The Use of Aspirin to Prevent Ppregnancy-Induced Hypertension and Lower the Ratio of Thromboxane A₂ to Prostcyclin in Relatively High Risk Pregnancies

We carried out a prospective, randomized, double-blind, placebo-controlled study to investigate the capacity of aspirin to prevent pppregnancy-induced hypertension and to alter prostaglandin metabolism. A total of 791 pregnant women with various risk factors for preeclamptic toxemia were screened with use of the rollover test (a comparison of blood pressure before and after the woman rolls from her left side to her back) during week 28 or 29 of gestation. Of 69 women with abnormal results (an increase in blood pressure during the rollover test), 65 entered the study and were treated with a daily dose of either aspirin (100 mg; 34 women) or placebo (31 women) during the third trimester of pregnancy. The number of women in whom pppregnancy-induced hypertension developed was significantly lower among the aspirin-treated than among the placebo-treated women (4 [11.8 percent] vs. 11 [35.5 percent]; P = 0.024); the same was true for the incidence of preeclamptic toxemia (1 [2.9 percent] vs. 7 [22.6 percent]; P = 0.019). The mean ratio of serum levels of thromboxane A₂ to serum levels of prostacyclin metabolites after three weeks of treatment decreased by 34.7 percent in the aspirin-treated group but increased by 51.2 percent in the placebo-treated group. No serious maternal or neonatal side effects of treatment occurred in either group. We conclude that low daily doses of aspirin taken during the third trimester of pregnancy significantly reduce the incidence of pppregnancy-induced hypertension and preeclamptic toxemia in women at high risk for these disorders, possibly through the correction of an imbalance between levels of thromboxane and prostacyclin. (N Engl J Med 1989;321:351–6.) PREECLAMPTIC toxemia of pregnancy is still a major cause of obstetrical and perinatal morbidity and mortality,¹ and no breakthrough has yet been achieved in the understanding of its pathophysiology or in the development of a specific treatment or means of prevention. Three principal mechanisms have been suggested for this disorder: increased vasospasm caused by an abnormal sensitivity of vascular smooth muscle to pressor substances,² an abnormal maternal immunologic reaction,³ and an imbalance in the production of vasoactive prostaglandins (thromboxane A₂ and prostacyclin), leading to the vasoconstriction of small arteries and the activation of platelets.^{4 5 6} Prostacyclin, a very potent vasodilator.