Abstract
To identify maternal serum miRNAs that may be used as antenatal diagnostic markers of abnormal placentation. A multi-site cohort study of maternal serum collected between 14-41 weeks gestational age (GA) from patients with normal and abnormal placentation. Candidate miRNAs were chosen for validation based on analysis of small RNA sequencing data. Validation was performed using Taqman reverse transcription quantitative PCR (RT-qPCR) amplification of each candidate miRNA. Experiments were performed in quadruplicate and medians analyzed. Student’s T test and one-way ANOVA were used to compare means, Pearson’s chi-square test to analyze categorical variables, and linear regression modeling to calculate adjusted significance. Twenty-one candidate miRNAs were selected for RT-qPCR amplification on maternal serum samples from pregnancies with pathology-confirmed diagnosis of placenta accreta spectrum (n = 45), placenta previa (n = 31), and normal controls (n = 50). Multiparity (p < 0.001), race (p < 0.001), BMI (p < 0.001), placental laterality (p = 0.003), GA at blood draw (p < 0.001) were significantly different across the three groups. Analysis of the RT-qPCR Cq values identified miRNA 548av-3p as the strongest candidate to differentiate between accreta and previa (mean Cq 29.11 vs 28.655, p = 0.087). Postulating that bivariate biomarkers of paired miRNA would yield more robust results by providing an internal control, a significant difference was found in the Cq ratio of 548av-3p / 628-3p across the three final diagnoses (p = 0.004), and specifically between accreta vs previa (p = 0.024). After controlling for parity, race, BMI, placenta laterality, and GA at blood draw, the Cq ratio of mi-548av-3p / 628-3p remained a significant predictor for the final diagnosis (partial eta2 = 0.093, p = 0.001). Specific maternal serum miRNAs are differentially expressed among patients with abnormal placentation. These data suggest miRNA 548av-3p may be a potential non-invasive biomarker for antenatal risk assessment of abnormal placentation.View Large Image Figure ViewerDownload Hi-res image Download (PPT)
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