Increased frequency of genetic thrombophilia in women with complications of pregnancy

Background Obstetrical complications such as severe preeclampsia, abruptio placentae, fetal growth retardation, and stillbirth are associated with int ervillous or spiral-artery thrombosis and inadequate placental perfusion. W hether these complications are associated with an increased frequency of th rombophilic mutations is not known. Methods We studied 110 women who had one of the above-mentioned obstetrical complications and 110 women who had one or more normal pregnancies. The wo men were tested several days after delivery for the mutation of adenine to guanine at nucleotide 506 in the factor V gene (factor V Leiden), the mutat ion of cytosine to thymine at nucleotide 677 in the gene encoding methylene tetrahydrofolate reductase, and the mutation of guanine to adenine at nucle otide 20210 in the prothrombin gene. Two to three months after delivery the women were tested for deficiency of protein C, protein S, or antithrombin III and for the presence of anticardiolipin antibodies. Results The mutation at nucleotide 506 in the factor V gene was detected in 22 of the women with obstetrical complications and in 7 of the women with normal pregnancies (20 percent and 6 percent, respectively; P=0.003). Twent y-four women with complications, as compared with nine women without compli cations, were homozygous for the C677T mutation in the gene encoding methyl enetetrahydrofotate reductase (22 percent and 8 percent, respectively; P=0. 005). The G20210A mutation in the prothrombin gene was found in 11 women wi th complications as compared with 3 women without complications (10 percent and 3 percent, respectively; P=0.03). Overall, 57 women with obstetrical c omplications had a thrombophilic mutation, as compared with 19 women with n ormal pregnancies (52 percent and 17 percent, respectively; P<0.001). Defic iency of protein S, protein C, or antithrombin ill or anticardiolipin antib odies were detected in an additional 14 women with complications, as compar ed with 1 woman with a normal pregnancy (13 percent and 1 percent, respecti vely; P<0.001). Conclusions Women with serious obstetrical complications have an increased incidence of mutations predisposing them to thrombosis and other inherited and acquired forms of thrombophilia. (N Engl J Med 1999;340:9-13.) (C) 1999 , Massachusetts Medical Society.