Extracellular Vesicles at the Intersection of Environmental Exposure and Preterm Birth: A Research Agenda for an Emerging Field

Preterm birth (PTB), defined as delivery before 37 completed weeks of gestation, affects approximately 10% of pregnancies in the United States and remains a leading cause of neonatal morbidity and mortality. Persistent disparities in PTB rates are not fully explained by traditional risk factors, highlighting the need for biomarkers of environmental exposures and their biological effects during pregnancy. While direct human evidence linking environmental exposures to extracellular vesicle (EV) alterations that contribute to PTB remains limited, this review examines whether EVs provide a plausible, testable framework linking environmental exposures with maternal-fetal signaling relevant to PTB risk. Maternal exposure to environmental pollutants and adverse neighborhood-level conditions, which disproportionately burden marginalized communities, has been associated with increased PTB risk. These exposures have been associated with inflammatory, metabolic, and epigenetic alterations, some of which are reflected in the cargo of circulating EVs, and profiling of maternal plasma EVs has identified signatures enriched for inflammatory and coagulation pathways among women who deliver preterm. Most of this evidence derives from non-reproductive toxicology, related pregnancy complications or biological plausibility, rather than from studies directly evaluating whether EVs mediate the effects of environmental exposures on PTB risk. Integrating EV biology with environmental health research offers a noninvasive framework for capturing the impact of environmental exposures on maternal-fetal signaling during pregnancy. Owing to the lack of direct human evidence, we present this as a forward-looking research agenda and outline the prospective, exposure-characterized studies needed to determine whether EV-based biomarkers can improve PTB risk stratification.