Preeclampsia Prediction: The Role of Placental Biomarkers in Enhancing Maternal Care

Placental viral-derived enhancers may enable earlier risk stratification for preeclampsia; a multicenter analysis identifies 87 such enhancers and nominates EPS8L1 as a circulating biomarker candidate.

The multicenter case-control study of placental tissue from pregnancies with and without hypertensive complications replicated 87 virus-derived enhancers that regulate nine genes repeatedly dysregulated in preeclampsia, with consistent upregulation of EPS8L1 across cohorts.

In placental cell models, EPS8L1 overexpression reduced trophoblast invasion and disrupted angiogenic behavior; complete knockout caused cell death, indicating an essential role in trophoblast viability. These functional data make EPS8L1 a mechanistically plausible contributor to preeclampsia pathogenesis.

A secreted form of EPS8L1 is detectable in maternal plasma and correlates with established preeclampsia biomarkers. Circulating EPS8L1 levels mirror biomarker profiles associated with early-onset disease, supporting its candidacy for inclusion in first-trimester screening panels—pending assay standardization and prospective performance data. At present, EPS8L1 is promising but not ready for routine clinical screening.

Hypertensive pregnancy disorders are linked to elevated postpartum cardiovascular risk and long-term morbidity. Placental biomarkers that stratify preeclampsia risk could refine postpartum surveillance and better target cardiovascular prevention. Next steps include prospective assay validation, integration into prenatal screening workflows, and longitudinal linkage of biomarker trajectories to maternal cardiovascular outcomes to operationalize these findings into care pathways.