in pregnant women with mechanical heart valves , the frequency of valve thrombosis increases due to pregnancy - related hypercoagulability . therefore , effective anticoagulation is critical in pregnant patients with mechanical heart valves but remains problematic because both oral anticoagulation and heparins have been associated with important fetal and maternal side effects ( 1 ) . coumarin derivatives are anticoagulants of choice for mechanical heart valves , but they cross the placenta and are associated with coumarin - induced fetal loss or embryopathy ( 1 - 3 ) . unfractionated heparin ( ufh ) provides an alternative therapy that avoids fetal side effects , however , the use of ufh is associated with increased maternal thromboembolic and bleeding complications ( 1 , 4 , 5 ) . low molecular weight heparin ( lmwh ) may be more advantageous than ufh ( 6 ) , and appears a good alternative . however , little clinical information and no reliable data are available regarding its efficacy and safety . no consensus has been reached about optimal antithrombotic therapy in pregnant patients with a mechanical heart valve . coumarins are contraindicated in pregnancy in north america due to fetal concerns , but european experts have recommended low dose coumarins ( less than 5 mg daily ) throughout pregnancy given a very low frequency of fetal anomalies ( 2 , 3 ) . reports of lmwh use began to appear , and many physicians now use lmwh because of its good safety profile for both mother and baby ( 7 - 10 ) . however , treatment failures have been reported ( 11 , 12 ) , and no lmwh has been licensed for use in pregnant patients with mechanical heart valves . available published data regarding the efficacy and safety of lmwh in this clinical setting have been derived from small case series , and usually enoxaparin has been used . here , we report our experience of nadroparin treatment , and its associated pregnancy outcomes and maternal complications . between 1997 and 2005 , 31 pregnancies were analyzed retrospectively in 25 women with mechanical heart valves . basic characteristics and previous operative data are listed in table 1 . in 23 of these 31 pregnancies , nadroparin was used as an anticoagulant during the first trimester with given informed consent , concerning the risks and benefits of lmwh . others were anticoagulated with coumarin derivatives ( cmd ) with or without aspirin due to unawareness of pregnancy until the first trimester , or because of refusal or poor compliance on self - injected lmwh . in the lmwh - treated group , when pregnancy was confirmed , coumarins were stopped and changed to subcutaneous nadroparin ( 7,500 u , twice daily ) , from 6 weeks to 12 weeks of gestation . aspirin , at 100 mg / day , was also administrated throughout the pregnancy . at gestation week 38 , women were scheduled for labor induction and changed to nadroparin to avoid the delivery of an anticoagulated fetus . after establishing labor , we carefully checked for hemorrhages and other complications , and babies were examined for congenital anomalies and weight . in the cmd - treated group , coumarins and aspirin were continued throughout the pregnancy and the target international normalized ratio ( inr ) was maintained between 2.5 to 3.5 . coumarins were changed to nadroparin before 2 weeks prior to the expected delivery date to avoid fetal bleeding complications during delivery . pregnancy outcomes , namely , numbers of healthy babies , fetal anomalies , fetal losses , and maternal complications , including thromboembolism or bleeding , were analyzed . to evaluate the efficacy and safety of lmwh , eight pregnancies , maintained using coumarins throughout pregnancy , were compared . data were analyzed using spss for windows version 10.0 software and compared using the student 's t - test , at a level of significance of p<0.05 . no maternal death or bleeding complication occurred in either the lmwh - treated group or the cmd - treated group . frequencies of maternal thromboembolism were not different between the two groups ( table 2 ) . a maternal transient ischemic attack ( tia ) occurred in one case in each group , and both patients had previously undergone mitral valve replacement . prosthetic mitral valve thrombosis occurred in three pregnancies , two in the lmwh group and one in the cmd group ( table 3 ) . the two of these three patients underwent redo surgery , and other patient was managed on thrombolytic therapy . numbers of live born and healthy babies were higher in the lmwh group ( table 4 ) . in both groups , two babies had low birth weights of 2.1 kg and 2.4 kg , but were otherwise healthy . in the cmd group , one baby had hydrocephalus . however , the frequency of fetal loss including therapeutic abortion and stillbirth were significantly higher in the cmd group . two fetal losses occurred in the lmwh group , both occurred in cases of maternal valve thrombosis . four fetal losses occurred in the cmd group , and one of these involved maternal valve thrombosis . this study demonstrates that lmwh - based therapy is superior to coumarin therapy in pregnant women with a prosthetic heart valve , and that the use of nadroparin during