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孕期使用非阿司匹林类非甾体抗炎药与自然流产风险。

Use of nonaspirin nonsteroidal anti-inflammatory drugs during pregnancy and the risk of spontaneous abortion.

机构信息

Faculty of Pharmacy, University of Montreal, and the Research Center, Centre hospitalier universitaire Ste-Justine, Montréal, Quebec.

出版信息

CMAJ. 2011 Oct 18;183(15):1713-20. doi: 10.1503/cmaj.110454. Epub 2011 Sep 6.

Abstract

BACKGROUND

The association between the use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) during pregnancy and the risk of spontaneous abortion remains unclear because of inconsistent research results and the lack of evidence for an effect due to specific types or dosages of nonaspirin NSAIDs. We aimed to quantify the association between having a spontaneous abortion and types and dosages of nonaspirin NSAIDs in a cohort of pregnant women.

METHODS

Using a nested case-control design, we obtained data from the Quebec Pregnancy Registry for 4705 women who had a spontaneous abortion. For each instance, we randomly selected 10 controls from the remaining women in the registry who were matched by index date (date of the spontaneous abortion) and gestational age. Use of nonaspirin NSAIDs (identified by filled prescriptions) and nonuse were compared. We also looked for associations between different types and dosages of nonaspirin NSAIDs and having a spontaneous abortion. Analyses of associations and adjustment for confounding were done using conditional logistic regression.

RESULTS

We identified 4705 cases of spontaneous abortion (352 exposed [7.5%]); 47 050 controls (1213 exposed [2.6%]). Adjusting for potential confounders, the use of nonaspirin NSAIDs during pregnancy was significantly associated with the risk of spontaneous abortion (odds ratio [OR] 2.43, 95% confidence interval [CI] 2.12-2.79). Specifically, use of diclofenac (OR 3.09, 95% CI 1.96-4.87), naproxen (OR 2.64, 95% CI 2.13-3.28), celecoxib (OR 2.21, 95% CI 1.42-3.45), ibuprofen (OR 2.19, 95% CI 1.61-2.96) and rofecoxib (OR 1.83, 95% CI 1.24-2.70) alone, and combinations thereof (OR 2.64, 95% CI 1.59-4.39), were all associated with increased risk of spontaneous abortion. No dose-response effect was seen.

INTERPRETATION

Gestational exposure to any type or dosage of nonaspirin NSAIDs may increase the risk of spontaneous abortion. These drugs should be used with caution during pregnancy.

摘要

背景

由于研究结果不一致,且缺乏特定类型或剂量的非阿司匹林类 NSAIDs 产生影响的证据,因此,妊娠期间使用非阿司匹林类非甾体抗炎药(NSAIDs)与自然流产风险之间的关联仍不清楚。我们旨在定量评估孕妇自然流产与非阿司匹林类 NSAIDs 类型和剂量之间的关联。

方法

我们采用巢式病例对照设计,从魁北克妊娠登记处获取了 4705 名自然流产妇女的数据。对于每个病例,我们随机从登记处中剩余的、与索引日期(自然流产日期)和孕龄相匹配的 10 名对照中选择 1 名对照。比较使用和未使用非阿司匹林类 NSAIDs(通过填充分配处方确定)的情况。我们还研究了不同类型和剂量的非阿司匹林类 NSAIDs 与自然流产之间的关联。使用条件逻辑回归分析关联和调整混杂因素。

结果

我们确定了 4705 例自然流产病例(352 例暴露[7.5%]);47050 例对照(1213 例暴露[2.6%])。调整潜在混杂因素后,妊娠期间使用非阿司匹林类 NSAIDs 与自然流产风险显著相关(比值比[OR]2.43,95%置信区间[CI]2.12-2.79)。具体而言,使用双氯芬酸(OR3.09,95%CI1.96-4.87)、萘普生(OR2.64,95%CI2.13-3.28)、塞来昔布(OR2.21,95%CI1.42-3.45)、布洛芬(OR2.19,95%CI1.61-2.96)和罗非昔布(OR1.83,95%CI1.24-2.70)单药以及联合用药(OR2.64,95%CI1.59-4.39)均与自然流产风险增加相关。未观察到剂量-反应关系。

解释

妊娠期间接触任何类型或剂量的非阿司匹林类 NSAIDs 都可能增加自然流产的风险。这些药物在怀孕期间应谨慎使用。

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