OP13.01: *Effective aspirin treatment for women at risk of pre‐eclampsia delays the metabolic clock of gestation

To evaluate the effect of low-dose aspirin on delaying the metabolic gestational clock of gestation in high-risk women for pre-eclampsia (PE). This study utilised archived plasma samples from two trials: 58 high-risk aspirin-treated women in the FORECAST trial (NCT03941886) and 52 high-risk placebo-treated women in the ASPRE trial (ISRCTN13633058). Women were considered high-risk women for preterm PE if they had an adjusted risk ≥1 in 100 following the first trimester Fetal Medicine Foundation combined test. Plasma samples were collected at 11-16 weeks, before either aspirin or placebo treatment, and at 20-23 weeks and 30-37 weeks, after either aspirin or placebo treatment. Untargeted metabolomics profiling was performed on 151 and 139 plasma samples in the aspirin and placebo groups, respectively. Among the participants in the aspirin group, 27/58 developed PE. In the placebo group, 30/52 women had PE. A metabolic clock of gestation was constructed using an orthogonal partial least squares discriminant analysis model that predicts gestational age. The model was constructed using metabolomic data of the pretreatment and the placebo-treated samples. Comparing pre-eclamptic or non-pre-eclamptic clinical outcomes in response to treatment, we identified 78 significantly different metabolites (p < 0.05). Pre-eclamptic samples were dominated by higher levels of steroids, long-chain fatty acids (LCFAs), very long-chain fatty acids (VLCFAs), and lipids containing LCFA or VLCFA branches. Aspirin altered seven of these differential metabolites. In the aspirin-treated group, gestational age acceleration significantly deviated from zero in a negative direction by 2.88 weeks and 3.99 weeks on average in the second and third trimesters, respectively. We have demonstrated that aspirin significantly decreases the metabolic clock of gestation. These results support the hypothesis that aspirin delays the gestational age at delivery with PE.