Low-dose aspirin increases 15-epi-lipoxins A4 in pregnancies at high-risk for developing preeclampsia.

Abstract

LDA triggers biosynthesis of endogenous anti-inflammatory molecules, aspirin-triggered 15-epi-lipoxin A4 (15-epi-LXA4), which may counteract inflammatory process of preeclampsia (PE), and play role in LDA's mechanism of action in PE prevention in high-risk patients. Investigate the effects of daily LDA on levels of 15-epi-LXA4 in pregnancies at high-risk for developing PE. Secondary analysis of multi-centered randomized controlled trial investigating effects of daily LDA (60mg) in high-risk pregnancies. Maternal samples were drawn at three points: before LDA initiation (13-26weeks' gestation), 24-28weeks' gestation (at least two weeks after LDA) and 34-36weeks' gestation. 15-epi-LXA4 levels were measured by ELISA. Analysis included 82 patients: 63 receiving daily LDA and 29 receiving daily placebo starting between 13 and 25weeks gestation. Prior to randomization, baseline 15-epi-LXA4 levels were similar between both groups (75.9pg/mL [IQR; 63.8-114.0] vs 136.2pg/mL [52.4-476.2]; p=0.10). Patients receiving daily LDA were noted to have significantly increased levels of 15-epi-LXA4 after LDA administration (136.2pg/mL [IQR; 52.4-476.2] vs 1758.2pg/mL [905.4-6638.5]; p<0.001). They also had higher 15-epi-LXA4 levels compared to those receiving placebo at 24-28weeks' (50.3 [38.1-94.2] vs 1758.2 [905.4-6638.5]; p<0.001 and 34-38weeks' gestation (57.9 [41.9-76.7] vs 2310.3pg/mL [656.9-10609.4]; p<0.001). After LDA administration in the second trimester, patients who developed PE had decrease in 15-epi-LXA4 levels compared to those without PE (942pg/mL [348.3-1810.3] vs 1758.2pg/mL [905.4-6638.5]; p=0.129). Daily LDA administration increases 15-epi-LXA4 levels in high-risk pregnancies for PE. In LDA group, pregnancies complicated by PE have lower levels of 15-epi-LXA4 compared to pregnancies without PE.