Summary
This multi-cohort study demonstrates that plasma cell-free RNA signatures can predict pre-eclampsia risk months before clinical presentation with superior performance to existing methods, whilst remaining independent of conventional clinical risk factors such as maternal age, body mass index and race. The cfRNA signatures reflect underlying placental, maternal and fetal pathophysiology and contain gene features linked to the biological mechanisms of pre-eclampsia. The findings suggest cfRNA profiling could enable early identification of at-risk pregnancies for intervention.
UK applicability
The methodology is potentially applicable to UK maternity services, where pre-eclampsia remains a significant cause of maternal morbidity and mortality. Validation in UK pregnant populations and integration into antenatal screening pathways would be required before clinical adoption.
Key measures
cfRNA transcriptome signatures; sensitivity (75%); positive predictive value (32.3%); model variance explained by clinical factors (less than 1%); time to delivery (14.5 weeks)
Outcomes reported
The study measured cell-free RNA (cfRNA) signatures in maternal blood plasma across eight prospective cohorts (1,840 pregnancies) and retrospective analysis (2,539 samples) to identify patterns of normal pregnancy progression and predict pre-eclampsia risk. cfRNA signatures achieved 75% sensitivity and 32.3% positive predictive value for pre-eclampsia prediction up to 14.5 weeks before clinical presentation.
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