FRI589 MicroRNAs In Maternal Plasma At 15 Weeks Gestation As Biomarkers For Later Preterm Birth: Evidence For Dysregulated Mirna Biogenesis And Implications For Pregnancy-related Endocrine Signaling Pathways

Abstract

Abstract Disclosure: F. Ramzan: None. J. Rong: None. C. Roberts: None. J. O'Sullivan: None. J.K. Perry: None. R. Taylor: None. L. McCowan: None. M.H. Vickers: None. Introduction: Preterm birth (PTB) is a leading cause of morbidity and mortality in infants, with rates of PTB increasing globally over the last 20 years. MicroRNAs (miRNAs) have been reported to have widespread involvement in the development of and protection from many diseases, there is increasing interest in their potential role in the aetiology of a range of pregnancy-related disorders, including PTB. Objectives: To investigate differential miRNA abundances in mid-pregnancy plasma samples between mothers with term infants compared with moderate to late preterm infants (spontaneous PTB) and replication across independent cohorts. Method: The Auckland and Adelaide arms of the Screening for Pregnancy Endpoints (SCOPE) study were utilised. miRNAs in plasma at 15 weeks gestation from mothers of term and moderate to late preterm infants (n=54 per group) were quantified using the NanoString nCounter human v2 miRNA expression panel. Gene expression of key mediators of miRNA biogenesis, including Drosha, Dicer and Argonaut were quantified via RT-qPCR. In-silico analysis was performed to investigate the biological pathways associated with the dysregulated miRNAs. Results: Of the 800 miRNAs examined, the top four miRNAs identified were conserved across both cohorts and were significantly downregulated in the plasma of mothers who later experienced a PTB. The gene pathways associated with the top candidate miRNAs were linked to inflammatory processes, mitochondrial biogenesis, apoptosis and regulation of key pregnancy-related hormonal signaling pathways. Moreover, miRNAs were consistently downregulated in the PTB group concomitant with reduced gene expression of key miRNA biogenesis markers. Conclusions: We identified miRNAs in maternal plasma in mid-pregnancy that were highly predictive of later spontaneous PTB and, importantly, were conserved across two independent cohorts. Moreover, in addition to identifying potential early biomarkers for subsequent PTB, we provide evidence for persistent downregulation of miRNAs in those mothers who later delivered preterm, which is likely to have widespread effects on endocrine signaling pathways during pregnancy. Presentation: Friday, June 16, 2023