Preconception low-dose aspirin and pregnancy outcomes: results from the EAGeR randomised trial
Preconception low-dose aspirin and pregnancy outcomes: results from the EAGeR randomised trial
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DOI：
10.1016/s0140-6736(14)60157-4
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发表时间：
2014-07-05
期刊：
影响因子：
168.9
通讯作者：
Galai, Noya
中科院分区：
文献类型：
--
作者：
Schisterman, Enrique F.;Silver, Robert M.;Galai, Noya
背景：孕前诱发的低剂量阿司匹林可能对妊娠结局有积极影响，但这种可能性尚未得到充分评估。我们的目的是调查低剂量阿司匹林是否能提高曾有一至两次流产的妇女的活产率。方法在这项多中心、块随机、双盲、安慰剂对照试验中，从美国四家医疗中心招募年龄在18-40岁、试图怀孕的女性。参与者根据资格标准分层-原始阶层仅限于前一年妊娠少于20周的一次损失的妇女，而扩大的阶层包括以前有一到两次损失的妇女，没有胎龄或损失时间的限制。妇女按中心和资格阶层按1:1的比例进行分组随机。怀孕前每日低剂量阿司匹林（每天81毫克）加叶酸与安慰剂加叶酸长达6个月经周期进行比较；对于怀孕的妇女，研究治疗持续到妊娠36周。参与者、试验工作人员和调查人员被蒙面接受指定的治疗。主要终点为活产率，并通过治疗意向进行分析。该试验已在ClinicalTrials.gov注册，注册号为NCT00467363。总体而言，在2007年6月15日至2011年7月15日期间，随机招募了1228名女性，其中1078人完成了试验并被纳入分析（535人在低剂量阿司匹林组，543人在安慰剂组）。低剂量阿司匹林组有309名（58%）妇女活产，而安慰剂组有286名（53%）妇女活产（p=0.0984；活产率的绝对差异为5.09% [95% CI - 0.84 ~ 11.02]）。低剂量阿司匹林组有68例（13%）妇女妊娠失败，而安慰剂组有65例（12%）妇女妊娠失败（p=0.7812）。在原始人群中，低剂量阿司匹林组的242名妇女中有151名（62%）活产，而安慰剂组的250名妇女中有133名（53%）活产（p=0.0446；活产率的绝对差异为9.20%[0.51至17.89]）。在扩张层中，低剂量阿司匹林组的293名妇女中有158名（54%）活产，安慰剂组的293名妇女中有153名（52%）活产（p=0.7406，活产率绝对差异为1.71%[-6.37 ~ 9.79]）。两组间主要不良事件相似。低剂量阿司匹林与阴道出血增加有关，但这种不良事件与妊娠丢失无关。解释怀孕前低剂量阿司匹林与有1 - 2次妊娠失败的妇女的活产或妊娠失败无显著相关。然而，在前一年妊娠不到20周的妇女中，单次记录丢失的活产率较高。低剂量阿司匹林不建议用于预防流产。资助尤尼斯·肯尼迪·施莱弗国家儿童健康与人类发展研究所（美国国家卫生研究院）。
Background Preconception-initiated low-dose aspirin might positively affect pregnancy outcomes, but this possibility has not been adequately assessed. Our aim was to investigate whether low-dose aspirin improved livebirth rates in women with one to two previous pregnancy losses.Methods In this multicentre, block-randomised, double-blind, placebo-controlled trial, women aged 18-40 years who were attempting to become pregnant were recruited from four medical centres in the USA. Participants were stratified by eligibility criteria-the original stratum was restricted to women with one loss at less than 20 weeks' gestation during the previous year, whereas the expanded stratum included women with one to two previous losses, with no restrictions on gestational age or time of loss. Women were block-randomised by centre and eligibility stratum in a 1: 1 ratio. Preconception-initiated daily low-dose aspirin (81 mg per day) plus folic acid was compared with placebo plus folic acid for up to six menstrual cycles; for women who conceived, study treatment continued until 36 weeks' gestation. Participants, trial staff, and investigators were masked to the assigned treatment. The primary outcome was livebirth rate, which was analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00467363.Findings Overall, 1228 women were recruited and randomly assigned between June 15, 2007, and July 15, 2011, 1078 of whom completed the trial and were included in the analysis (535 in the low-dose aspirin group and 543 in the placebo group). 309 (58%) women in the low-dose aspirin group had livebirths, compared with 286 (53%) in the placebo group (p=0.0984; absolute difference in livebirth rate 5.09% [95% CI - 0.84 to 11.02]). Pregnancy loss occurred in 68 (13%) women in the low-dose aspirin group, compared with 65 (12%) women in the placebo group (p=0.7812). In the original stratum, 151 (62%) of 242 women in the low-dose aspirin group had livebirths, compared with 133 (53%) of 250 in the placebo group (p=0.0446; absolute difference in livebirth rate 9.20% [0.51 to 17 89]). In the expanded stratum, 158 (54%) of 293 women in the low-dose aspirin group and 153 (52%) of 293 in the placebo group had livebirths (p=0.7406; absolute difference in livebirth rate 1.71% [-6.37 to 9.79]). Major adverse events were similar between treatment groups. Low-dose aspirin was associated with increased vaginal bleeding, but this adverse event was not associated with pregnancy loss.Interpretation Preconception-initiated low-dose aspirin was not significantly associated with livebirth or pregnancy loss in women with one to two previous losses. However, higher livebirth rates were seen in women with a single documented loss at less than 20 weeks' gestation during the previous year. Low-dose aspirin is not recommended for the prevention of pregnancy loss.Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development (US National Institutes of Health).