First Trimester Maternal Plasma Aberrant miRNA Expression Associated with Spontaneous Preterm Birth

Abstract

Spontaneous Preterm Delivery (sPTD) is one of the leading causes of perinatal mortality and morbidity worldwide. The present case–control study aims to detect miRNAs differentially expressed in the first trimester maternal plasma with the view to identify predictive biomarkers for sPTD, between 320/7 and 366/7 weeks, that will allow for timely interventions for this serious pregnancy complication. Small RNA sequencing (small RNA-seq) of five samples from women with a subsequent sPTD and their matched controls revealed significant down-regulation of miR-23b-5p and miR-125a-3p in sPTD cases compared to controls, whereas miR-4732-5p was significantly overexpressed. Results were confirmed by qRT-PCR in an independent cohort of 29 sPTD cases and 29 controls. Statistical analysis demonstrated that miR-125a is a promising early predictor for sPTL (AUC: 0.895; 95% CI: 0.814-0.972; p < 0.001), independent of the confounding factors tested, providing a useful basis for the development of a novel non-invasive predictive test to assist clinicians in estimating patient-specific risk.

MicroRNA Associations with Preterm Labor—A Systematic Review

“…Mavreli et al conducted a case-control study to identify differentially expressed miRNAs in first-trimester maternal plasma, aiming to predict spontaneous preterm delivery (sPTD). Specific miRNAs like miR-23b-5p and miR-125a-3p were identified as potential early predictors for sPTD, offering a foundation for non-invasive predictive tests and timely interventions [33].…”

“…Conversely, a significant number of miRNAs have been reported to be significantly downregulated in preterm labor, such as hsa-miR-23b-5p and hsa-miR-125a-3p [33]. This indicates that the reduction in certain miRNAs may also contribute to the initiation of preterm labor.…”

MiRNA‐26a‐5p inhibits preterm labor initiation by targeting and regulating TRPC3 ion channel protein expression

“…38 Many miRNAs are aberrantly expressed in PTB pregnancies, including miR-18a-3p, miR-222-3p, miR-494-3p, miR-98-3p, miR-224-5p, miR-760, miR-143, miR-30e-3p, miR-199b, and miR-125a-3p. [39][40][41][42] Pavlek et al reported that miR-29b was associated with perinatal inflammation in preterm infants. 43 In addition, Peng and co-workers revealed that miR-199a-3p suppressed cervical epithelial cell inflammation by inhibiting the HMGB1/TLR4/NF-κB pathway in PTB.…”

“…MiRNAs exert a critical effect on gene expression as well as various physiological and pathological processes, due to their posttranscriptional regulation through binding to the 3′UTR of target genes 38 . Many miRNAs are aberrantly expressed in PTB pregnancies, including miR‐18a‐3p, miR‐222‐3p, miR‐494‐3p, miR‐98‐3p, miR‐224‐5p, miR‐760, miR‐143, miR‐30e‐3p, miR‐199b, and miR‐125a‐3p 39–42 . Pavlek et al reported that miR‐29b was associated with perinatal inflammation in preterm infants 43 .…”

Pathogenesis of Pregnancy-Related Complications

“…Mavreli et al [ 13 ] introduced miR-125a-3p as a promising early biomarker for prediction of spontaneous preterm birth. Mir-125a-3p was identified as a potential biomarker for the early prediction of spontaneous preterm birth using small RNA-seq and confirmed by qRT-PCR.…”