Maternal and paternal thrombophilia : Risk factors for perinatal mortality

Maternal thrombophilia is an accepted risk factor for perinatal death, having been associated with pregnancy-related thrombosis and preeclampsia, intrauterine growth restriction, placental abruption, recurrent miscarriage, and late fetal loss. Up to two thirds of these vascular complications can be related to some form of inherited or acquired thrombophilia. It is not clear whether paternal factors contribute to thrombophilia-related perinatal mortality. The investigators examined data from a prospective registry of perinatal mortality in The Netherlands. Seventy-four women with a previous perinatal death and 54 of their male partners were assessed, along with 71 women having uneventful pregnancies and 66 of their partners. Cases and control subjects did not differ with respect to age or oral contraceptive use. Compared with control women, case women had significant higher rates of antithrombin deficiency (12% vs. 0%), elevated factor VIII activity (43% vs. 17%), and increased activated protein C (APC) resistance (32% vs. 6%). Total protein S antigen also was increased in case women. There were no significant group differences in the prevalence of deficient protein C activity, hyperhomocysteinemia, factor V G1691A (F V Leiden) mutation, prothrombin mutation, or the MTHFR C677T mutation. The overall prevalence of one or more thrombophilic factors was 70% in case women and 30% in control women. Male cases had significantly increased APC resistance compared with the male control group (22% vs. 0%). Of 54 couples with past perinatal mortality, 30 (55%) had more than one thrombophilic abnormality compared with 10 (17%) of control couples. The prevalence of thrombophilia is about doubled not only in mothers, but also in fathers having a history of perinatal mortality, suggesting that it is a risk factor.