Candidate Gene and MicroRNA Expression in Fetal Membranes and Preterm Delivery Risk

We investigated candidate gene and microRNA (miRNA) expression in amnion and chorion in relation to risk of preterm delivery (PTD). Amnion and chorion were separated from placenta and collected at delivery from participants who delivered at term (N = 10) and from participants who delivered preterm following spontaneous labor (sPTL-PTD; N = 10), premature rupture of membranes (PPROM-PTD; N = 10), and preeclampsia (PE-PTD; N = 10). Expression of genes (metalloproteinase [MMP] 2, MMP-9, and tissue inhibitors of MMP-1) and miRNAs (miR-199a*, -202*, -210, -214, -223, and -338) was profiled using quantitative real-time polymerase chain reaction approaches. Adjusted multinomial logistic regression models were used to calculate relative risk ratios (RRR), 95% confidence intervals, and P values. Among controls, the expression of miR-199a*, -202*, and -214 was lower in the amnion compared with their expression in the chorion, whereas the expression of miR-210 was higher in the amnion compared with its expression in the chorion (all P values < .05). In the amnion, MMP-9 expression was associated with PTD risk (overall P value = .0092), and MMP-9 expression was positively associated with the risk of PPROM-PTD (RRR: 31.10) and inversely associated with the risk of PE-PTD (RRR:6.55e-6), although individual associations were not statistically significant. In addition, in the amnion, the expression of miR-210 (RRR: 0.45; overall P value = .0039) was inversely associated with the risk of PE-PTD, and miR-223 was inversely associated with all subtypes of PTD (overall P value = .0400). The amnion and chorion differ in their miRNA expression. The expression of MMP-9, miR-210, and -223 in the amnion is associated with PTD risk.