Background The Factor V Leiden and prothrombin-gene mutationsare independent risk factors for venous thrombosis; it is debatedwhether a mutation in the gene encoding methylenetetrahydrofolatereductase, an enzyme involved in homocysteine metabolism, alsoincreases the risk of venous thrombosis. Whether any of thesemutations is associated with an increased risk of late fetaldeath is not known.
Methods We studied 67 women with a first episode of unexplainedlate fetal loss (fetal death after 20 weeks or more of gestation)and 232 women who had had one or more normal pregnancies andno late fetal losses. All the women were tested for the presenceof three gene mutations. Women with other thrombophilic conditionswere 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 factorV or the prothrombin mutation. The relative risks of late fetalloss in carriers of the factor V and prothrombin mutations were3.2 (95 percent confidence interval, 1.0 to 10.9) and 3.3 (95percent confidence interval, 1.1 to 10.3), respectively. Thirteenpercent of the women whose fetuses died and 20 percent of thecontrol women were homozygous for the mutation in the methylenetetrahydrofolatereductase gene (relative risk, 0.8; 95 percent confidence interval,0.5 to 1.2).
Conclusions Both the factor V and the prothrombin mutationsare associated with an approximate tripling of the risk of latefetal 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.
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