Circulating Extracellular Vesicles Suggest Race-Associated Transcriptomic Differences in Preterm Birth: A Pilot Study.

Preterm birth (PTB) remains a leading cause of neonatal morbidity and mortality and disproportionately affects Black women in the United States. While racial disparities in PTB are well documented, the molecular pathways underlying these differences remain incompletely understood. Extracellular vesicles (EVs) are circulating lipid-bound particles that carry coding and non-coding RNAs reflecting cellular stress states and may serve as integrative molecular indicators of pregnancy biology. In this hypothesis-generating pilot study, EVs were isolated from maternal plasma collected at delivery from non-Hispanic Black and non-Hispanic White women with preterm and full-term births. EV concentration and size were assessed, and EV-associated mRNA and miRNA cargo were profiled by next-generation sequencing (n = 5 per group), enabling differential expression and pathway enrichment analyses stratified by gestational outcome. EV concentrations were significantly elevated in PTB compared with full-term deliveries (p < 0.0001), with a greater increase among Black participants. Analysis of EV-associated mRNA transcripts identified a shared signature enriched for platelet activation and coagulation pathways across racial groups. Race-stratified analyses revealed distinct EV miRNA profiles in PTB, with enrichment of cytokine-mediated signaling pathways among Black participants and apoptosis-related pathways among White participants, while a subset of miRNAs differed by race independent of gestational outcome. These findings support EV profiling as a framework to investigate biological pathways contributing to PTB disparities.