Among different types of congenital heart diseases, ventricular septal defect is the most frequently diagnosed type and is frequently missed in early prenatal screening programs. Herein, we explored the role of maternal serum-derived exosomes in detecting and predicting ventricular septal defect in fetuses in the early stage of pregnancy. A total of 104 pregnant women consisting of 52 ventricular septal defect cases and 52 healthy controls were recruited. TMT/iTRAQ proteomic analysis uncovered 15 maternal serum exosomal proteins, which showed differential expression between ventricular septal defect and control groups. Among these, four down-regulated proteins, lactoferrin, SBSN, DCD, and MBD3, were validated by Western blot. The protein lactoferrin was additionally verified by ELISA which was able to distinguish ventricular septal defects from controls with area under the ROC curve (AUC) 0.804 (p < 0.001). Our findings reveal that lactoferrin in maternal serum-derived exosomes may be a potential biomarker for non-invasive prenatal diagnosis of fetal ventricular septal defects.
Keywords: Ventricular septal defect; biomarker; congenital heart disease; exosomes; prenatal diagnosis.