Platelet-Associated microRNAs as Markers of Aspirin Response and Pregnancy Outcome in Pregnancies at High-Risk for Preeclampsia

Aspirin is recommended in high-risk pregnancies for the prevention of preeclampsia/preterm birth; it is unclear whether aspirin's antiplatelet or anti-inflammatory (or both) effects drive its efficacy, and there are no established markers of therapeutic efficacy for pregnancy-specific outcomes. MicroRNAs (miR) are noncoding posttranscriptional modifiers implicated in preeclampsia/preterm birth and platelet function. We aimed to evaluate whether selected platelet-associated miRs were associated with platelet inhibition following aspirin use and associated with perinatal outcomes.This is a planned secondary analysis of a cohort of high-risk singleton pregnancies taking aspirin. Participants had bloodwork done in the first trimester, preaspirin, 2 to 4 weeks after aspirin initiation (follow-up 1), and at 28 to 32 weeks of gestation (follow-up 2). We selected six platelet-associated miRs (16, 18a, 126, 155, 181a, and 223) that are also associated with preeclampsia and reported quantity as fold-change from baseline (follow-up/baseline). We evaluated with univariate analysis the relationship between miR fold-change at follow-up visits 1 and 2 with Platelet Function Assay-100 epinephrine closure time (PFA-100, Siemens), a measure of aspirin response. We also evaluated the relationship between miR fold-change from baseline at each visit and the outcome of (1) hypertensive disorders of pregnancy (HDP): preeclampsia or gestational hypertension and (2) preterm birth < 37 weeks.Of the original cohort, 57 were included in this secondary analysis. The fold-change in miR-223 and miR-18a significantly decreased with increasing PFA-100 epinephrine closure time. Twelve (21%) pregnancies had HDP, and eight (14%) had preterm birth < 37 weeks. Four preterm births were due to severe preeclampsia, and one was preeclampsia without severe features and spontaneous labor. Fold-change in miRs was not associated with HDP, but increased miR-223 at 28 to 32 weeks was significantly associated with an increased risk of preterm birth (odds ratio: 2.77 [1.21-6.87]; <i>p</i> = 0.04).Selected platelet-associated miRs may be promising markers to assess the therapeutic effect of aspirin in pregnancy and warrant further exploration. · Platelet-associated miR decreases in association with platelet inhibition.. · Elevated miR-223 in the third trimester may be associated with preterm birth.. · Platelet-associated miR may be a marker of aspirin therapeutic effect in pregnancy..