Introduction: MicroRNAs (miRs) are small RNA molecules, involved in the negative regulation of genes, that are highly stable within the circulation. The FLAG study is a prospective collection of over 2000 maternal blood samples at 28 and 36 weeks gestation. 3.9% of FLAG patients developed preeclampsia(PE) after 36 weeks.
Objectives: We hypothesise that circulating miRs will be dysregulated in the maternal circulation preceding diagnosis of PE. Our objective was to screen women at 36 weeks gestation to identify potential biomarkers of PE.
Methods: A panel of 41 miRs were selected for analysis: 32 were from the placental-specific C19MC cluster and 9 identified as previously associated with PE. A case-control group was selected from the FLAG cohort comprising n=196 controls and n=34 patients destined to develop PE. Whole blood RNA was extracted using PAXgene tubes and a custom qRT-PCR microarray containing 41 miRs and 3 housekeepers used to measure miRs at 36 weeks.
Results: At 36 weeks gestation, miRs 18a, 1283, 16, 149, 363 and 424 were significantly decreased in mothers destined to develop PE (p < 0.0001–0.04). To assess the predictive capacity of miRs, we undertook multivariate logistic regression which identified that miRs 149 and 363 are associated with PE and give the optimum prediction model, with a sensitivity of 45.5% at a specificity of 90%. Assuming the prevalence of PE at 5%, we find a negative predictive value (NPV) of 97%.
Discussion: Whilst the combined sensitivity of miR149 and 363 is low, the reasonable NPV highlights these miRs as potential contributors to a multi-analyte rule-out test at term which could save valuable time and resources. Moreover, these miRs hold potential for the prediction of PE at earlier gestations (if combined with other analytes), a consideration which will be the focus of future work.