RNA profiles reveal signatures of future health and disease in pregnancy

Maternal morbidity and mortality are rising, with pre-eclampsia a major contributor. The ability to assess underlying pathophysiology before clinical presentation to identify at-risk pregnancies remains elusive. This study demonstrates that plasma cell-free RNA (cfRNA) reveals patterns of normal pregnancy progression and can determine the risk of developing pre-eclampsia months before clinical presentation. Using comprehensive transcriptome data from eight independent prospectively collected cohorts (1,840 pregnancies; 2,539 plasma samples) and retrospective analyses (2,523 pregnancies and samples), the authors show that cfRNA signatures can predict gestational age and pre-eclampsia risk. In a pre-eclampsia dataset (524 samples; 72 cases; 452 non-cases) collected early in pregnancy, cfRNA-based assessment achieved sensitivity and specificity of 82.3% (s.d., 3%), outperforming conventional methods (56.0%, s.d., 9%). cfRNA profiles identify risk through molecular mechanisms common to pre-eclampsia and are independent of clinical variables such as race, BMI, maternal comorbidities, and obstetrical history.

Morten Rasmussen, Mitsu Reddy, Rory Nolan, Joan Camunas-Soler, Arkady Khodursky, Nikolai M. Scheller, David E. Cantonwine, Line Engelbrecht Sørensen, Jia Dai, Arup Dutta, Tiffany Brundage, Faroq Siddiqui, Mainou Thao, Elaine P. S. Gee, Johnny Lai, Courtney Baruch-Gravet, Mark K. Santillán, Sadaf Debs, Shauli M. Amé, Said M. Ali, Melanie Adkins, Mark A. DePistro, Manfred Lee, Eugeni Namsarev, Dorte Jensen (Gybel-Brak), Lillian Skibsted, James A. Licht, Donna A. Santillán, Sunil Sazawal, Rachel M. Tribble, James M. Roberts, Aneesh Jain, Esther Hogdall, Claudia Holzman, Stephen R. Quake, Micheal A. Elovitz, Thomas F. McElrath