Identification of circulating placental mRNA in maternal blood of pregnancies affected with fetal congenital heart diseases at the second trimester of pregnancy: implications for early molecular screening

Objective To investigate whether a significantly aberrant expression of circulating placental mRNA genes related with cardiogenesis can be detected at the second trimester of pregnancy. Methods The study was performed in two stages. First stage (development model group): match of 14 placental tissues at delivery of fetuses with congenital heart disease versus 20 controls. Second stage (validation model group): mRNA amplification of abnormal expressed genes in maternal blood samples from 26 women hearing a fetus with a congenital heart disease matched with 28 controls. Results We identified four functional categories of genes possibly involved in abnormal heart development: cardiac morphogenesis: tenascin, thioredoxin, salvador homolog 1 protein; extracellular matrix (ECM) and valvular tissue biosynthesis: placental-associated plasma protein, collagen, type 1, alpha 2, fibulin-1, heparanase. procollagen-proline, 2-oxoglutarate 4-dioxygenase, alpha polypeptide 11, Jumonji, AT rich interactive domain 1B RBP2-like; normal contractile activity: actinin, alpha 4, fascin homolog 1, actin-bundling protein; and congestive heart failure. Conclusion Altered placental genetic expression was found at term delivery in affected fetuses. The aberration was also confirmed in maternal blood at the second trimester of women bearing a fetus with congenital heart disease. Sensitivity for the most aberrant genes ranged between 42% and 95% at a false positive rate (FPR) of 10%. Copyright (C) 2010 John Wiley & Sons, Ltd.