Aspirin or anticoagulants for treating recurrent miscarriage in women without antiphospholipid syndrome

Kaandorp S, Di Nisio M, Goddijn M, Middeldorp S

Published Online:

January 21, 2009

Two studies (189 women) were included in the review. There is Insufficient evidence to say if anticoagulants help women with recurrent miscarriage without antiphospholipid syndrome.

Recurrent miscarriage (RM) is associated with inherited blood clotting disorders that could interfere with the placental blood circulation. Anticoagulant drugs for women with RM and such an underlying blood clotting problem may help, although these drugs may also cause excessive bleeding. Judgement if anticoagulants help women with RM in the absence of antiphospholipid syndrome is not possible because of the lack of sufficient evidence from the reviewed trials on this subject.

Abstract (click to read)

Background:

Since hypercoagulability might result in recurrent miscarriage, anticoagulant agents could potentially increase the live-birth rate in subsequent pregnancies in women with either inherited thrombophilia or unexplained recurrent miscarriage.

Objectives:

To evaluate the efficacy and safety of anticoagulant agents, such as aspirin and heparin, in women with a history of at least two miscarriages without apparent causes other than inherited thrombophilia.

Search strategy:

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2007, Issue 1), MEDLINE (January 1966 to March 2007), and EMBASE (1980 to March 2007). We scanned bibliographies of all located articles for any unidentified articles.

Selection criteria:

Randomised and quasi-randomised controlled trials that assessed the effect of anticoagulant treatment on the live-birth rate in women with a history of at least two miscarriages (up to 20 weeks of amenorrhoea) without apparent causes other than inherited thrombophilia were eligible. Interventions included aspirin, unfractionated heparin, and low molecular weight heparin for the prevention of miscarriage. One treatment could be compared with another or with placebo.

Data collection and analysis:

Two authors assessed the trials for inclusion in the review and extracted the data. We double checked the data.

Main results:

Two studies (189 participants) were included in the review. In one study, 54 pregnant women with recurrent miscarriage (RM) but no detectable anticardiolipin antibodies were randomised to low-dose aspirin or placebo. RM was defined as three or more consecutive miscarriages (occurring before 22 weeks' gestational age (based on last menstrual period)). Similar live-birth rates were observed with aspirin and placebo, both 81% (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.78 to 1.29). In the other study, 107 women with consecutive recurrent miscarriage without any apparent cause and no hereditary thrombophilia were randomised between enoxaparin and aspirin. Here RM was stated as three or more consecutive first trimester miscarriages or at least two consecutive second trimester miscarriages. Similar live birth rates were observed with enoxaparin and aspirin, respectively 82% and 84% (RR 0.97, 95% CI 0.81 to 1.16).

Authors' conclusions:

There is a paucity in studies on the efficacy and safety of aspirin and heparin in women with a history of at least two miscarriages without apparent causes other than inherited thrombophilia. The two reviewed trials studied different treatments and only one study was placebo-controlled. Neither of the studies showed a benefit of one treatment over the other. Therefore, the use of anticoagulants in this setting is not recommended. However, large randomised placebo-controlled trials are still urgently needed.

This record should be cited as:

Kaandorp S, Di Nisio M, Goddijn M, Middeldorp S. Aspirin or anticoagulants for treating recurrent miscarriage in women without antiphospholipid syndrome. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD004734. DOI: 10.1002/14651858.CD004734.pub3

Assessed as up to date:

April 30, 2008

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Primary Review Group:

Pregnancy and Childbirth Group

Health topics:

Pregnancy & childbirth > Miscarriage > Prevention

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Aspirin or anticoagulants for treating recurrent miscarriage in women without antiphospholipid syndrome

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