the first trimester with 100 mg of aspirin throughout pregnancy could be a safe and effective protocol for thromboprophylaxis in these women . recent recommendations , published in 2004 as part of the 7th american college of chest physicians ( accp ) consensus on antithrombotic therapy ( 12 ) , included the following three regimens : 1 ) aggressive adjusted - dose lmwh throughout pregnancy ; 2 ) adjusted - dose ufh , throughout pregnancy ; or 3 ) either lmwh or ufh between 6 and 12 weeks and close - to - term only and the use of cmd at other times . our protocol was similar to the third regimen , but we also administered aspirin ( 100 mg daily ) throughout pregnancy to reduce coumarin dosages and the risk of thromboembolism . the overall frequencies of maternal thromboembolism , including valve thrombosis , were similar in both groups , but the frequencies of live and healthy baby births were higher in the lmwh group . these results demonstrate that lmwh - based therapy is a good alternative to coumarins , because it has similar anticoagulation effects with lower fetal side effects . exposure to coumarins during the second part of the first trimester is associated with fetal loss , primarily due to spontaneous abortion or coumarin - induced embryopathy . the reported frequencies of coumarins - related embryopathy vary for debatable reasons ( 14 , 15 ) , a recent study suggested that coumarin risk is dose related and that adverse effects occur mainly in women taking > 5 mg daily . , the target inr was maintained with less than 5 mg of coumarins in all patients in the cmd group ; however , a half of these lost their babies due to abortion or stillbirth . our results represent only observational data , and the effect of dose - related embryopathy remains uncertain . lmwh does not cross the placental barrier and offers potential advantages compared with ufh in terms of better safety profile with less thrombocytopenia , less bleeding , less osteoporosis with prolonged treatment , a more predictable and rapidly reached anticoagulant effect , and the possibility of self - administration of anticoagulant therapy without laboratory monitoring . however , treatment failures have been reported , and the use of lmwh for pregnant women with mechanical heart valves has become controversial due to small numbers of patients and a lack of accurate postmarketing data ( 16 ) . a recent review of 81 pregnancies in 75 women treated with lmwh reported an 8.6% rate of valve thrombosis ( 17 ) , and found that appropriate dose adjustments could reduce the frequency of thromboembolism . the 7th accp recommendations call for the use of lmwh at levels that achieve peak anti - factor xa values of around 1.0 u / ml ( 12 ) . a recent prospective study with deltaparin reported that dosages based on body weight were inadequate to maintain a therapeutic level of lmwh in pregnancy ( 18 ) . our data demonstrate that valve thrombosis occurred in 2 patients treated with nadroparin ; a prevalence of 8.7% . unfortunately , we did not monitor anti - xa levels during nadroparin administration , and thus , we can not conclude that valve thrombosis is associated with an inadequate nadroparin dose . further studies , with sufficient statistical power , are required to clarify the clinical significance of anti - xa levels . in conclusion , despite the retrospective design of the present study , it might be worth to mention that lmwh appears a safe and effective substitute for any other anticoagulants in pregnant women with mechanical heart valves . we have experienced that pregnancy outcomes are acceptable with lmwh , but that its efficacy for preventing valve thrombosis remains uncertain . further studies are needed in order to establish appropriate management protocols for pregnant women with mechanical heart valves .
no definitive recommendation is available concerning optimal antithrombotic therapy in pregnant women with a mechanical heart valve . the purpose of the current study was to evaluate the clinical results of nadroparin treatment with respect to pregnancy outcome and maternal complications . from 1997 to 2005 , 31 pregnancies were reviewed in 25 women . 
 nadroparin ( 7,500 u , twice daily ) was used in 23 pregnancies between 6 and 12 weeks of gestation and close - to - term only , and coumarin derivatives were used with aspirin at other times . 
 eight pregnant women treated with coumarin derivatives throughout pregnancy were compared to evaluate the safety and efficacy of nadroparin . 
 no maternal death or bleeding complication occurred in either of the two groups , and frequencies of maternal thromboembolism including valve thrombosis ( 8.7% vs. 12.5% , p>0.05 ) were similar . 
 however , the frequencies of live born ( 91.3% vs. 50% , p=0.01 ) and healthy babies ( 90.4% vs. 25% , p<0.01 ) were significantly higher , and the fetal loss rate was significantly lower ( 8.7% vs. 50% , p=0.01 ) in the nadroparin - treated group . regarding the efficacy and safety of antithrombotic treatment in pregnant women with prosthetic heart valves , nadroparin treatment during the first trimester is an acceptable regimen and produces better results than coumarin derivatives .