Aspirin Versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia

Abstract

Since 1979, multiple studies have shown that low-dose aspirin in pregnancy can lower the occurrence of preeclampsia. Subsequent studies have shown that doses greater than 100 mg/d started before 16 weeks of gestation are most effective. Another recent study found that screening pregnant women for preeclampsia risk based on a combination of maternal factors and biochemical and physical measurements early in pregnancy could identify heightened risk of preeclampsia twice as well as predicting risk based on history alone. In this trial (the CombinedMultimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-based Preeclampsia Prevention [ASPRE trial]), women identified as being at high risk of developing preeclampsia were treated with daily low-dose aspirin and compared with women who were treated with placebo. A double-blind randomized controlled trial was performed to assess the impact of 150 mg of aspirin daily from 11 to 14 weeks until 36 weeks of pregnancy in a group of women who were screened and found to be at high risk of preeclampsia. A total of 1776 women with singleton pregnancies were enrolled in the trial, which was analyzed on an intention-to-treat basis. After some women dropped out of the trial and some were lost to follow-up, there remained 822 participants in the placebo group and 798 in the aspirin group. Of these participants, 4.3% of the placebo group and 1.6% of the aspirin group developed preeclampsia before 37 weeks' gestation (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20-0.74; P = 0.004). The occurrence of adverse outcomes such as miscarriage or stillbirth was not significantly different between the 2 groups. Sensitivity analyses showed that these results were not affected by the enrollees who dropped out of the trial by either choice or loss at follow-up. Compliance of participants was good, with nearly 80% taking 85% of their required aspirin doses. This study confirmed that a regimen of low-dose aspirin (150 mg/d) during pregnancy can lower the occurrence of preeclampsia in susceptible populations. In this trial, preeclampsia was reduced by more than half in women taking aspirin as compared with those taking a placebo.