Thrombophilic disorders and fetal loss: a meta-analysis

Background Our aim was to assess the strength of the controversial association between thrombophilia and fetal loss, and to examine whether it varies according to the timing or definition of fetal loss. Methods We searched Medline and Current Contents for articles published between 1975 and 2002 and their references with terms denoting recurrent fetal and nonrecurrent fetal loss combined with various thrombophilic disorders. We included in our meta-analysis case-control, cohort, and cross-sectional studies published in English, the methodological quality of which was rated as moderate or strong. Pooled odds ratios (OR) with 95% CI were generated by random effects models with Cochrane Review Manager software. Findings We included 31 studies. Factor V Leiden was associated with early (OR 2•01, 95% CI 1•13–3•58) and late (7•83, 2•83–21•67) recurrent fetal loss, and late nonrecurrent fetal loss (3•26, 1•82–5•83). Exclusion of women with other pathologies that could explain fetal loss strengthened the association between Factor V Leiden and recurrent fetal loss. Activated protein C resistance was associated with early recurrent fetal loss (3•48, 1•58–7•69), and prothrombin G20210A mutation with early recurrent (2•56, 1•04–6•29) and late non-recurrent (2•30, 1•09–4•87) fetal loss. Protein S deficiency was associated with recurrent fetal loss (14•72, 0•99–218•01) and late non-recurrent fetal loss (7•39, 1•28–42•63). Methylenetetrahydrofolate mutation, protein C, and antithrombin deficiencies were not significantly associated with fetal loss. Interpretation The magnitude of the association between thrombophilia and fetal loss varies, according to type of fetal loss and type of thrombophilia.