microRNA signatures associated with fetal growth restriction: a systematic review

Placental-origin microRNA (miRNA) profiles can be useful toward early diagnosis and management of fetal growth restriction (FGR) and associated complications. We conducted a systematic review to identify case-control studies that have examined miRNA signatures associated with human FGR. We systematically searched PubMed and ScienceDirect databases for relevant articles and manually searched reference lists of the relevant articles till May 18th, 2021. Of the 2133 studies identified, 21 were included. FGRassociated upregulation of miR-210 and miR-424 and downregulation of a placenta-specific miRNA cluster miRNA located on C19MC (miR-518b, miR-519d) and miR-221-3p was reported by >1 included studies. Analysis of the target genes of these miRNA as well as pathway analysis pointed to the involvement of angiogenesis and growth signaling pathways, such as the phosphatidylinositol 3-kinase- protein kinase B (PI3K-Akt) pathway. Only 3 out of the 21 included studies reported FGR-associated miRNAs in matched placental and maternal blood samples. We conclude that FGR-associated placental miRNAs could be utilized to inform clinical practice towards early diagnosis of FGR, provided enough evidence from studies on matched placental and maternal blood samples become available. Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42019136762.