<p>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 (<i>n</i> = 12), PE (<i>n</i> = 12), or gHTN (<i>n</i> = 11), were compared to subjects who never developed APOs (Controls [CON], <i>n</i> = 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 (<i>IL1A, MAPK7, TSNARE1</i>) predicted GDM (AUC = 0.96; sensitivity = 0.95, specificity = 0.62, and NPV = 0.95), while a separate panel (<i>NPIPB4, GSDMD, HLA-DPB1</i>) 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.</p>