OP 56 Dalteparin promotes fetal and placental growth in the reduced uterine perfusion pressure model of preeclampsia

Introduction Severe early-onset preeclampsia is caused by defects in placentation and subsequent placental dysfunction, often resulting in an imbalance of circulating angiogenic molecules including sFlt1 and PlGF that mediate many manifestations of the disease. Low-molecular-weight heparins (LMWHs) such as Dalteparin may prevent early severe preeclampsia although recent randomized clinical trials showed no benefit for overall disease prevention. Examining the effects of LMWH in an animal model will provide valuable insights into the potential impact of LMWH therapy in severe preeclampsia. Objective Investigate the effects of Dalteparin in the reduced uterine perfusion pressure (RUPP) model of preeclampsia. Methods The RUPP model of preeclampsia was induced in the pregnant rat by using silver clips to restrict blood perfusion into the uteroplacental circulation beginning gestation day (GD) 14. By GD19 the rats exhibited features of preeclampsia including new-onset hypertension, angiogenic imbalance, intrauterine growth restriction, and fetal loss. Daily subcutaneous injections of low-dose Dalteparin (saline in control RUPP animals) commenced on GD15 until GD19, when blood pressure was measured via carotid catheterization in the anaesthetized animal prior to sacrifice. Values are reported as mean ± SEM. Results Compared to sham-operated animals ( n  = 6), RUPP rats ( n  = 6) displayed significantly elevated mean arterial blood pressure (MAP; 85 ± 5 vs 102 ± 2 mmHg), greater fetal resorption (0 ± 0 vs 61 ± 8%), and lower average placental (0.56 ± 0.02 vs 0.50 ± 0.01 g) and fetal (2.56 ± 0.08 vs 2.15 ± 0.04 g) weights. Daily low-dose Dalteparin ( n  = 8) did not decrease MAP in RUPP rats (105 ± 3 mmHg); however, treatment improved placental (0.56 ± 0.02 g) and fetal (2.49 ± 0.04 g) weights. No effect of Dalteparin on fetal loss was observed (56 ± 7%). Conclusion Although Dalteparin did not ameliorate the elevated blood pressure in RUPP animals, treatment improved placental and fetal growth, which are important aspects in the management of severe preeclampsia. Early administration of LMWH in a subset of patients at high risk of early-onset, placenta-driven severe preeclampsia may support placental growth and prevent extreme preterm delivery due to severe dysfunction.