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First trimester maternal serum MicroRNA expression and pre-eclampsia: a retrospective nested case-control study.
Paula L Hedley1, Severin Olesen Larsen2, Karen R Wøjdemann3
1Department for Congenital Disorders, Statens Serum Institut, Artillerivej 5, Copenhagen, 2300, Denmark. phy@ssi.dk.
BMC Pregnancy and Childbirth
|October 1, 2025
Summary
First-trimester maternal serum microRNAs (miRNAs) can predict pre-eclampsia (PE). Seven specific miRNAs identified can distinguish between healthy pregnancies and those developing PE, aiding early risk assessment.
Area of Science:
- Biochemistry
- Genetics
- Obstetrics
Background:
- Circulating microRNAs (miRNAs) are detectable in maternal blood.
- Previous studies indicated differential miRNA profiles in third-trimester pregnancies with and without pre-eclampsia (PE).
- Early first-trimester studies showed similar differential profiles but were often underpowered.
Purpose of the Study:
- To investigate the potential of first-trimester maternal serum miRNA expression profiles for predicting pre-eclampsia (PE).
- To identify specific miRNAs that can differentiate between uncomplicated pregnancies and those that develop PE.
- To assess the utility of these miRNAs for early PE risk assessment.
Main Methods:
- A nested case-control study involving 413 pregnant women (126 developed PE) with serum samples collected between 10-14 weeks gestation.
- Purification of total RNAs and quantification of 46 selected miRNAs and 2 controls using real-time quantitative PCR.
- Analysis of miRNA expression profiles to identify differentiating markers.
Main Results:
- Seven miRNAs (hsa-miR-181b-5p, -323a-3p, -518b, -363-3p, -20a-5p, -29a-3p, -142-3p) differentiated between uncomplicated pregnancies and those developing PE.
- A single miRNA, hsa-miR-363-3p, distinguished between mild and severe PE.
- A combination of the seven differentiating miRNAs achieved the highest discrimination between PE and uncomplicated pregnancies (AUC = 0.879).
Conclusions:
- First-trimester maternal serum miRNA profiles can effectively differentiate between uncomplicated pregnancies and those complicated by PE.
- These circulating miRNA markers show potential for improving early risk assessment of PE, weeks before symptom onset.
- This finding supports the development of non-invasive biomarkers for predicting PE in early pregnancy.
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