Journal Article

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

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

2010

Overview

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. 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). 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Abortion, Spontaneous - genetics / Abruptio Placentae - genetics / Factor V - genetics / Female / Hematology / Hematology/Coagulation Disorders / Humans / Infant, Newborn / Infant, Small for Gestational Age / Medical research / Miscarriage / Mutation / Obstetrics/Pregnancy / Odds Ratio / Placenta / Pre-Eclampsia - genetics / Pregnancy / Pregnancy Complications, Hematologic - genetics / Prothrombin - genetics / Risk Factors / Stillbirth - genetics / Studies / Thrombophilia - genetics