Anticoagulation of pregnant women with mechanical heart valves - A systematic review of the literature

Background: The management of women with prosthetic heart valves during pre gnancy poses a particular challenge as there are no available controlled cl inical trials to provide guidelines for effective antithrombotic therapy. O ral anticoagulants such as warfarin sodium cause fetal embryopathy; subcuta neous administration of heparin sodium has been reported to be ineffective in preventing thromboembolic complications. Objective: To identify the risks of maternal and fetal complications in wom en with mechanical heart valves treated with different anticoagulation regi mens during pregnancy. Methods: We performed a systematic review of the literature to determine po oled estimates of maternal and fetal risks associated with the 3 commonly u sed approaches: (1) oral anticoagulants (OA) throughout pregnancy, (2) repl acing OA with heparin in the first trimester (from 6-12 weeks' gestation), and (3) heparin use throughout pregnancy. Fetal outcomes included spontaneo us abortions and fetopathic effects, and maternal outcomes were major bleed ing, thromboembolic complications, and death. Results: The use of OA throughout pregnancy is associated with warfarin emb ryopathy in 6.4%;, (95% confidence interval [CI], 4.6%-8.9%) of livebirths. The substitution of heparin at or prior to 6 weeks, and continued until 12 weeks, eliminated this risk. Overall risks for fetal wastage (spontaneous abortion, stillbirths, and neonatal deaths) were similar in women treated w ith OA throughout, compared with women treated with heparin in the first tr imester. Maternal mortality was 2.9% (95% CI, 1.9%-4.2%). Major bleeding ev ents occurred in 2.5% (95% CI, 1.7%-3.5%) of all pregnancies, most at the t ime of delivery. The regimen associated with the lowest risk of valve throm bosis (3.9%; 95% CI, 2.9-5.9%) was the use of OA throughout; using heparin only between 6 and 12 weeks' gestation was associated with an increased ris k of valve thrombosis (9.2%; 95% CI, 5.9%-13.9%). Conclusions: Thromboembolic prophylaxis of women with mechanical heart valv es during pregnancy is best achieved with OA; however, this increases the r isk of fetal embryopathy. Substituting OA with heparin between 6 and 12 wee ks reduces the risk of fetopathic effects, but with an increased risk of th romboembolic complications. The use of low-dose heparin is definitely inade quate; the use of adjusted-dose heparin warrants aggressive monitoring and appropriate dose adjustment. Large prospective trials to determine the best regimen for these women are needed.