Is thrombophilia associated with placenta-mediated pregnancy complications? A prospective cohort study.
BACKGROUND
Case control studies suggest that genetic thrombophilias increase the risk of placenta-mediated pregnancy complications (pregnancy loss, small for gestational age (SGA), preeclampsia and/or placental abruption). Cohort studies have not supported this association but were underpowered to detect small effects.


OBJECTIVE
To determine if factor V Leiden (FVL) or the prothrombin gene mutation (PGM) were associated with placenta-mediated pregnancy complications.


METHODS
A prospective cohort of unselected, consenting pregnant women at three Canadian tertiary care hospitals had blood drawn in the early second trimester and were genotyped for FVL and PGM after delivery. The main outcome measure was a composite of pregnancy loss, SGA < 10th percentile, preeclampsia or placental abruption.


RESULTS
Complete primary outcome and genetic data were available for 7343 women. Most were Caucasian (77.7%, n = 5707), mean age was 30.4 (± 5.1) years, and half were nulliparous. There were 507 (6.9%) women with FVL and/or PGM; 11.64% had a placenta-mediated pregnancy complication. Of the remaining 6836 women, 11.23% experienced a complication. FVL and/or PGM was associated with a relative risk of 1.04 (95% CI, 0.81-1.33) for the composite outcome, with similar results after adjustment for important covariates.


CONCLUSIONS
Carriers of FVL or PGM are not at significantly increased risk of these pregnancy complications.
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Division of Hematology, The Ottawa Hospital, Ottawa, ON, Canada; Department of Medicine, The University of Ottawa, Ottawa, ON, Canada.
M A
MA
Rodger
M C
MC
Walker
G N
GN
Smith
P S
PS
Wells
T
T
Ramsay
N J
NJ
Langlois
N
N
Carson
M
M
Carrier
R
R
Rennicks White
S
S
Shachkina
S W
SW
Wen
D000328:Adult; D005165:Factor V / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D009154:Mutation; D010920:Placenta / Q000503:physiopathology*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000175:diagnosis*; D011446:Prospective Studies; D011516:Prothrombin / Q000235:genetics*; D012307:Risk Factors; D019851:Thrombophilia / Q000150:complications* / Q000235:genetics; D016896:Treatment Outcome
C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin
cohort study; genetics; meta-analysis; pregnancy; risk factors