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August 26, 2025

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

RBRupsa C. BoeligThomas Jefferson University ATAntonios TawkThomas Jefferson University TZTingting ZhanThomas Jefferson University

Key Points

Increased mir-223 levels during late pregnancy doubled the risk of preterm birth in high-risk women, suggesting a significant association with aspirin response.
Among 57 participants, 21% experienced hypertensive disorders of pregnancy, while 14% faced preterm birth, indicating notable pregnancy complications in this cohort.
Univariate analysis revealed that specific platelet micrornas could reflect aspirin's therapeutic effects, highlighting their potential as predictive markers.
Findings imply that measuring platelet micrornas may enhance risk assessment and treatment strategies for high-risk pregnancies.

Abstract

Abstract 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; p = 0.04). Selected platelet-associated miRs may be promising markers to assess the therapeutic effect of aspirin in pregnancy and warrant further exploration.

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