Prenatal NSAID Use and Miscarriage

描述（由申请人提供）：最近的报告显示，妊娠期间使用非甾体抗炎药（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医疗保健计划（KPMCP）的成员中进行一项队列研究。所有在13家KPMCP机构之一进行妊娠试验呈阳性且会说英语或西班牙语的KPMCP妇女将接受妊娠期间使用非甾体抗炎药的筛查，以确定暴露于非甾体抗炎药的妇女。使用早期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妇女和500名未暴露妇女；为了控制适应症的混淆，我们还将招募500名使用过对乙酰氨基酚，但既不使用非甾体抗炎药也不使用阿司匹林的妇女，因为对乙酰氨基酚与非甾体抗炎药有许多相似的适应症，但药理作用不同。一旦确定阳性妊娠，产前使用非甾体抗炎药和其他药物的详细信息将在面对面访谈中确定。随访后是否使用非甾体抗炎药将在妊娠结束或妊娠20周时进一步确定。自我报告的非甾体抗炎药使用情况将通过药瓶、处方记录和KPMCP药房数据库确认，这些数据库包含在KPMCP药房获得的所有处方非甾体抗炎药和非处方非甾体抗炎药。将通过与KPMCP数据库的联系和对医疗记录的审查来确定自然流产和其他妊娠结果。未确定的妊娠结局将通过随访电话访谈确定。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，还将检查与NSAID使用剂量、时间和持续时间相关的风险，以及NSAID使用的其他特征，包括当前/过去使用和累积剂量。拟议的研究将是第一个以人群为基础的前瞻性队列研究，专门用于检查与产前使用非甾体抗炎药相关的自然流产风险。由于非甾体抗炎药在普通人群和育龄妇女中的广泛使用，本研究的结果将为围孕期使用非甾体抗炎药的安全性提供有价值的信息，这对公共卫生具有重要意义。

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.