Inherited Thrombophilia and Preeclampsia Within a Multicenter Cohort: The Montreal Preeclampsia Study

Previous studies have suggested that inherited thrombophilia (hypercoagulability) may be associated with preeclampsia. Most of these studies were retrospective and showed positive associations between preeclampsia and several inherited thrombophilia polymorphisms. This prospective, multicenter case―control study investigated the association between inherited thrombophilia and preeclampsia among a cohort of 5337 pregnant women who were participants in the Montreal Preeclampsia Study, a large multicenter study of causal pathways of preterm birth. Of the 5165 woman followed up to delivery, 113 women (2.2%) developed preeclampsia and became the study group; 443 women who did not develop preeclampsia or nonproteinuric gestational hypertension became the control group. Prenatal blood samples were analyzed for the presence of 3 inherited thrombophilia polymorphisms (factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations), and homocysteine and folate levels were measured. The frequency of placental underperfusion (infarction, decidual vasculopathy, or syncytial knotting) was determined by pathological examination in all participants. Inherited thrombophilias were not more frequent in the study group than in the control group (14% vs. 21%, respectively); the adjusted odds ratio was 0.6, with a 95% confidence interval, of 0.3 to 1.3. Similar results were found for each individual thrombophilia, and were unchanged when the analysis was restricted to patients with early onset or severe preeclampsia. Homocysteine levels were higher in the control group than the study group. Placental underperfusion was found more frequently in the study group than in control group (63.2% vs. 46.2%, P < 0.0001) and among women with folate levels in the lowest quartile of control values (P = 0.04). There was no association, however, between placental underperfusion and thrombophilia either collectively or by individual mutation. These findings do not indicate an increased risk of preeclampsia among women with any of 3 inherited thrombophilias. The increase in placental underperfusion among women with preeclampsia seems to be associated with low plasma folate levels but not with the 3 thrombophilias examined.