Harris Birthright Research Centre of Fetal Medicine, Fetal Medicine Research Institute, King's College Hospital, London, UK.
Department of Obstetrics and Gynecology & Department of Social and Preventive Medicine, Faculty of Medicine, Université Laval, Quebec City, Qc, Canada.
Am J Obstet Gynecol. 2018 May;218(5):483-489. doi: 10.1016/j.ajog.2017.12.238. Epub 2018 Jan 3.
Impaired placentation in the first 16 weeks of pregnancy is associated with increased risk of subsequent development of preeclampsia, birth of small-for-gestational-age neonates, and placental abruption. Previous studies reported that prophylactic use of aspirin reduces the risk of preeclampsia and small-for-gestational-age neonates with no significant effect on placental abruption. However, meta-analyses of randomized controlled trials that examined the effect of aspirin in relation to gestational age at onset of therapy and dosage of the drug reported that significant reduction in the risk of preeclampsia and small-for-gestational-age neonates is achieved only if the onset of treatment is at ≤16 weeks of gestation and the daily dosage of the drug is ≥100 mg.
We aimed to estimate the effect of aspirin on the risk of placental abruption or antepartum hemorrhage in relation to gestational age at onset of therapy and the dosage of the drug.
To perform a systematic review and meta-analysis of randomized controlled trials that evaluated the prophylactic effect of aspirin during pregnancy, we used PubMed, Cinhal, Embase, Web of Science and Cochrane library from 1985 to September 2017. Relative risks of placental abruption or antepartum hemorrhage with their 95% confidence intervals were calculated with the use of random effect models. Analyses were stratified according to daily dose of aspirin (<100 and ≥100 mg) and the gestational age at the onset of therapy (≤16 and >16 weeks of gestation) and compared with the use of subgroup difference analysis.
The entry criteria were fulfilled by 20 studies on a combined total of 12,585 participants. Aspirin at a dose of <100 mg per day had no impact on the risk of placental abruption or antepartum hemorrhage, irrespective of whether it was initiated at ≤16 weeks of gestation (relative risk, 1.11; 95% confidence interval, 0.52-2.36) or at >16 weeks of gestation (relative risk, 1.32; 95% confidence interval, 0.73-2.39). At ≥100 mg per day, aspirin was not associated with a significant change on the risk of placental abruption or antepartum hemorrhage, whether the treatment was initiated at ≤16 weeks of gestation (relative risk, 0.62, 95% confidence interval, 0.31-1.26), or at >16 weeks of gestation (relative risk, 2.08; 95% confidence interval, 0.86-5.06), but the difference between the subgroups was significant (P=.04).
Aspirin at a daily dose of ≥100 mg for prevention of preeclampsia that is initiated at ≤16 weeks of gestation, rather than >16 weeks, may decrease the risk of placental abruption or antepartum hemorrhage.
妊娠 16 周内胎盘功能不全与子痫前期、小于胎龄儿和胎盘早剥的发生风险增加有关。既往研究表明，阿司匹林预防性使用可降低子痫前期和小于胎龄儿的发生风险，但对胎盘早剥无显著影响。然而，对阿司匹林与治疗起始时的孕周和药物剂量关系的随机对照试验进行的荟萃分析表明，仅当治疗起始于≤16 孕周且药物日剂量≥100mg 时，才能显著降低子痫前期和小于胎龄儿的发生风险。
我们旨在评估阿司匹林与治疗起始时的孕周和药物剂量之间的胎盘早剥或产前出血风险的关系。
为了对评价妊娠期预防性使用阿司匹林的随机对照试验进行系统评价和荟萃分析，我们检索了 1985 年至 2017 年 9 月期间的 PubMed、Cinhal、Embase、Web of Science 和 Cochrane 图书馆。采用随机效应模型计算胎盘早剥或产前出血的相对风险及其 95%置信区间。根据阿司匹林的日剂量（<100mg 和≥100mg）和治疗起始时的孕周（≤16 周和>16 周）进行分层分析，并采用亚组差异分析进行比较。
共有 20 项研究，总计 12585 名参与者符合纳入标准。阿司匹林日剂量<100mg 对胎盘早剥或产前出血的风险无影响，无论起始治疗是在≤16 孕周（相对风险 1.11，95%置信区间 0.52-2.36）还是在>16 孕周（相对风险 1.32，95%置信区间 0.73-2.39）。阿司匹林日剂量≥100mg 时，无论起始治疗是在≤16 孕周（相对风险 0.62，95%置信区间 0.31-1.26）还是在>16 孕周（相对风险 2.08，95%置信区间 0.86-5.06），均与胎盘早剥或产前出血风险无显著变化，但亚组间差异有统计学意义（P=0.04）。
对于起始治疗于≤16 孕周的子痫前期预防，阿司匹林的日剂量≥100mg 可能会降低胎盘早剥或产前出血的风险，而不是起始治疗于>16 孕周。
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