Low-Dose Aspirin Does Not Prevent Pre-eclampsia in High-Risk Women
Source: Caritis S, et al. N Engl J Med 1998;338:701-705.
To determine whether low-dose aspirin prevents pre-eclampsia in women at increased risk, a multicenter double-blind, randomized, placebo-controlled trial was conducted in women with pregestational insulin-treated diabetes mellitus (n = 471), women with chronic hypertension (n = 774), women with multifetal gestations (n = 688), and women who had had pre-eclampsia in a prior pregnancy (n = 606). Patients entered the trial between 13-26 weeks gestation.The incidence of pre-eclampsia was nearly identical in the 1254 who received 60 mg of aspirin daily (18%) when compared to the 1249 women in the placebo group (20%). No difference was observed in the occurrence of pre-eclampsia in any of the four high-risk groups when patients who received aspirin were compared to patients given the placebo. Examination of important variables, including entry into the study before or after 20 weeks gestation, gestational age at the time of delivery, systolic blood pressure at the start of the study, parity, or race, revealed no effect of aspirin treatment. Aspirin was not associated with an increase in adverse outcomes, including postpartum hemorrhage, placental abruption, perinatal death, or neonatal intraventricular hemorrhage.
Caritis and colleagues conclude that prophylactic low-dose aspirin does not reduce the incidence of pre-eclampsia in women at increased risk for this complication.
Comment by Steven G. Gabbe, MD
This important investigation from the Multicenter Maternal Fetal Medicine Network of the National Institute of Child Health and Human Development demonstrates that low-dose aspirin begun in the second trimester of pregnancy does not lower the risk of pre-eclampsia in women at high risk for this complication. Caritis et al have reported earlier that pre-eclampsia is not reduced in nulliparous patients who were given low-dose aspirin. That this trial was conducted in a high-risk patient population is demonstrated by the occurrence of pre-eclampsia in 20% of women in the placebo group. While smaller trials have suggested that aspirin might be an effective prophylaxis for pre-eclampsia, this and other larger studies, which have included a total of nearly 28,000 patients, confirm the lack of efficacy. As I examine the data in this study, several questions do remain.
First, would the incidence of pre-eclampsia be reduced by aspirin started in the first trimester, a critical period for placentation? Second, of the 471 women with pregestational diabetes in this trial, only 13% had vasculopathy. Would an effect have been seen if a larger group of diabetic women with vasculopathy had been studied-especially women with nephropathy?
Dr. Gabbe is Professor and Chairman, Department of OB/GYN, University of Washington School of Medicine, Seattle.