Summary

The conclusions of studies to date which evaluate a possibleassociation between factor V Leiden and adverse pregnancyoutcome have been conflicting. This study was undertaken tofurther investigate this association. Our objective was to evaluatethe association between adverse pregnancy outcomes andmaternal factor V Leiden genotype by meta-analysis. Inclusioncriteria were: (a) cohort or case control design; (b) outcomesclearly defined as one of the following: first or second/ third trimestermiscarriage or intrauterine death, preeclampsia, fetalgrowth retardation, or placental abruption; (c) both the caseand control mothers tested for the factor V Leiden mutation;(d) sufficient data for calculation of an odds ratio. Both fixedand random effect models were used to pool results and heterogeneityand publication bias were checked. For first trimesterfetal loss, the pooled odds ratio was heterogeneous(p=0.06) and no dose-response curve could be found. For second/third trimester fetal loss, there was a consistent and grad-edincrease in risk: the odds ratio was 2.4 (95% CI 1.1-5.2) forisolated (non-recurrent) third trimester fetal loss, rising to 10.7(95% CI 4.0-28.5) for those with 2 or more second/third trimesterfetal losses. Factor V Leiden is associated with a 2.9 fold(95% CI 2.0-4.3) increased risk of severe preeclampsia, and a4.8 fold (95% CI 2.4-9.4) increased risk of fetal growth retardation.These results support factor V Leiden testing for womenwith recurrent fetal loss in the second/third trimester. Womenwith only 1 event may also warrant testing if the fetal lossoccurred in the third trimester. Conversely, in those womenknown to have the factor V Leiden mutation, monitoring foradverse pregnancy outcomes is warranted; whether this meansincreased vigilance or anti-coagulant prophylaxis is still contentious.