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Use of Prophylactic Aspirin in Preventing Preeclampsia
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Am Fam Physician. 1998 Aug 1;58(2):516-518.
The use of prophylactic aspirin for the prevention of preeclampsia has been recommended on the basis of several small studies. The rationale for its recommendation is that aspirin inhibits thromboxane production more than prostacyclin production and therefore should prevent vasoconstriction and pathologic coagulation in the placenta. Caritis and colleagues conducted a randomized, double-blind, placebo-controlled trial to determine if aspirin reduced the incidence of preeclampsia in women at increased risk for developing this disease during pregnancy.
Women enrolled in the trial were screened at 13 different study sites. The researchers selected women in one of four high-risk groups. These groups included women with pregestational type 1 diabetes mellitus, women with multiple gestations, women with chronic hypertension and women who had had preeclampsia in a previous pregnancy. Patients were entered into the study between 13 and 26 weeks of pregnancy. They were given either 60 mg of aspirin or a placebo tablet once daily. Prenatal visits occurred every four weeks until week 28 of the pregnancy, then every two weeks until week 36, and then weekly until delivery. Patients were instructed to take their medication until delivery but were to discontinue it if preeclampsia developed. The primary outcome measured was preeclampsia, which was defined as the development of hypertension plus one of the following: proteinuria, thrombocytopenia or pulmonary edema. Hypertension was defined as a systolic blood pressure of 140 mm Hg or greater, or a diastolic blood pressure of 90 mm Hg or greater, on two occasions at least four hours apart. Proteinuria was defined as the excretion of 300 mg of protein in a 24-hour urine collection, or two dipstick test results that were 2+ or greater. Thrombocytopenia was defined as a platelet count of less than 100,000 per mm3 (100,000 × 109 per L).
Between 1991 and 1995, over 2,500 women were enrolled in the study, with one half of them receiving aspirin and the other half receiving placebo. There were no significant differences between the two groups in mean age, gravidity, mean week of gestation at entry into the study and race. At the end of the study, there was no difference in the incidence of preeclampsia between the aspirin group and the placebo group. This finding remained after each of the four risk groups were evaluated individually. The overall incidence of preeclampsia was quite high, at 20 percent for the placebo group and 18 percent for the aspirin group. Secondary outcomes, including incidence of preterm birth, infants born small for gestational age, perinatal deaths, abruptio placentae, postpartum hemorrhage and intraventricular hemorrhage, were not different between the two groups.
The researchers conclude from their study that low-dose aspirin does not prevent preeclampsia in high-risk women and therefore should not be administered to women in this group. On a positive note, the use of aspirin did not adversely affect the mothers or their infants.
Caritis S, et al. Low-dose aspirin to prevent preeclampsia in women at high risk. N Engl J Med. March 12, 1998;338:701–5.
Copyright © 1998 by the American Academy of Family Physicians.
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