Hereditary thrombophilia as a cause of fetal loss

Abstract

Objective: Hypercoagulability, leading to uteroplacental thrombosis, has been implicated in pregnancy loss. Recently, three genetic mutations causing hypercoagulability have been described: Factor V Leiden, Prothrombin 20210A, and Methylenetetrahydrofolate reductase A223V. The purpose of this study is to determine the risk of these mutations in women with a history of pregnancy loss versus a control population with no antecedent fetal loss.Methods: A prospective cohort study compared 67 women 20–46 years of age with a history of 1–11 first-trimester pregnancy losses and 43 females in the control group 22–73 years of age with 1–5 successful pregnancies and no history of first-trimester pregnancy loss. Two-by-two table analyses with relative risk and 95% confidence intervals were calculated.Results: The mutations of Factor V Leiden and Prothrombin 20210A were not found to be statistically different between the study group and control group. The chance of the Methylenetetrahydrofolate reductase A223V mutation was statistically higher in the subject group with a relative risk of 2.4 (C.I. 1.45–4.00). Both the homozygous and heterozygous mutations were higher in the study group versus the control group.Conclusions: The presence of Methylenetetrahydrofolate reductase mutation is higher in women with a history of first-trimester pregnancy losses as compared with the control population with no history of first-trimester loss. This was not seen with mutations of Factor V Leiden or Prothrombin 20210A. Further studies must be performed to determine the presence of these mutations in women with recurrent pregnancy losses. Other known risk factors including antiphospholipid syndrome and other hypercoagulable conditions also should be concurrently analyzed. A confounding or possible synergistic effect between multiple conditions may exist in women with recurrent losses.