236: Micro RNA expression profile in pregnant women complicated fetuses with muscular ventricular septal defects

Abstract

Ventricular septal defects (VSD) account for 20% of congenital heart defects (CHDs) and the pathogenesis and molecular mechanism have not been elucidated. MicroRNAs (miRs) are small single-stranded, non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Recent research demonstrated that miRs help regulate embryonic cardiac development, cardiac mophogenesis, and cardiomyocyte growth and differentiation and are closely related to the occurrence of CHDs. This study aimed to measure differences in miR expression in maternal serum in patients complicated with fetal muscular VSD. This was a prospective study including fetuses at risk for CHD (pregestational diabetes, anticonvulsant use, or history of cardiac defects) during 2nd trimester echocardiographic examination. Fetuses without cardiac abnormalities were marked as control. Fetuses with isolated mVSD were marked as abnormal. Maternal venous serum was collected, RNA extracted, and an expression profile of 797 human miRs was measured using NanoString nCounter technology as counts (molecules/100ng RNA). Expression levels of >2fold increase or <50% decrease compared to control were considered up- or downregulated, respectively. Placental-derived miRs within the entire expression profile were also evaluated separately. miRs profiling was obtained in 6 controls and 7 mVSDs cases. Expression levels ranged from 3-198 counts, indicating relatively low expression. The median count did not vary between normal (20.7) and mVSD (21.4). Of the 797, 12 miRs were significantly upregulated (Fig. 1) and 36 miRs downregulated (P<0.01 for both). There were no differences in expression among the 114 known placentally-derived miRs between groups. This study identifies a select serum miR expression profile in women with mVSD fetuses in the 2nd trimester that differs from women with normal fetuses. This approach may provide a quantitative screening tool for confirming fetal CHDs diagnosed by echocardiography. This will be valuable as a biomarker approach for early detection of fetal CHDs in the first trimester to aid diagnosis by fetal echocardiography.