Aspirin for evidence-based preeclampsia prevention trial: effects of aspirin on maternal serum pregnancy-associated plasma protein A and placental growth factor trajectories in pregnancy

Abstract

BackgroundThe exact mechanism by which aspirin prevents pre-eclampsia (PE) remains unclear. Its effects on serum placental biomarkers throughout pregnancy are also unknown. ObjectiveTo investigate the effects of aspirin on serum pregnancy-associated plasma protein A (PAPP-A) and placental growth factor (PlGF) trajectories using repeated measures from women at increased risk of preterm PE. Study DesignThis was a longitudinal secondary analysis of the Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-based Preeclampsia Prevention (ASPRE) trial using repeated measures of PAPP-A and PlGF. In the trial, 1,620 women at increased risk of preterm PE were identified using the Fetal Medicine Foundation algorithm at 11-13+6 weeks, of whom 798 were randomly assigned to receive aspirin 150 mg and 822 to receive placebo daily from before 14 weeks to 36 weeks of gestation. Serum biomarkers were measured at baseline and follow-up visits at 19 to 24, 32 to 34, and 36 weeks of gestation. Generalized additive mixed models with treatment by gestational age interaction terms were used to investigate the effect of aspirin on biomarker trajectories over time. ResultsOverall, there were 5,507 PAPP-A and 5,523 PlGF measurements. Raw PAPP-A values increased over time, and raw PlGF increased until 32 weeks of gestation followed by a decline. The multiple of the median (MoM) mean values of the same biomarkers were consistently below 1.0 MoM, reflecting the high-risk profile of the study population. Trajectories of mean PAPP-A and PlGF MoM values did not differ significantly between the aspirin and placebo groups (aspirin treatment by gestational age interaction p-values: 0.259 and 0.335, respectively). ConclusionsIn women at increased risk of preterm PE, aspirin 150 mg daily had no significant effects on PAPP-A or PlGF trajectories when compared to placebo.