Aspirin delays the development of preeclampsia

Abstract

Background: In the Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention trial, risks of preterm preeclampsia were obtained from the competing risk model. Consenting women with risks of greater than 1 in 100 were randomized to treatment with aspirin or placebo. The trial showed strong evidence of an effect (odds ratio, 0.38, 95% confidence interval, 0.20-0.74) on the incidence of preterm preeclampsia, which was the primary outcome of Aspirin for Evidence-Based Preeclampsia Prevention. There was a small and insignificant effect on the incidence of term preeclampsia, which was a secondary outcomes (odds ratio, 0.95, 95% confidence interval, 0.64-1.39). These differential effects on term and preterm preeclampsia could reflect a mechanism in which the action of aspirin is to delay the delivery with preeclampsia, thereby converting what would be, without treatment, preterm preeclampsia to term preeclampsia.

Objective: The objective of the study was to examine the hypothesis that the effect of aspirin is to delay the time of delivery in women who have preeclampsia.

Study design: This was an unplanned exploratory analysis of data from the Aspirin for Evidence-Based Preeclampsia Prevention trial. The delay hypothesis predicts that in groups for which preterm preeclampsia, without aspirin, were infrequent relative to term preeclampsia, a reduction in term preeclampsia would be expected because few cases of preterm preeclampsia would be converted to term preeclampsia. In contrast, in groups for which preterm preeclampsia were frequent relative to term preeclampsia, the conversion of preterm preeclampsia to term preeclampsia by aspirin would reduce or even reverse any effect on the incidence term preeclampsia. This is examined using the Aspirin for Evidence-Based Preeclampsia Prevention trial data by analysis of the effect of aspirin on the incidence of term preeclampsia stratified according to the risk of preterm preeclampsia at randomization. Given that women were included in Aspirin for Evidence-Based Preeclampsia Prevention with risks of preterm preeclampsia >1 in 100, a risk cutoff if 1 in 50 was used to define higher risk and lower risk strata. A statistical model in which the effect of aspirin is to delay the gestational age at delivery was fitted to the Aspirin for Evidence-Based Preeclampsia Prevention trial data and the consistency of the predictions from this model with the observed incidence was demonstrated.

Results: In the lower-risk group (<1 in 50), there was a reduction in the incidence of term preeclampsia (odds ratio, 0.62, 95% confidence interval, 0.29-1.30). In contrast, in the higher risk group (≥1 in 50) there was a small increase in the incidence of term- preeclampsia (odds ratio 1.11, 95% confidence interval, 0.71- .75). Although these effects fail to achieve significance, they are consistent with the delay hypothesis. Within the framework of the aspirin-related delay hypothesis, the effect of aspirin was to delay the gestational age at delivery with preeclampsia by an estimated 4.4 weeks (95% confidence interval, 1.4-7.1 weeks) for those that in the placebo group would be delivered at 24 weeks and the effect decreased by an estimated 0.23 weeks (95% confidence interval, 0.021-0.40 weeks) for each week of gestation so that at 40⁺⁰ weeks, the estimated delay was by 0.8 weeks (95% confidence interval, -0.03 to 1.7 weeks).

Conclusion: The Aspirin for Evidence-Based Preeclampsia Prevention trial data are consistent with the hypothesis that aspirin delays the gestational age at delivery with preeclampsia.

Keywords: Aspirin for Evidence-Based Preeclampsia Prevention trial; aspirin; competing risks model; first-trimester screening; preeclampsia; pregnancy; preterm delivery; pyramid of pregnancy care; term delivery.