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.
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.


RESULTS
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.
Rodger
Marc A
MA
Thrombosis Program, Division of Hematology, Departments of Medicine, Obstetrics and Gynecology and Epidemiology/Community Medicine, University of Ottawa, Ottawa, Ontario, Canada. mrodger@ohri.ca
Betancourt
Marisol T
MT
Clark
Peter
P
Lindqvist
Pelle G
PG
Dizon-Townson
Donna
D
Said
Joanne
J
Seligsohn
Uri
U
Carrier
Marc
M
Salomon
Ophira
O
Greer
Ian A
IA
D000022:Abortion, Spontaneous / Q000235:genetics*; D000037:Abruptio Placentae / Q000235:genetics; D005165:Factor V / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D009154:Mutation; D016017:Odds Ratio; D010920:Placenta; D011225:Pre-Eclampsia / Q000235:genetics; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000235:genetics*; D011516:Prothrombin / Q000235:genetics*; D012307:Risk Factors; D050497:Stillbirth / Q000235:genetics*; D019851:Thrombophilia / Q000235:genetics*
C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin