Identification of maternal serum microRNAs as novel non-invasive biomarkers for prenatal detection of fetal congenital heart defects

Background: Congenital heart defects (CHD) are the most common form of malformation during embryonic development. Circulating miRNAs have recently been shown to serve as diagnostic/prognostic biomarkers in patients with cancers. Our current study focused on the altered expression of maternal serum miRNAs and their correlation with fetal CHD. Methodology/principle findings: We systematically performed SOLiD sequencing followed by individual quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays to identify and validate the expression of maternal serum miRNAs at 18-22. weeks of gestation. Four miRNAs (miR-19b, miR-22, miR-29c and miR-375) were found to be significantly up-regulated in pregnant women with fetal CHD, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.79, 0.671, 0.767 and 0.693, respectively. Furthermore, the combination of the four miRNAs using multiple logistic regression analysis showed a larger AUC (0.813) that was more efficient for the early detection of fetal CHD. Conclusions/significance: We identified and validated a class of four maternal serum miRNAs which could act as novel non-invasive biomarkers for the prenatal detection of fetal CHD.