INCREASED FETAL LOSS IN WOMEN WITH HERITABLE THROMBOPHILIA

Background A successful outcome of pregnancy requires an efficient ute roplacental vascular system. Since this system may be compromised by d isorders of haemostasis associated with a prothrombotic state, we post ulated that maternal thrombophilia might be a risk factor for fetal lo ss, We studied the relation between heritable thrombophilic defects an d fetal loss in a cohort of women with factor V Leiden or deficiency o f antithrombin, protein C, or protein S. Methods We studied 1384 women enrolled in the European Prospective Cohort on Thrombophilia (EPCOT). Of 843 women with thrombophilia 571 had 1524 pregnancies; of 541 cont rol women 395 had 1019 pregnancies. The controls were partners of male members of the EPCOT cohort or acquaintances of cases. We analysed th e frequencies of miscarriage (fetal loss at or before 28 weeks of gest ation) and stillbirth (fetal loss after 28 weeks of gestation) jointly and separately. Findings The risk of fetal loss was increased in wome n with thrombophilia (168/571 vs 93/395; odds ratio 1.35 [95% CI 1.01- 1.82]). The odds ratio was higher for stillbirth than for miscarriage (3.6 [1.4-9.4] vs 1.27 [0.94-1.71]). The highest odds ratio for stillb irth was in women with combined defects (14.3 [2.4-86.0]) compared wit h 5.2 (1.5-18.1) in antithrombin deficiency, 2.3 (0.6-8.3) in protein- C deficiency, 3.3 (1.0-11.3) in protein-S deficiency, and 2.0 (0.5-7.7 ) with factor V Leiden. The corresponding odds ratios for miscarriage in these subgroups were 0.8 (0.2-3.6), 1.7 (1.0-2.8), 1.4 (0.9-2.2), 1 .2 (0.7-1.9), and 0.9 (0.5-1.5). Significantly more pregnancy terminat ions had been done in women with thrombophilia than in controls (odds ratio 2.9 [1.8-4.8]); this discrepancy was apparent in nine of 11 part icipating centres and for all thrombophilia subgroups. Interpretation Women with familial thrombophilia, especially those with combined defe cts or antithrombin deficiency, have an increased risk of fetal loss, particularly stillbirth. Our findings have important implications for therapy and provide a rationale for clinical trials of thromboprophyla xis for affected women with recurrent fetal loss.