OBJECTIVE: The objective of the study was to evaluate risk assessment for gestational hypertension based on the profile of circulating placental specific C19MC microRNAs in early pregnancy. STUDY DESIGN: The prospective longitudinal cohort study of women enrolled at first trimester screening at 10 to 13 weeks was carried out (n = 267). Relative quantification of placental specific C19MC microRNAs (miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525 and miR-526a) was determined in 28 normal pregnancies and 18 pregnancies which developed gestational hypertension using real-time PCR and a comparative Ct method relative to synthetic C. elegans microRNA (cel-miR-39). RESULTS: Increased extracellular C19MC microRNA plasmatic levels (miR-516-5p, p<0.001; miR-517*, p = 0.007; miR-520h, p<0.001; miR-518b, p = 0.002) were detected in patients destined to develop gestational hypertension. MiR-520h had the best predictive performance with a PPV of 84.6% at a 7.1% false positive rate. The combination of miR-520h and miR-518b was able to predict 82.6% of women at the same false positive rate. The overall predictive capacity of single miR-518b (73.3% at 14.3% FPR), miR-516-5p (70.6% at 17.9% FPR) and miR-517* (57.9% at 28.6% FPR) biomarkers was lower. CONCLUSION: The study brought interesting finding that the up-regulation of miR-516-5p, miR-517*, miR-520h and miR-518b is associated with a risk of later development of gestational hypertension. First trimester screening of extracellular miR-520h alone or in combination with miR-518b identified a significant proportion of women with subsequent gestational hypertension.

Clinic of Obstetrics and Gynecology 2nd Faculty of Medicine Charles University 5 Uvalu 84 150 06 Prague Czech Republic

Department of Molecular Biology and Cell Pathology 3rd Faculty of Medicine Charles University Ruska 87 100 00 Prague Czech Republic

Department of Molecular Biology and Cell Pathology 3rd Faculty of Medicine Charles University Ruska 87 100 00 Prague Czech Republic; Institute for the Care of the Mother and Child 3rd Faculty of Medicine Charles University Podolske nabrezi 157 36 147 00 Prague Czech Republic

Institute for the Care of the Mother and Child 3rd Faculty of Medicine Charles University Podolske nabrezi 157 36 147 00 Prague Czech Republic

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The Prediction of Gestational Hypertension, Preeclampsia and Fetal Growth Restriction via the First Trimester Screening of Plasma Exosomal C19MC microRNAs

First trimester screening of circulating C19MC microRNAs and the evaluation of their potential to predict the onset of preeclampsia and IUGR