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. 2025 Oct 1;25(1):995.
doi: 10.1186/s12884-025-08105-x.

First trimester maternal serum MicroRNA expression and pre-eclampsia: a retrospective nested case-control study

Paula L Hedley  1 , Severin Olesen Larsen  2 , Karen R Wøjdemann  3 , Anne-Cathrine Shalmi  4 , Sophie Placing  2 , Line Rode  5 , Anne Cathrine Gjerris  4 , Karin Sundberg  5 , Ann Tabor  5   6 , Michael Christiansen  2   7
Affiliations

First trimester maternal serum MicroRNA expression and pre-eclampsia: a retrospective nested case-control study

Paula L Hedley et al. BMC Pregnancy Childbirth. .

Abstract

Background: 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.

Methods: We conducted a nested case-control study, in which serum samples, taken between 10 and 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.

Results: 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).

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.

Keywords: Circulating MicroRNA; First trimester; Pre-Eclampsia; Quantitative Real-Time PCR.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: 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. Informed consent was obtained from all subjects involved in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Boxplots of delta Cq values for the seven miRNAs determined to have significantly different expression levels between uncomplicated pregnancies and pregnancies which went on to develop PE (mild or severe). Number of samples assessed per group is listed above each box. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001
Fig. 2
Fig. 2
The ROC curve of seven dysregulated miRNAs as well as a combination of all seven. ROC curves are adjusted for maternal weight
See this image and copyright information in PMC

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