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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement We gratefully acknowledge the financial support to the Copenhagen First Trimester Screening Study from The Danish Medical Research Council, Copenhagen University, The John and Birthe Meyer Foundation, The Ivan Nielsen Foundation, The Hede Nielsen Foundation, The Else and Mogens Wedell-Wedellsborg Foundation, The Dagmar Marshall Foundation, The Egmont Foundation, The Fetal Medicine Foundation, The Augustinus Foundation, The Gangsted Foundation, The A.P.Moeller Foundation, The Mads Clausens Foundation and Copenhagen Hospital Corporation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Copenhagen First Trimester Screening study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Scientific ethics committee of the cities of Copenhagen and Frederiksberg (No. (KF) 01-288/97) and the Data Protection Agency. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data are not publicly available to preserve the privacy of participants under the European General Data Protection Regulation.