Background: Venous thrombosis is one of the leading causes of maternal morbidity and mortality. Objective: In the MEGA study, we evaluated pregnancy and the postpartum period as risk factors for venous thrombosis in 285 patients and 857 control subjects. Patients/methods: Between March 1999 and September 2004, consecutive patients with a first episode of venous thrombosis were included from six anticoagulation clinics. Partners of patients and a random digit dialing group were included as control subjects. Participants completed a questionnaire and DNA was collected. Results: The risk of venous thrombosis was 5‐fold (OR, 4.6; 95% CI, 2.7–7.8) increased during pregnancy and 60‐fold (OR, 60.1; 95% CI, 26.5–135.9) increased during the first 3 months after delivery compared with non‐pregnant women. A 14‐fold increased risk of deep venous thrombosis of the leg was found compared with a 6‐fold increased risk of pulmonary embolism. The risk was highest in the third trimester of pregnancy (OR, 8.8; 95% CI, 4.5–17.3) and during the first 6 weeks after delivery (OR, 84.0; 95% CI, 31.7–222.6). The risk of pregnancy‐associated venous thrombosis was 52‐fold increased in factor V Leiden carriers (OR, 52.2; 95% CI, 12.4–219.5) and 31‐fold increased in carriers of the prothrombin 20210A mutation (OR, 30.7; 95% CI, 4.6–203.6) compared with non‐pregnant women without the mutation. Conclusion: We found an increased risk of venous thrombosis during pregnancy and the postpartum period, with an especially high risk during the first 6 weeks postpartum. The risk of pregnancy‐associated venous thrombosis was highly increased in carriers of factor V Leiden or the prothrombin 20210A mutation.
