Considerable maternal and perinatal mortality and morbidity are associated with placental-mediated pregnancy complications. Preventative options are limited. Because thrombosis is frequently observed in the uteroplacental circulation of women with placental-mediated pregnancy complications, a number of studies have investigated anticoagulation therapy using unfractionated heparin or low-molecular-weight heparin as a preventative option. Most such studies were conducted in women with thrombophilia; the limited data available for women without thrombophilia are unconvincing. This pilot randomized controlled trial evaluated the effectiveness of dalteparin, a low-molecular-weight heparin, in preventing the recurrence of placental-mediated pregnancy complications in women without thrombophilia who are at high risk for these complications. A total of 114 pregnant women were randomized to receive dalteparin (study group, n = 57) or no dalteparin (control group, n = 57). Inclusion criteria at randomization were gestational age <17 weeks, absence of thrombophilia, and occurrence in the immediate previous pregnancy of one or more of the following: severe preeclampsia, unexplained newborn weight ≤ the fifth percentile, abruptio placentae, or unexplained intrauterine death. Women in the study group received dalteparin for 23.0 ± 7.0 weeks. The primary outcome was a composite of one or more of the following: severe preeclampsia, newborn weight ≤ the fifth percentile or major abruptio placentae resulting in delivery before 34 weeks’ gestation. Data were available for 110 women in the final analysis.
The primary outcome occurred less frequently in the study group than the control group (5.5% [3 of 55] vs. 23.6% [13 of 55]); the adjusted odds ratio was 0.15, with a 95% confidence interval of 0.03–0.70). No statistically significant differences between the 2 groups were found for the secondary outcomes of nonsevere preeclampsia, birth weight between sixth and 10th percentile and gestational age at delivery. Neither heparin-induced thrombocytopenia nor hemorrhage was observed in the women receiving dalteparin.
The findings in this pilot study show that the recurrence of placental-mediated complications in women without thrombophilia is reduced by prophylactic doses of dalteparin, but the results require confirmation in larger randomized trials.
Division of Obstetrics Medicine, Department of Obstetrics and Gynaecology, CHU Sainte-Justine, Montreal, QC, Canada; Medicine, Hôpital Maisonneuve-Rosemont; Division of Haematology, Department of Paediatrics, CHU Sainte-Justine, Montreal, QC, Canada; Department of Obstetrics and Gynaecology, CHU Sainte-Justine; Division of Haematology, Department of Medicine, Montreal, QC, Canada; Hôpital Enfant-Jésus, Quebec, QC, Canada; Department of Medicine, SMBD Jewish General Hospital, Montreal, QC, Canada; British Columbia Women’s Hospital and Health Center, Department of Medicine, Vancouver, BC, Canada; and Division of Hematology, Department of Medicine, Ottawa Hospital, Ottawa, ON, Canada
J Thromb Haemost 2009;7:58–64