FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 343:1015-1018 October 5, 2000 Number 14 Next

	Full Text PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background The Factor V Leiden and prothrombin-gene mutations are independent risk factors for venous thrombosis; it is debated whether a mutation in the gene encoding methylenetetrahydrofolate reductase, an enzyme involved in homocysteine metabolism, also increases the risk of venous thrombosis. Whether any of these mutations is associated with an increased risk of late fetal death is not known.

Methods We studied 67 women with a first episode of unexplained late fetal loss (fetal death after 20 weeks or more of gestation) and 232 women who had had one or more normal pregnancies and no late fetal losses. All the women were tested for the presence of three gene mutations. Women with other thrombophilic conditions were excluded from the study.

Results Eleven of the 67 women with late fetal loss (16 percent) and 13 of the 232 control women (6 percent) had either the factor V or the prothrombin mutation. The relative risks of late fetal loss in carriers of the factor V and prothrombin mutations were 3.2 (95 percent confidence interval, 1.0 to 10.9) and 3.3 (95 percent confidence interval, 1.1 to 10.3), respectively. Thirteen percent of the women whose fetuses died and 20 percent of the control women were homozygous for the mutation in the methylenetetrahydrofolate reductase gene (relative risk, 0.8; 95 percent confidence interval, 0.5 to 1.2).

Conclusions Both the factor V and the prothrombin mutations are associated with an approximate tripling of the risk of late fetal loss.

Source Information

From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center (I.M., A.M., S.G., P.M.M.) and the Epidemiology Unit (E.T.), Istituto di Ricovero e Cura a Carattere Scientifico Maggiore Hospital, the Department of Obstetrics and Gynecology, San Paolo Hospital (I.C., M.B.), and the Department of Obstetrics and Gynecology, Istituti Clinici di Perfezionamento (M.V.V.), University of Milan — all in Milan, Italy.

Address reprint requests to Dr. Martinelli at the Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, University of Milan, Via Pace, 9, 20122 Milan, Italy.

Full Text of this Article

This article has been cited by other articles:

