Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant: Cochrane systematic review
Assessed as up to date: 2005/02/18
A range of treatments have been proposed to improve pregnancy outcome in recurrent pregnancy loss associated with antiphospholipid antibody (APL). Small studies have not resolved uncertainty about benefits and risks.Objectives
To examine outcomes of all treatments given to maintain pregnancy in women with prior miscarriage and APL.Search methods
We searched the Pregnancy and Childbirth Group's Trials Register (30 May 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2003, Issue 2), MEDLINE (1966 to June 2003), EMBASE (1988 to June 2003), handsearched Lupus (volume one to eight, 1991 to 1999) and conference proceedings from the International Symposium on APL up to 1999. We also scanned bibliographies of all located articles and contacted experts in the field.
We updated the search of the Pregnancy and Childbirth Group's Trials Register on 10 September 2009 and added the results to the awaiting classification section.Selection criteria
Randomised or quasi-randomised, controlled trials of interventions in pregnant women with a history of pregnancy loss and APL.Data collection and analysis
Two review authors independently assessed quality and extracted data for studies up to December 1999. One review author performed this for studies after 1999.Main results
Thirteen studies were found (849 participants). The quality was not high; 50% had clear evidence of allocation concealment. Participant characteristics varied between trials.
Unfractionated heparin combined with aspirin (two trials; n = 140) significantly reduced pregnancy loss compared to aspirin alone (relative risk (RR) 0.46, 95% confidence interval (CI) 0.29 to 0.71). Low molecular weight heparin (LMWH) combined with aspirin compared to aspirin (one trial; n = 98) did not significantly reduce pregnancy loss (RR 0.78, 95% CI 0.39 to 1.57). There was no advantage in high-dose, over low-dose, unfractionated heparin (one trial; n = 50). Three trials of aspirin alone (n = 135) showed no significant reduction in pregnancy loss (RR 1.05, 95% CI 0.66 to 1.68). Prednisone and aspirin (three trials; n = 286) resulted in a significant increase in prematurity when compared to placebo, aspirin, and heparin combined with aspirin, and an increase in gestational diabetes, but no significant benefit. Intravenous immunoglobulin +/- unfractionated heparin and aspirin (two trials; n = 58) was associated with an increased risk of pregnancy loss or premature birth when compared to unfractionated heparin or LMWH combined with aspirin (RR 2.51, 95% CI 1.27 to 4.95). When compared to prednisone and aspirin, intravenous immunoglobulin (one trial; n = 82) was not significantly different in outcomes.Authors' conclusions
Combined unfractionated heparin and aspirin may reduce pregnancy loss by 54%. Large, randomised controlled trials with adequate allocation concealment are needed to explore potential differences between unfractionated heparin and LMWH.
[Note: The 15 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]
Empson Marianne B, Lassere Marissa, Craig Jonathan C, Scott James R
Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant
Treatments for recurrent miscarriage when there are antibodies in the mothers blood.
Miscarriage can be very distressing for parents and their families. Miscarriage is sometimes associated with substances in the mother blood called 'antiphospholipid antibodies' or 'lupus anticoagulant'. These antibodies are associated with clotting and so it is suggested that anticlotting drugs may be helpful. The review found the quality of the included trials was quite variable, and that prednisone appears to have adverse effects so it has no role in the treatment of recurrent miscarriage. However, a combination of unfractionated heparin with aspirin may be helpful but there are potential side-effects for mothers. More research is needed.
Implications for practice
The combination of twice-daily unfractionated heparin and low-dose aspirin appears to be of benefit in pregnant women with antiphospholipid antibodies and recurrent pregnancy loss not related to other causes. The benefits in low-risk participants may not be sufficient to warrant its use. LMW may be of benefit but there is no evidence that it has similar efficacy to heparin and its use as a substitute for unfractionated heparin can not be justified based on present data. There is no evidence that other therapies may provide benefit but there is some evidence of harm with prednisone and intravenous immunoglobulin.
Implications for research
Further large trials of heparin (both unfractionated and LMW) combined with aspirin are needed to reduce clinically important uncertainty about the benefits and harms. A large multicentre study comparing unfractionated heparin and aspirin with LMW heparin and aspirin, and aspirin alone is well overdue. Until this is done, debate about the efficacy of LMW heparin, unfractionated heparin and their interchangability will continue.
[Note: The 15 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]Get full text at The Cochrane Library
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