Non-steroidal anti-inflammatory use and miscarriage

非甾体抗炎药的使用和流产

• 批准号: 7447624
• 负责人: KATHERINE E HARTMANN
• 金额: $ 22.46万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7447624
• 关键词: clinical research; disease /disorder proneness /risk; drug administration rate /duration; embryo /fetus drug adverse effect; embryo /fetus monitoring; female; gestational age; human pregnant subject; human subject; interview; karyotype; nonsteroidal antiinflammatory agent; personal log /diary; spontaneous abortion; ultrasonography; women' s health

DESCRIPTION (provided by applicant): Thirty-nine percent of reproductive age women have used a non-steroidal anti-inflammatory drug (NSAID) in the past week, and NSAIDs are the most frequent medication exposure in the first trimester of pregnancy. The safety of NSAID use in early pregnancy is uncertain. Our objective is to examine prospectively the association of NSAID use with spontaneous abortion. We propose to enroll women who are planning a pregnancy and obtain daily diaries of medication use, symptoms (indications) and other key confounders during the period while participants are attempting to conceive. Among the first 1,200 women who become pregnant, we will continue to collect daily diary information through the 12th week of pregnancy, obtain an early pregnancy ultrasound in the sixth week, and conduct an extensive computer assisted telephone interview at 13 weeks. Birth outcomes will be documented for all pregnancies and karyotyping will be done on all losses where a tissue specimen is available. These methods will allow us to answer our primary research questions: (1) Is NSAID use independently associated with increased risk of spontaneous abortion? (2) Does the association of NSAIDs with spontaneous abortion depend on cumulative dose, regular versus episodic use, and/or exposure during critical developmental windows? and these secondary questions: (3) Are common indications for NSAID use independently associated with spontaneous abortion? (4) Does developmental stage attained prior to spontaneous abortion differ between exposed and unexposed pregnancies? The primary tools for the proposed study are already in place including successful approaches to community-based recruitment prior to pregnancy, ultrasound forms and protocols, computer assisted telephone interviews, data management and quality control systems and experienced staff. Costly piloting and implementation phases have been completed. In short, we are fully prepared to efficiently address pressing questions about NSAID exposure in early pregnancy by conducting a large-scale, fully-prospective cohort study. If NSAID use has an adverse effect on early pregnancy outcomes, the public health impact would be substantial. For example, if NSAID exposure increases relative risk by 50 per cent, and 19 per cent of women use NSAIDs during the first trimester of pregnancy (a conservative estimate based on retrospective data), then over 80,000 spontaneous abortions could be attributed to NSAIDs each year in the United States.

描述（由申请人提供）：39%的育龄妇女在过去一周内使用了非甾体抗炎药（NSAID），非甾体抗炎药是妊娠前三个月最常见的药物暴露。妊娠早期使用非甾体抗炎药的安全性尚不确定。我们的目的是前瞻性地研究使用非甾体抗炎药与自然流产的关系。我们建议招募计划怀孕的妇女，并在参与者试图怀孕期间获取药物使用、症状（指征）和其他关键混杂因素的每日日记。在首批1200名怀孕的妇女中，我们将在怀孕第12周继续收集每日日记信息，在怀孕第6周获得早期妊娠超声，并在第13周进行广泛的计算机辅助电话访谈。将记录所有妊娠的出生结果，并在有组织标本的情况下对所有损失进行核型分析。这些方法将使我们能够回答我们的主要研究问题：(1)非甾体抗炎药的使用是否与自然流产风险增加独立相关？(2)非甾体抗炎药与自然流产的关联是否取决于累积剂量、定期使用还是间歇性使用和/或关键发育窗口期的暴露？以及这些次要问题：(3)非甾体抗炎药的常见适应症是否与自然流产独立相关？(4)暴露妊娠和未暴露妊娠在自然流产前达到的发育阶段是否不同？拟议研究的主要工具已经到位，包括在怀孕前以社区为基础征聘人员的成功方法、超声波表格和规程、计算机辅助电话访谈、数据管理和质量控制系统以及经验丰富的工作人员。成本高昂的试点和实施阶段已经完成。简而言之，我们已经做好充分准备，通过开展一项大规模、全前瞻性队列研究，有效地解决有关妊娠早期非甾体抗炎药暴露的紧迫问题。如果非甾体抗炎药的使用对早期妊娠结果有不利影响，公共卫生影响将是巨大的。例如，如果非甾体抗炎药暴露增加了50%的相对风险，并且19%的妇女在怀孕的前三个月使用非甾体抗炎药（基于回顾性数据的保守估计），那么在美国每年有超过80,000例自然流产可归因于非甾体抗炎药。