Cell-free RNAs in maternal peripheral blood as potential biomarkers of preeclampsia: a review.

Preeclampsia (PE) is a relatively common pregnancy complication that results in significant morbidity and mortality among mothers and children worldwide. It is critical to identify women who are at high risk of developing PE to provide timely treatment, in line with the general shift in medicine towards precision health, with an emphasis on disease prediction and prevention. However, independent and reliable predictors for PE are lacking, and clinical symptoms are typically resolved through delivery. Notably, there have been significant breakthroughs in the use of non-invasive approaches to predict PE, particularly the detection of cell-free RNAs (cfRNAs) in maternal peripheral blood, which are correlated with tissue-specific gene expression and provide a view of prenatal health throughout gestation. Unlike established protein markers such as sFlt-1/PlGF, which primarily reflect angiogenic imbalance and are most informative near the time of clinical presentation, cfRNAs provide a dynamic, tissue-resolved readout of gene expression programs throughout gestation from the placenta, fetus, and maternal organs. Their levels directly correlate with the current state of pregnancy, and cfRNA-based prediction models have demonstrated robust performance, with AUC values ranging from 0.70 to 0.99 and an average sensitivity exceeding 70%. We review recent research on circulating cfRNAs in PE as well as their innovative applications and associated challenges in diagnosing and predicting PE. This review is expected to prompt further research aimed at expanding the clinical applicability of cfRNAs as non-invasive and reliable biomarkers for PE.