Electric Field-Induced Release and Measurement Liquid Biopsy of Urinary Transcriptomics and Key Proteins from Normal...

Noninvasive early detection of patients at the highest risk for the development of adverse pregnancy outcomes (APOs) such as gestational diabetes mellitus (GDM), pre-eclampsia (PE) and gestational hypertension (gHTN) remains a major challenge. Current screening approaches, including maternal blood tests and ultrasound, are limited by either cost, invasiveness, need for specialized skills, or insufficient predictive accuracy. We tested the hypothesis that a novel liquid biopsy approach using Electric Field-Induced Release and Measurement (EFIRM) platform will detect urinary transcripts/proteins in early gestation differentiating patients for the prediction of subsequently developing APOs. In a small prospective study, urine collected temporally from consented pregnant subjects who later developed GDM (n = 12), PE (n = 12), or gHTN (n = 11), were compared to subjects who never developed APOs (Controls [CON], n = 15). Isolated cell-free RNA, subjected to gold standard RNA-sequencing with differential abundances were assessed (both p-adjusted and p-values), and identified early transcriptomic signatures of these APOs. Using EFIRM-derived transcripts we validated these candidate genes and assessed corresponding protein signals. We next developed logistic regression models with leave-one-out cross-validation to preliminarily predict specific APOs. A panel of urinary transcripts (IL1A, MAPK7, TSNARE1) predicted GDM (AUC = 0.96; sensitivity = 0.95, specificity = 0.62, and NPV = 0.95), while a separate panel (NPIPB4, GSDMD, HLA-DPB1) predicted PE (area under the curve [AUC] = 0.92; sensitivity = 0.91, specificity = 0.62, and negative predictive value [NPV] = 0.90), both being distinct from gHTN. These results support the potential of EFIRM as a noninvasive, real-time, multiplexed urine liquid biopsy platform for early screening and monitoring of APOs, suggesting its future utility in prenatal care at an early gestational age.