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First Trimester Circulating MicroRNA Biomarkers Predictive of Subsequent Preterm Delivery and Cervical Shortening

Authors
  • Cook, Joanna1, 2, 3
  • Bennett, Phillip R.1, 2
  • Kim, Sung Hye1
  • Teoh, Tiong Ghee1, 3
  • Sykes, Lynne1, 2
  • Kindinger, Lindsay M.1, 2, 3
  • Garrett, Alice1
  • Binkhamis, Reem1
  • MacIntyre, David A.1
  • Terzidou, Vasso1, 4
  • 1 Imperial College London, Du Cane Road, Parturition Research Group, Institute of Reproductive and Developmental Biology, London, W12 0NN, UK , London (United Kingdom)
  • 2 Imperial College Healthcare NHS Trust, Du Cane Road, Queen Charlotte’s and Chelsea Hospital, London, W12 0HS, UK , London (United Kingdom)
  • 3 Imperial College Healthcare NHS Trust, St. Mary’s Hospital, Praed Street, London, W2 1NY, UK , London (United Kingdom)
  • 4 Chelsea and Westminster Hospital, Academic Department of Obstetrics and Gynaecology, 369 Fulham Road, London, SW10 9NH, UK , London (United Kingdom)
Type
Published Article
Journal
Scientific Reports
Publisher
Springer Nature
Publication Date
Apr 10, 2019
Volume
9
Issue
1
Identifiers
DOI: 10.1038/s41598-019-42166-1
Source
Springer Nature
License
Green

Abstract

Preterm birth (PTB) is the leading cause of infant death and disability worldwide. The onset of preterm uterine contractions is preceded by asymptomatic cervical remodelling and ripening, which can be seen on trans-vaginal ultrasound as cervical shortening. This study aimed to identify plasma miRNA biomarkers that predict preterm birth and/or cervical shortening. We collected serial plasma samples from pregnant women prospectively from 12 to 22 weeks gestation. The nCounter miRNA assay was used to identify differentially expressed miRNAs associated with spontaneous PTB and/or cervical shortening (n = 16 term no short, n = 13 preterm, n = 24 short). Predictive values of the miRNA biomarkers were confirmed in an independent validation cohort consisting of 96 women who delivered at term, 14 preterm and 21 early cervical shortening at <20 weeks gestation. Nine miRNAs (hsa-let-7a-5p, hsa-miR-374a-5p, hsa-miR-15b-5p, hsa-miR-19b-3p, hsa-miR-23a-3p, hsa-miR-93-5p, hsa-miR-150-5p, hsa-miR-185-5p and hsa-miR-191-5p) were differentially expressed (P < 0.001) in women subsequently experiencing PTB or cervical shortening. Hsa-miR-150-5p had the strongest ability to predict PTB (AUC = 0.8725) and cervical shortening (AUC = 0.8514). Plasma miRNAs in the first trimester can predict PTB and cervical shortening in women at risk of preterm delivery. This is a key period in pregnancy when early identification of PTB risk allows time to deliver outcome-modifying interventions.

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