It's important to understand that most positive associations between inherited thrombophilias and adverse pregnancy outcomes were derived from small case-control studies subject to selection and ascertainment biases.
Prior case-control studies had implicated thrombophilias in recurrent fetal loss. In 1996, a case-control study nested in the European Prospective Cohort on Thrombophilia (EPCOT) compared 571 women with thrombophilia with 395 control patients and reported an increased risk of fetal loss (miscarriage and stillbirth) among the former patients (29.4% vs 23.5%; P=.04).2 The risk of loss was greater after 28 weeks than at or before 28 weeks (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.4-9.4] vs OR, 1.27; 95% CI, 0.94-1.71). The highest risk for stillbirth was observed in women with combined thrombophilic defects and antithrombin and protein C deficiencies. A 1998 study found a prevalence of FVL in 8.0% of consecutively tested recurrent aborters vs 3.7% of parous controls (OR, 2.3; 95% CI, 1.0-5.2).3 In a meta-analysis of 31 studies, FVL was associated with first-trimester pregnancy loss (OR, 2.01; 95% CI, 1.13-3.58) but more strongly with late (>19 weeks) nonrecurrent fetal loss (OR, 3.26; 95% CI, 1.82-5.83).4 In 2005, another case-control study nested in the 32,700 Nimes Obstetricians and Haematologists (NOHA) cohort reported an association between FVL and pregnancy loss after 10 weeks (OR, 3.46; 95% CI, 2.53-4.72) but not for losses between 3 and 9 weeks.5 However, although these studies suggested a link between FVL, and perhaps other thrombophilias, and stillbirth, the absolute magnitude of the association was modest. A 3-fold increase of a rare event is still a rare event.