EP16.14: First trimester screening of circulating C19MC microRNAs and the evaluation of their potential to predict the onset of pre‐eclampsia and IUGR

Abstract

A nested case control study of a longitudinal cohort comparing pregnant women enrolled at 10 to 13 gestational weeks was carried out to evaluate risk assessment for pre-eclampsia and IUGR based on circulating placental specific C19MC microRNAs in early pregnancy. The study was retrospective, designed to run from 2012–2016. The expression of miR-516b-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, and miR-525-5p was determined in plasma samples from pregnancies that subsequently developed pre-eclampsia (21), IUGR (18), and 58 normal pregnancies using real-time PCR and comparative Ct method. 7 patients had symptoms of mild pre-eclampsia and 14 were diagnosed with severe pre-eclampsia. 10 PEP and/or IUGR patients required delivery before 34 weeks of gestation and 29 patients delivered after 34 weeks of gestation. The cerebro-placental ratio (CPR) was below the fifth percentile in 11 IUGR cases. Absent or reversed end-diastolic velocity waveforms in the umbilical artery occurred in 1 IUGR case. Circulating C19MC microRNAs were up-regulated (miR-517-5p, p= 0.005; miR-518b, p= 0.013; miR-520h, p= 0.021) or showed a trend toward up-regulation in patients destined to develop pre-eclampsia (miR-520a-5p, p= 0.067; miR-525-5p, p= 0.073). MiR-517-5p had the best predictive performance for pre-eclampsia with a sensitivity of 42.9%, a specificity of 86.2%, a PPV of 52.9% and a NPV of 80.6%. The combination of all examined circulating C19MC microRNAs had no advantage over using only the miR-517-5p biomarker to predict the occurrence of pre-eclampsia (a sensitivity of 20.6%, a specificity of 90.8%, a PPV of 44.8%, and a NPV of 76.0%). Up-regulation of miR-517-5p, miR-518b and miR-520h was associated with a risk of later development of pre-eclampsia. First trimester screening of extracellular miR-517-5p identified a proportion of women with subsequent pre-eclampsia. No circulating C19MC microRNA biomarkers were identified that could predict later occurrence of IUGR. Supported by PROGRES Q34.