• Tamura, T., Picciano, M. F. (2006). Folate and human reproduction. Am. J. Clin. Nutr. 83: 993-1016 [Abstract] [Full Text]  
• Ananth, C. V., Liu, S., Kinzler, W. L., Kramer, M. S. (2005). Stillbirths in the United States, 1981-2000: An Age, Period, and Cohort Analysis. Am. J. Public Health 95: 2213-2217 [Abstract] [Full Text]  
• Huber, A., Grimm, C., Jirecek, S., Zeillinger, R., Heim, K., Husslein, P., Hefler, L. (2005). An lnterleukin-6 Gene Promoter Polymorphism and Unexplained Late Intrauterine Fetal Death: A Multicenter Study. Reproductive Sciences 12: 33-36 [Abstract]  
• Frias, A. E. Jr, Luikenaar, R. A., Sullivan, A. E., Lee, R. M., Porter, T F., Branch, D W., Silver, R. M. (2004). Poor Obstetric Outcome in Subsequent Pregnancies in Women With Prior Fetal Death. Obstet Gynecol 104: 521-526 [Abstract] [Full Text]  
• Bates, S. M., Greer, I. A., Hirsh, J., Ginsberg, J. S. (2004). Use of Antithrombotic Agents During Pregnancy: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126: 627S-644S [Abstract] [Full Text]  
• Hurtado, V., Montes, R., Gris, J.-C., Bertolaccini, M. L., Alonso, A., Martinez-Gonzalez, M. A., Khamashta, M. A., Fukudome, K., Lane, D. A., Hermida, J. (2004). Autoantibodies against EPCR are found in antiphospholipid syndrome and are a risk factor for fetal death. Blood 104: 1369-1374 [Abstract] [Full Text]  
• Brenner, B. (2004). Clinical management of thrombophilia-related placental vascular complications. Blood 103: 4003-4009 [Abstract] [Full Text]  
• Hefler, L., Jirecek, S., Heim, K., Grimm, C., Antensteiner, G., Zeillinger, R., Husslein, P., Tempfer, C. (2004). Genetic Polymorphisms Associated With Thrombophilia and Vascular Disease in Women With Unexplained Late Intrauterine Fetal Death: A Multicenter Study. Reproductive Sciences 11: 42-44 [Abstract]  
• Carp, H., Dardik, R., Lubetsky, A., Salomon, O., Eskaraev, R., Rosenthal, E., Inbal, A. (2004). Prevalence of circulating procoagulant microparticles in women with recurrent miscarriage: a case-controlled study. Hum Reprod 19: 191-195 [Abstract] [Full Text]  
• Gris, J.-C., Perneger, T. V., Quere, I., Mercier, E., Fabbro-Peray, P., Lavigne-Lissalde, G., Hoffet, M., Dechaud, H., Boyer, J.-C., Ripart-Neveu, S., Tailland, M.-L., Daures, J.-P., Mares, P., Dauzat, M. (2003). Antiphospholipid/antiprotein antibodies, hemostasis-related autoantibodies, and plasma homocysteine as risk factors for a first early pregnancy loss: a matched case-control study. Blood 102: 3504-3513 [Abstract] [Full Text]  
• Zetterberg, H., Regland, B., Palmer, M., Rymo, L., Zafiropoulos, A., Arvanitis, D.A., Spandidos, D.A., Blennow, K. (2002). The transcobalamin codon 259 polymorphism influences the risk of human spontaneous abortion. Hum Reprod 17: 3033-3036 [Abstract] [Full Text]  
• Carp, H., Salomon, O., Seidman, D., Dardik, R., Rosenberg, N., Inbal, A. (2002). Prevalence of genetic markers for thrombophilia in recurrent pregnancy loss. Hum Reprod 17: 1633-1637 [Abstract] [Full Text]  
• Many, A., Elad, R., Yaron, Y., Eldor, A., Lessing, J. B., Kupferminc, M. J. (2002). Third-Trimester Unexplained Intrauterine Fetal Death Is Associated With Inherited Thrombophilia. Obstet Gynecol 99: 684-687 [Abstract] [Full Text]  
• Iwaki, T., Sandoval-Cooper, M. J., Paiva, M., Kobayashi, T., Ploplis, V. A., Castellino, F. J. (2002). Fibrinogen Stabilizes Placental-Maternal Attachment During Embryonic Development in the Mouse. Am. J. Pathol. 160: 1021-1034 [Abstract] [Full Text]  
• Lockwood, C. J. (2002). Inherited Thrombophilias in Pregnant Patients: Detection and Treatment Paradigm. Obstet Gynecol 99: 333-341 [Abstract] [Full Text]  
• Hefler, L. A., Tempfer, C. B., Bashford, M. T., Unfried, G., Zeillinger, R., Schneeberger, C., Koelbl, H., Nagele, F., Huber, J. C. (2002). Polymorphisms of the angiotensinogen gene, the endothelial nitric oxide synthase gene, and the interleukin-1{beta} gene promoter in women with idiopathic recurrent miscarriage. Mol Hum Reprod 8: 95-100 [Abstract] [Full Text]  
• Arkel, Y. S., Ku, D.-H. W. (2001). State-of-the-Art Review: Thrombophilia and Pregnancy: Review of the Literature and Some Original Data. CLIN APPL THROMB HEMOST 7: 259-268 [Abstract]  
• Bauer, K. A. (2001). The Thrombophilias: Well-Defined Risk Factors with Uncertain Therapeutic Implications. ANN INTERN MED 135: 367-373 [Abstract] [Full Text]  
• Seligsohn, U., Lubetsky, A. (2001). Genetic Susceptibility to Venous Thrombosis. NEJM 344: 1222-1231 [Full Text]  
• Macik, B. G., Rand, J. H., Konkle, B. A. (2001). Thrombophilia: What's a Practitioner to Do?. ASH Education Book 2001: 322-338 [Abstract] [Full Text]