86 Amniotic fluid microRNA profiles in twin-twin transfusion syndrome with and without severe cardiomyopathy

Abstract

Twin-twin transfusion syndrome (TTTS) presents many challenges for clinicians, and the optimal means of identifying which pregnancies will benefit most from intervention is controversial. There is currently no clinically significant biomarker to detect or risk-stratify TTTS. microRNAs (miRs) are small RNAs that regulate gene expression and are biomarkers in various disease processes, including adult and pediatric heart failure. To date no studies have investigated amniotic fluid (AF) miR as a biomarker for severe TTTS. This study aims to assess whether AF miRs could be useful as biomarkers to identify pregnancies at greatest risk of severe cardiomyopathy due to TTTS. AF was collected at the time of amniocentesis or selective fetoscopic laser photocoagulation from monochorionic diamniotic twin pregnancies with TTTS at any stage and stored at -80° C. Fetal echocardiography was available for all subjects, and right ventricular Tei index of the recipient fetus ≥ 0.64 was used to define severe cardiomyopathy. RNA was extracted from the AF samples using the miRNeasy Mini Kit (Qiagen) and miR arrays were performed using the TaqMan Open Array miR panel (ThermoFisher). Student’s t-test was performed between groups and a stringent q-value of <0.005 was used to determine differentially expressed miRs. Hierarchical cluster analysis (HCA) was used to determine if these miRs properly separated the two groups. A total of 11 AF samples from pregnancies with severe cardiomyopathy were compared to 12 control TTTS samples without severe cardiomyopathy. 40 miRs were differentially expressed. HCA (Fig 1) based on these 40 miRs show a strong ability to differentiate the two groups. All differentially expressed miRs were downregulated in the severe cardiomyopathy group with the exception of upregulation of miR-208 (Fig 2), which has previously been shown to be associated with adverse outcomes in dilated cardiomyopathy. AF miRs demonstrate differential expression in TTTS with and without severe cardiomyopathy, and can be an important biomarker of disease severity in this population.View Large Image Figure ViewerDownload Hi-res image Download (PPT)