome; base; cohort; comparative; comparative effectiveness; effectiveness research; fetal; high risk; hypertension control; hypertension treatment; inhibitor/antagonist; maternal morbidity; meetings; population based; pregnancy hypertension; prevent; reproductive; reproductive epidemiology; Address; Admission activity; Adrenergic beta-Antagonists; Age; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Bradycardia; Calcium Channel Blockers; Cesarean section; 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; Health Services; Hospitals; Hypertension; Infant; Inferior; Institution; International; Link; Maternal Mortality; Medicaid; Medical Records; Mentors; Neonatal; Neonatal Hypoglycemia; Neonatal Intensive Care Units; 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; Research; Research Infrastructure; Research Personnel; Risk; Safety; Seizures; Source; Statistical Methods; Thiazide Diuretics; Training; United States; Universities; Woman; Work; adverse pregnancy outcome; base; cohort; comparative; comparative effectiveness; effectiveness research; fetal; high risk; hypertension control; hypertension treatment; inhibitor/antagonist; maternal morbidity; meetings; population based; pregnancy hypertension; prevent; 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）：高血压疾病使所有怀孕的6-8％复杂化，并且是胎儿和孕产妇发病率和死亡率的重要来源。在怀孕期间，所有孕妇中约有3-4％将接触到降压药。在美国怀孕中最常用的抗高血压是Methyldopa。但是，它是一种较旧的，通常耐受性不佳的药物。与其他类型的药物相比，这可能是关于重要妊娠结局的劣等疗法，包括α-beta阻滞剂，β受体阻滞剂和钙通道阻滞剂。但是，对于其他每个类别，都提出了重要的胎儿安全问题。因此，该项目的主要目标是评估这些常用药物相对于甲基多帕的每种药物的比较安全性和有效性。该研究旨在解决的临床问题是：“如果患者在怀孕期间需要门诊抗高血压才能先前或妊娠高血压，那么胎儿最安全的药物是什么，而最有可能确保良好怀孕结果的药物是什么？”我们还将研究孕中期暴露于噻嗪类利尿剂和血管紧张素转化酶抑制剂的安全性，这些酶抑制剂是最常见的抗高血压类型，用于妊娠以外的生殖年龄妇女，因此是常见的首先妊娠中期孕生。该分析将解决一个临床问题：“对于计划或可能怀孕的妇女，可以安全地使用哪些特工，因为可能会早期胎儿暴露于药物治疗中？”这项研究将使用从医疗补助分析提取物（MAX）获得的妊娠队列进行，这是一个庞大的基于人群的索赔数据库。使用此数据集，我们已经开发了超过110万例妊娠的队列，这些妊娠和纵向数据遍及从怀孕前到产后时期。该队列与门诊药房索赔和胎儿记录有关，这使其成为我们提出的研究类型的非常适合的数据源。我将在Brigham and Hospital的药物ePidemiology and Pharmacocoecocoecocoecopoymensics（“部门”）的良好开发基础设施中进行拟议的研究。该部门在使用观察数据源产生出色的药物安全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机构的导师和合作者组成的跨学科团队，他们在流行病学和统计方法，围产期药物疾病，高风险妇产科，高级疾病，高血压疾病和药物政策方面具有深厚的专业知识和国家/国际声誉。这项研究工作将在哈佛公共卫生学院的正式课程以及该部门的频繁研讨会和实验室会议上得到补充。强化研究，指导和正规教育的这种结合将为我提供必要的背景，使我成为成功，独立的药物ePidemiology的独立研究人员。