First trimester maternal serum microRNA expression profile differentiates between uncomplicated pregnancies, and pregnancies which develop pre-eclampsia

Numerous circulating microRNAs (miRNAs) have been detected in maternal blood. Initial studies in third trimester demonstrated differential miRNA expression profiles between uncomplicated pregnancies and pregnancies complicated by pre-eclampsia (PE). Recently, studies in first trimester have shown similar differential profiles, however, these studies were often under-powered. We conducted a nested case-control study, in which serum samples, taken between 10-14 weeks gestation, were obtained from 413 singleton pregnant women, 126 of which later developed PE. Total RNAs were purified and a selection of 46 miRNAs plus two miRNA controls were quantitated by real time quantitative PCR. Seven of the miRNAs, hsa-miR-181b-5p, -323a-3p, -518b, -363-3p, -20a-5p, -29a-3p, and -142-3p, could differentiate between uncomplicated pregnancies and pregnancies which develop PE, but only a single miRNA, hsa-miR-363-3p, could differentiate between mild and severe PE. A combination of all seven differentiating miRNAs was the best at discriminating between PE and uncomplicated pregnancies (AUC= 0.879). In conclusion, first trimester maternal serum miRNA expression profile could differentiate between uncomplicated pregnancies and pregnancies complicated by PE. These circulating miRNA markers have the potential to improve risk assessment of PE in the first trimester, weeks before the onset of symptoms.