Abstract
ObjectivesA 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 preeclampsia and IUGR based on circulating placental specific C19MC microRNAs in early pregnancy.MethodsThe expression of placental specific C19MC microRNAs (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 preeclampsia (n = 21), IUGR (n = 18), and 58 normal pregnancies using real-time PCR and comparative Ct method relative to synthetic Caenorhabditis elegans microRNA (cel-miR-39).ResultsCirculating 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 preeclampsia (miR-520a-5p, p = 0.067; miR-525-5p, p = 0.073). MiR-517-5p had the best predictive performance for preeclampsia 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 preeclampsia (a sensitivity of 20.6%, a specificity of 90.8%, a PPV of 44.8%, and a NPV of 76.0%).ConclusionsUp-regulation of miR-517-5p, miR-518b and miR-520h was associated with a risk of later development of preeclampsia. First trimester screening of extracellular miR-517-5p identified a proportion of women with subsequent preeclampsia. No circulating C19MC microRNA biomarkers were identified that could predict later occurrence of IUGR.
Highlights
MicroRNAs belong to a family of small noncoding RNAs that regulate gene expression at the post-transcriptional level by degrading or blocking translation of messenger RNA targets [1, 2]
The combination of all examined circulating C19MC microRNAs had no advantage over using only the miR-517-5p biomarker to predict the occurrence of preeclampsia
Prediction of preeclampsia and intrauterine growth restriction (IUGR) via circulating C19MC microRNAs identified a proportion of women with subsequent preeclampsia
Summary
MicroRNAs belong to a family of small noncoding RNAs that regulate gene expression at the post-transcriptional level by degrading or blocking translation of messenger RNA (mRNA) targets [1, 2]. The study by Luque et al [4] demonstrated that maternal serum microRNA assessment at the end of the first trimester of pregnancy did not appear to have any predictive value for early preeclampsia (requiring delivery before 34 weeks), the data from other studies strongly supported the need for a more detailed exploration of microRNAs in maternal circulation with the view toward routine assessment in everyday practice, and recognition that they represent potential biomarkers for pregnancy related complications [5,6,7,8]. Recent studies of Ura et al [5] have shown that severe preeclampsia is associated with alterations in extracellular microRNA expression (miR-1233, miR-520, miR-210 and miR-144) during the early stages of gestation (12–14 weeks)
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