• factor V Leiden polymorphism;
  • miscarriage;
  • pregnancy loss;
  • prothrombin G20210A polymorphism

Summary.  Factor V Leiden (FVL) and prothrombin G20210A (FIIG20210A) mutations are associated with a higher risk of miscarriage: we sought to understand whether this association differs by clinical time of unexplained miscarriage, and by ethnic origin, among women with no previous thrombotic episode, during the first intended pregnancy. We performed a case–control study nested in a cohort of 32 683 women. We analyzed 3496 pairs of women matched for classical confounding factors. The FVL and FIIG20210A mutations were associated with an increased risk of miscarriage in Caucasian women [odds ratio (OR) 3.19, 95% confidence interval (CI) 2.37–4.30, P < 0.001 and OR 2.36, 95% CI, 1.72–3.24, P < 0.001, respectively]. Among non-Caucasian women, the mutations were rare and the associations with risk of miscarriage less clear. FVL and FIIG20210A mutations were independent risk factors for miscarriages only for women with related clinical signs occurring from the 10th week of gestation on (OR 3.46, 95% CI 2.53–4.72, P < 0.001 and OR 2.60, 95% CI 1.86–3.64, P < 0.001, respectively). These results indicate that FVL and FIIG20210A mutations are associated with a significant risk of spontaneous abortion which clinical signs occur from the 10th week on of the first intended pregnancy.