ASPRE trial: effects of aspirin on mean arterial blood pressure and uterine artery pulsatility index trajectories in pregnancy
AbstractThe mechanism by which aspirin prevents pre-eclampsia is poorly understood, and its effects on biomarkers throughout pregnancy are unknown.
Aim. We aimed to investigate the effects of aspirin on mean arterial pressure (MAP) and mean uterine artery pulsatility index (UtA-PI) using repeated measures from women at increased risk of preterm pre-eclampsia.
Methods. This was a longitudinal secondary analysis of the Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Pre-eclampsia Prevention (ASPRE) trial using repeated measures of MAP and UtA-PI. In the trial, 1620 women at increased risk of preterm pre-eclampsia were identified using the Fetal Medicine Foundation algorithm at 11+0 to 13+6 weeks, of whom 798 were randomly assigned to receive 150 mg/day aspirin and 822 were assigned to receive placebo daily from 11–14 weeks to 36 weeks of gestation or delivery, whichever came first. MAP and UtA-PI were measured at baseline and follow-up visits at 19–24, 32–34 and 36 weeks of gestation. Generalized additive mixed models with treatment by gestational age interaction terms were used to investigate the effects of aspirin on MAP and UtA-PI trajectories over time.
Results. Among 798 participants in the aspirin group and 822 in the placebo group, there were 5951 MAP and 5942 UtA-PI measurements. Trajectories of raw and multiples of the median (MoM) values of MAP did not differ significantly between the two groups (MAP MoM analysis: P-value for treatment by gestational age interaction, 0.340). In contrast, trajectories of raw and MoM values of UtA-PI showed a significantly steeper decline in the aspirin group than in the placebo group, with the difference mainly driven by a more pronounced reduction before 20 weeks of gestation (UtA-PI MoM analysis: P-value for treatment by gestational age interaction, 0.006).
Conclusion. In women at increased risk of preterm pre-eclampsia, 150 mg/day aspirin initiated in the first trimester does not affect MAP but is associated with a significant decrease in mean UtA-PI, particularly before 20 weeks of gestation.
What are the novel findings of this work? Aspirin is effective in preventing preterm pre-eclampsia, but its precise mechanism of action remains unknown. In this secondary longitudinal analysis of the ASPRE trial, aspirin had no evident effect on the trajectory of mean arterial pressure values over time but led to a steeper decline in uterine artery pulsatility index, particularly before 20 weeks of gestation.
What are the clinical implications of this work? We found no evidence of antihypertensive effects of aspirin in pregnancy. The significant difference in uterine artery pulsatility index trajectory between high-risk women who receive aspirin compared with those who do not, particularly before 20 weeks of pregnancy, may suggest an improvement in trophoblastic invasion and uteroplacental perfusion.
Keywords:aspirin; ASPRE trial; first trimester; mean arterial pressure; pre-eclampsia; prevention; uterine artery Doppler
Rolnik D.L., Syngelaki A., O’Gorman N., Wright D., Poon L.C., Nicolaides K.H. ASPRE trial: effects of aspirin on mean arterial blood pressure and uterine artery pulsatility index trajectories in pregnancy. Obstet Gynecol 2023; 61: 691–7. DOI: https://doi.org/10.1002/uog.26222
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