Department of Obstetrics and Gynecology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
N Engl J Med. 2010 Apr 29;362(17):1586-96. doi: 10.1056/NEJMoa1000641. Epub 2010 Mar 24.
Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs.
In this randomized trial, we enrolled 364 women between the ages of 18 and 42 years who had a history of unexplained recurrent miscarriage and were attempting to conceive or were less than 6 weeks pregnant. We then randomly assigned them to receive daily 80 mg of aspirin plus open-label subcutaneous nadroparin (at a dose of 2850 IU, starting as soon as a viable pregnancy was demonstrated), 80 mg of aspirin alone, or placebo. The primary outcome measure was the live-birth rate. Secondary outcomes included rates of miscarriage, obstetrical complications, and maternal and fetal adverse events.
Live-birth rates did not differ significantly among the three study groups. The proportions of women who gave birth to a live infant were 54.5% in the group receiving aspirin plus nadroparin (combination-therapy group), 50.8% in the aspirin-only group, and 57.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, -2.6 percentage points; 95% confidence interval [CI], -15.0 to 9.9; aspirin only vs. placebo, -6.2 percentage points; 95% CI, -18.8 to 6.4). Among 299 women who became pregnant, the live-birth rates were 69.1% in the combination-therapy group, 61.6% in the aspirin-only group, and 67.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, 2.1 percentage points; 95% CI, -10.8 to 15.0; aspirin alone vs. placebo -5.4 percentage points; 95% CI, -18.6 to 7.8). An increased tendency to bruise and swelling or itching at the injection site occurred significantly more frequently in the combination-therapy group than in the other two study groups.
Neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate, as compared with placebo, among women with unexplained recurrent miscarriage. (Current Controlled Trials number, ISRCTN58496168.)
对于不明原因复发性流产的女性，常处方使用阿司匹林和低分子肝素，以提高活产率，但随机对照试验的有限数据支持使用这些药物。
在这项随机试验中，我们纳入了 364 名年龄在 18 至 42 岁之间、有不明原因复发性流产史且正在尝试受孕或妊娠不足 6 周的女性，将她们随机分配至每日接受 80mg 阿司匹林加开放性标签皮下那屈肝素（起始剂量为 2850IU，一旦证实妊娠即开始）、仅接受 80mg 阿司匹林或安慰剂治疗。主要结局指标为活产率。次要结局指标包括流产率、产科并发症以及母婴不良事件。
三组研究之间的活产率无显著差异。接受阿司匹林加那屈肝素治疗的女性活产率为 54.5%（联合治疗组），仅接受阿司匹林治疗的女性活产率为 50.8%，安慰剂组为 57.0%（活产率的绝对差异：联合治疗组 vs. 安慰剂组，-2.6 个百分点；95%置信区间 [CI]，-15.0 至 9.9；阿司匹林组 vs. 安慰剂组，-6.2 个百分点；95% CI，-18.8 至 6.4）。在 299 名妊娠的女性中，联合治疗组的活产率为 69.1%，阿司匹林组为 61.6%，安慰剂组为 67.0%（活产率的绝对差异：联合治疗组 vs. 安慰剂组，2.1 个百分点；95% CI，-10.8 至 15.0；阿司匹林组 vs. 安慰剂组，-5.4 个百分点；95% CI，-18.6 至 7.8）。与其他两组相比，联合治疗组中淤青和肿胀或注射部位瘙痒/过敏的发生率显著增加。
与安慰剂相比，阿司匹林联合那屈肝素或阿司匹林单药治疗并未提高不明原因复发性流产女性的活产率。（当前对照试验编号：ISRCTN58496168。）
