Small non-coding RNA molecules, called microRNAs (miRNAs), found and measured in the blood plasma of asymptomatic pregnant women may predict development of pre-eclampsia, a condition characterised by high blood pressure and abnormal kidney function that affects roughly 5% to 8% of all pregnancies. Pre-eclampsia is responsible for a significant proportion of maternal and neonatal deaths, low birth weight and is a primary cause of premature birth.
The findings are reported by researchers at University of California – San Diego School of Medicine and Sera Prognostics, Inc, a Salt Lake City-based company that makes diagnostics tests for predicting the risk of premature birth.
"The ability to identify pregnancies at high risk for developing pre-eclampsia would be of great value to patients and their doctors to better personalise prenatal care," said senior author Dr Louise Laurent, professor in the department of obstetrics, gynaecology and Reproductive Sciences at UC San Diego School of Medicine. "This would enable prompt detection and optimal management of pregnancies that develop pre-eclampsia. And the information could be used to better identify participants for research studies testing preventive therapies."
Pre-eclampsia is a common and serious complication of pregnancy. It is estimated to be the cause of 15% of preterm births and 14% of maternal deaths worldwide. Symptoms of pre-eclampsia – most notably hypertension, but also sudden weight gain, swelling, severe headaches, abdominal pain and nausea – appear during the second half of pregnancy, though Laurent said studies suggest the disorder is caused by problems with placental development early in pregnancy.
Delayed diagnosis and suboptimal management of pre-eclampsia typically results in poorer outcomes for mother and child.
The new study involved 141 subjects (49 cases, 92 controls) in the discovery cohort and 71 subjects (24 cases, 47 controls) in a separate verification cohort. Researchers found that two single-miRNA biomarkers (univariate) and 29 two-miRNA (bivariate) biomarkers measured in the serum of asymptomatic pregnant women between 17 and 28 weeks of pregnancy were able to predict later onset of pre-eclampsia.
Laurent said the next step will be to validate these miRNA biomarkers in a large independent pregnancy cohort, with the ultimate goal of developing a clinical test for screening women early in pregnancy for increased risk of pre-eclampsia.
"We look forward to the clinical validation of these novel miRNA biomarkers of pre-eclampsia through our continued collaboration with Laurent and UC San Diego," said Dr Jay Boniface, chief scientific officer at Sera and a study co-author. "Innovative bioinformatics approaches have enabled their discovery and the prospect of creating predictors for individualiSed risk of pregnancy complications."
Abstract
Srinivasan et al. use maternal serum to identify and verify miRNA biomarkers in asymptomatic patients at elevated risk for later development of pre-eclampsia in independent cohorts. Biostatistical analyses show that the verification rate for the reversals using bivariate models is markedly higher than for univariate biomarkers.
Authors
Srimeenakshi Srinivasan, Ryan Treacy, Tiffany Herrero, Richelle Olsen, Trevor R Leonardo, Xuan Zhang, Peter DeHoff, Cuong To, Lara G Poling, Aileen Fernando, Sandra Leon-Garcia, Katharine Knepper, Vy Tran, Morgan Meads, Jennifer Tasarz, Aishwarya Vuppala, Soojin Park, Clara D Laurent, Tony Bui, Pike See Cheah, Rachael Tabitha Overcash, Gladys A Ramos, Hilary Roeder, Ionita Ghiran, Mana Parast, Xandra O Breakefield, Amir J Lueth, Sharon R Rust, Max T Dufford, Angela C Fox, Durlin E Hickok, Julja Burchard, J Jay Boniface, Louise C Laurent, Kim A Boggess, George R Saade, Scott A Sullivan, Glenn R Markenson, Jay D Iams, Dean V Coonrod, Leonardo M Pereira, M Sean Esplin, Larry M Cousins, Garrett K Lam, Matthew K Hoffman
[link url="https://www.sciencedaily.com/releases/2020/05/200519144404.htm"]University of California – San Diego material[/link]
[link url="https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(20)30018-5.pdf"]Cell Reports Medicine abstract[/link]