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Data about associations between inherited thrombophilias and adverse pregnancy outcomes are inconsistent. Researchers conducted a prospective cohort study to evaluate pregnancy outcomes in 1700 nulliparous women who underwent genotyping before 22 weeks' gestation for factor V Leiden, prothrombin gene mutations, methylenetetrahydrofolate reductase enzyme (MTHFR) mutations, and thrombomodulin polymorphisms. Women were asymptomatic and had no family or personal histories of thromboembolism or thrombophilia; healthcare providers were blinded to the women's thrombophilia status. Pregnancies were followed for a primary composite outcome of severe preeclampsia, fetal growth restriction, stillbirth, placental abruption, or neonatal death.
Among carriers of inherited thrombophilias, risks for adverse pregnancy outcomes of interest (which occurred in 8% of participants overall) were similar to those in noncarriers. Women who carried the thrombin gene mutation were at excess risk for the primary outcome (adjusted odds ratio, 3.58; P=0.02); by contrast, homozygosity for the MTHFR A1298C polymorphism (seen in almost 10% of the cohort) conferred a protective effect (aOR, 0.44; P=0.03). Factor V Leiden was associated with excess risk for stillbirth, and prothrombin gene mutation was associated with excess risk for placental abruption, but both associations had wide confidence intervals.
Said JM et al. Inherited thrombophilia polymorphisms and pregnancy outcomes in nulliparous women. Obstet Gynecol 2010 Jan; 115:5.
Branch DW. The truth about inherited thrombophilias and pregnancy. Obstet Gynecol 2010 Jan; 115:2.
Comment
As the authors note, relying on composite outcomes increases the chances of obtaining statistically significant results; therefore, the few significant associations observed in this study might not be clinically relevant. In an accompanying editorial, Dr. Ware Branch theorizes that our enthusiasm for treating pregnant women who have thrombophilias stems from the apparent successes of anticoagulant treatment for women with antiphospholipid syndrome (although results of two prospective trials showed that treating such women with heparin did not improve live birth rates). For me, sorting through the literature and separating inherited thrombophilias from antiphospholipid syndrome has been problematic. One new finding that has helped me to distinguish among these disorders is that adverse pregnancy outcomes that are associated with antiphospholipid syndrome arise primarily from inflammation, not thrombosis. To elucidate these issues further, we need large, well-designed studies on thrombophilia treatments and adverse pregnancy outcomes. Until such studies are conducted, routine anticoagulant treatment during all pregnancies is not appropriate for women with thrombophilias.