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Meta-Analysis
. 2010 Jun 15;7(6):e1000292.
doi: 10.1371/journal.pmed.1000292.

The association of factor V leiden and prothrombin gene mutation and placenta-mediated pregnancy complications: a systematic review and meta-analysis of prospective cohort studies

Marc A Rodger  1 , Marisol T Betancourt, Peter Clark, Pelle G Lindqvist, Donna Dizon-Townson, Joanne Said, Uri Seligsohn, Marc Carrier, Ophira Salomon, Ian A Greer
Affiliations
Meta-Analysis

The association of factor V leiden and prothrombin gene mutation and placenta-mediated pregnancy complications: a systematic review and meta-analysis of prospective cohort studies

Marc A Rodger et al. PLoS Med. .

Abstract

Background: Factor V Leiden (FVL) and prothrombin gene mutation (PGM) are common inherited thrombophilias. Retrospective studies variably suggest a link between maternal FVL/PGM and placenta-mediated pregnancy complications including pregnancy loss, small for gestational age, pre-eclampsia and placental abruption. Prospective cohort studies provide a superior methodologic design but require larger sample sizes to detect important effects. We undertook a systematic review and a meta-analysis of prospective cohort studies to estimate the association of maternal FVL or PGM carrier status and placenta-mediated pregnancy complications.

Methods and findings: A comprehensive search strategy was run in Medline and Embase. Inclusion criteria were: (1) prospective cohort design; (2) clearly defined outcomes including one of the following: pregnancy loss, small for gestational age, pre-eclampsia or placental abruption; (3) maternal FVL or PGM carrier status; (4) sufficient data for calculation of odds ratios (ORs). We identified 322 titles, reviewed 30 articles for inclusion and exclusion criteria, and included ten studies in the meta-analysis. The odds of pregnancy loss in women with FVL (absolute risk 4.2%) was 52% higher (OR = 1.52, 95% confidence interval [CI] 1.06-2.19) as compared with women without FVL (absolute risk 3.2%). There was no significant association between FVL and pre-eclampsia (OR = 1.23, 95% CI 0.89-1.70) or between FVL and SGA (OR = 1.0, 95% CI 0.80-1.25). PGM was not associated with pre-eclampsia (OR = 1.25, 95% CI 0.79-1.99) or SGA (OR 1.25, 95% CI 0.92-1.70).

Conclusions: Women with FVL appear to be at a small absolute increased risk of late pregnancy loss. Women with FVL and PGM appear not to be at increased risk of pre-eclampsia or birth of SGA infants. Please see later in the article for the Editors' Summary.

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Conflict of interest statement

MAR is the principal investigator of a Canadian Institutes of Health Research randomised trial comparing dalteparin to no dalteparin to prevent placenta-mediated pregnancy complications in thrombophilic women. MAR has received grant funding from Pfizer, Sanofi, Boehringer Ingelheim, Bayer, GTC Therapeutics, and Leo Pharma. MAR has also served on advisory boards for Boehringer Ingelheim and Biomerieux but not been paid. IAG has received Honoraria for lectures and advisory boards from Sanofi Aventis and Leo Pharma.

Figures

Figure 1
Figure 1. Study selection.
Figure 2
Figure 2. Odds of placenta-mediated pregnancy complications in FVL (homozygous or heterozygous)-positive women.
Figure 3
Figure 3. Odds of placenta-mediated pregnancy complications in PGM (homozygous or heterozygous)-positive women.
Figure 4
Figure 4. FVL and composite placenta-mediated pregnancy complications.
Figure 5
Figure 5. PGM and composite placenta-mediated pregnancy complications.
See this image and copyright information in PMC

References

    1. Brenner B. Antithrombotic prophylaxis for women with thrombophilia and pregnancy complications - Yes. J Thromb Haemost. 2003;1:2070. - PubMed
    1. Brenner B. Thrombophilia and adverse pregnancy outcome. Obstet Gynecol Clin North Am. 2006;33:ix. - PubMed
    1. Rodger MA, Paidas M, McLintock C, Middeldorp S, Kahn S, et al. Inherited thrombophilia and pregnancy complications revisited. Obstet Gynecol. 2008;112:320. - PubMed
    1. Kujovich JL. Thrombophilia and pregnancy complications. Am J Obstet Gynecol. 2004;191:412. - PubMed
    1. Brown K, Luddington R, Williamson D, Baker P, Baglin T. Risk of venous thromboembolism associated with a G to A transition at position 20210 in the 3′-untranslated region of the prothrombin gene. Br J Haematol. 1997;98:907. - PubMed