Prenatal NSAID Use and Miscarriage

描述(由申请人提供)：最近的报告显示，在怀孕期间使用非类固醇抗炎药(NSAIDs)会增加自然流产的风险。为了进一步研究这种关联，我们建议在Kaiser Permanente Medical Care Program(KPMCP)的成员中进行一项队列研究。所有在毕马威13家机构中的一家进行了阳性妊娠测试的毕马威妇女，如果会说英语或西班牙语，都将接受孕期使用非类固醇抗炎药的筛查，以确定接触非类固醇抗炎药的妇女。利用早先在电磁场暴露与自然流产风险研究中开发的方法，我们将招募1500名孕妇：500名非甾体抗炎药暴露的妇女和500名未暴露于非甾体抗炎药的妇女；为了通过适应症控制混淆，我们还将招募500名使用过对乙酰氨基酚的妇女，但既不使用非甾体抗炎药，也不使用阿司匹林，因为对乙酰氨基酚与非甾体抗炎药有许多相似的适应症，但具有不同的药理作用。一旦确认阳性妊娠，将在面谈中尽快确定有关产前使用非甾体抗炎药和其他药物的详细信息。面谈后任何后续使用非甾体抗炎药的情况将在怀孕结束或怀孕20周时进一步确定。自行报告的非处方药使用情况将由药瓶、处方记录和毕马威药房数据库确认，这些数据库收集了毕马威药店获得的所有处方药和非处方药。将通过与毕马威会计师事务所数据库的链接和对医疗记录的审查来确定自然流产和其他妊娠结局。不明身份的妊娠结局将通过后续电话采访来确定。COX比例风险回归将用于检查与围孕期使用非甾体抗炎药相关的自然流产风险。此外，还将审查与非类固醇抗炎药的剂量、时间和持续时间相关的风险，以及非类固醇抗炎药的其他使用特征，包括当前/过去的使用情况和累积剂量。这项拟议的研究将是第一项基于人群的前瞻性队列研究，专门设计用于检查与产前使用非甾体抗炎药相关的自然流产风险。这项研究的结果将提供关于围产期使用非类固醇抗炎药的安全性的宝贵信息，由于非类固醇抗炎药在普通人群和育龄妇女中的广泛使用，非类固醇抗炎药具有重大的公共卫生影响。

DESCRIPTION (provided by applicant): Recent reports have revealed an increased risk of spontaneous abortion associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy. To further examine this association, we propose to conduct a cohort study among the members of the Kaiser Permanente Medical Care Program (KPMCP). All KPMCP women who have a positive pregnancy test performed in one of the 13 KPMCP facilities and who speak either English or Spanish will be screened for their NSAID use during pregnancy to identify NSAID-exposed women. Using methods developed in an earlier study of electromagnetic field exposure and the risk of spontaneous abortion, we will recruit 1500 pregnant women: 500 NSAID-exposed women and 500 unexposed women; to control for confounding by indication, we will also recruit 500 women who have used acetaminophen, but neither NSAIDs nor aspirin because acetaminophen shares many similar indications with NSAIDs, but has a different pharmacological effect. Detailed information on prenatal NSAID use and other medications will be ascertained during an in-person interview as soon as the positive pregnancy is identified. Any subsequent NSAID use after the interview will be further ascertained at the end of pregnancy or at 20 weeks of gestation. Self-reported NSAID use will be confirmed by medication bottles, prescription records, and the KPMCP pharmacy databases that capture all prescription NSAIDs and nonprescription NSAID obtained at KPMCP pharmacies. Spontaneous abortion and other pregnancy outcomes will be ascertained through linkage to the KPMCP databases and review of medical records. Unidentified pregnancy outcomes will be ascertained through follow-up telephone interviews. Cox proportional hazard regression will be used to examine the risk of spontaneous abortion associated with periconceptional NSAID use. In addition, the risk associated with dose, timing, and duration of NSAID use as well as other characteristics of NSAID use including current/past use and cumulative dose will be examined. The proposed study will be the first population-based prospective cohort study specifically designed to examine the risk of spontaneous abortion associated with prenatal NSAID use. The findings from this study will provide valuable information on the safety of periconceptional NSAID use that has significant public health implications because of the widespread use of NSAIDs in the general population and among women of reproductive age.