D'Souza Rohan, Ostro Jackie, Shah Prakesh S, Silversides Candice K, Malinowski Ann, Murphy Kellie E, Sermer Mathew, Shehata Nadine
Department of Obstetrics and Gynaecology, Division of Maternal and Fetal Medicine, Mount Sinai Hospital, University of Toronto, 700 University Avenue, Toronto ON M5G 1Z5, Canada.
Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Toronto ON M5T 3M6, Canada.
Eur Heart J. 2017 May 14;38(19):1509-1516. doi: 10.1093/eurheartj/ehx032.
To review maternal and foetal outcomes in women with mechanical heart valves (MHVs) treated with vitamin-K antagonists (VKAs), first-trimester heparin followed by VKAs (sequential treatment), low molecular weight heparin (LMWH) and unfractionated heparin (UFH) during pregnancy, in order to inform practice.
Medline, Embase and Central were searched from inception until February 2016. Two reviewers independently screened 1786 titles, reviewed 110 full-texts and extracted data and assessed risk-of-bias from 46 articles. Pooled incidence (95% confidence intervals) was calculated for maternal and foetal outcomes. Included studies had a moderate or high risk-of-bias. With VKAs, sequential treatment and LMWH, maternal mortality occurred in 0.9% (0.4-1.4), 2.0% (0.8-3.1) and 2.9% (0.2-5.7), thromboembolic complications in 2.7% (1.4-4.0), 5.8% (3.8-7.7) and 8.7% (3.9-13.4), livebirths in 64.5% (48.8-80.2), 79.9% (74.3-85.6) and 92.0% (86.1-98.0) and anticoagulant-related foetal/neonatal adverse events (embryopathy or foetopathy) in 2.0% (0.3-3.7), 1.4% (0.3-2.5) and 0%, respectively. When UFH is used throughout pregnancy, 11.2% (2.8-19.6) suffered thromboembolic complications. Foetal loss and adverse events occurred with first-trimester warfarin doses ≤ 5 mg/day, although there were more livebirths [83.6% (75.8-91.4) vs. 43.9% (32.8-55.0)] and fewer foetal anomalies [2.3% (0.7-4.0) vs. 12.4% (3.3-21.6)] with lower doses than with warfarin > 5 mg/day.
VKAs are associated with fewest maternal complications but also with fewest livebirths. Sequential treatment does not eliminate anticoagulant-related foetal/neonatal adverse events. LMWH is associated with the highest number of livebirths. The safety of UFH throughout pregnancy and first-trimester warfarin ≤ 5 mg/day remains unconfirmed.
回顾在孕期使用维生素K拮抗剂（VKA）、孕早期使用肝素随后使用VKA（序贯治疗）、低分子量肝素（LMWH）和普通肝素（UFH）治疗的机械心脏瓣膜（MHV）女性的母婴结局，以为临床实践提供参考。
检索Medline、Embase和Central数据库，时间跨度从建库至2016年2月。两名研究者独立筛选了1786篇标题，审阅了110篇全文，并从46篇文章中提取数据并评估偏倚风险。计算了母婴结局的合并发生率（95%置信区间）。纳入的研究存在中度或高度偏倚风险。使用VKA、序贯治疗和LMWH时，孕产妇死亡率分别为0.9%（0.4 - 1.4）、2.0%（0.8 - 3.1）和2.9%（0.2 - 5.7），血栓栓塞并发症发生率分别为2.7%（1.4 - 4.0）、5.8%（3.8 - 7.7）和8.7%（3.9 - 13.4），活产率分别为64.5%（48.8 - 80.2）、79.9%（74.3 - 85.6）和92.0%（86.1 - 98.0），抗凝相关的胎儿/新生儿不良事件（胚胎病或胎儿病）发生率分别为2.0%（0.3 - 3.7）、1.4%（0.3 - 2.5）和0%。在整个孕期使用UFH时，11.2%（2.8 - 19.6）发生血栓栓塞并发症。孕早期华法林剂量≤5mg/天时会出现胎儿丢失和不良事件，尽管与华法林剂量>5mg/天相比，较低剂量时活产率更高[83.6%（75.8 - 91.4）对43.9%（32.8 - 55.0）]，胎儿畸形更少[2.3%（0.7 - 4.0）对12.4%（3.3 - 21.6）]。
VKA与最少的孕产妇并发症相关，但活产数也最少。序贯治疗不能消除抗凝相关的胎儿/新生儿不良事件。LMWH与最高的活产数相关。整个孕期使用UFH以及孕早期使用≤5mg/天的华法林的安全性尚未得到证实。
