Maternal plasma is a source of circulating placental nucleic acids. In this study, we validated previous observations on abnormal levels of circulating messenger RNA (mRNA) for the tenascin-X gene in pregnancies with ventricular septal defects in the second trimester of pregnancy.

Objective Maternal plasma is a source of circulating placental nucleic acids. This study was designed to detect aberrantly expressed placental mRNA genes circulating in the maternal plasma of pregnancies affected with fetal conotruncal anomalies (CNTRA) and left-ventricular outflow tract (LVOT) obstruction in the second trimester of pregnancy. Methods This was a retrospective monocentric study conducted from 1 Jan 2016 to 31 Dec 2016. NanoString technology was used to identify aberrantly expressed genes, comparing 36 women carrying a fetus with CNTRA or LVOT obstruction to 42 controls at 19-24 weeks of gestation. The genes with differential expression were subsequently tested using real-time polymerase chain reaction. Linear discriminant analysis was used to combine all the mRNA species with discriminant ability for CNTRA and LVOT obstruction. A multivariable receiver operating characteristic (ROC) curve having the estimated discriminant score as an explanatory variable was generated for the two affected groups versus controls. Results Three genes with differential expression, namely MAPK1, IQGAP1 and Visfatin were found. The ROC curves yielded detection rates of 60 and 62.5% at a false-positive rate of 5% for CNTRA and LVOT, respectively. Conclusions These data suggested that molecular screening of CNTRA and LVOT obstruction in the second trimester is feasible. Prospective studies are needed to test the discriminant ability of these genes and to calculate the predictive positive value in the general population.

ObjectiveTo verify the hypothesis that aberrant placental mRNA genes related to cardiogenesis can be detected in maternal plasma at the second trimester of pregnancy.MethodsNanoString technology was used to identify aberrant genes, comparing 39 women carrying a fetus with a congenital heart defect (CHD) to 31 controls at 19-24weeks of gestation. The genes with differential expression were subsequently tested using real time polymerase chain reaction. Linear discriminant analysis (LDA) was used to combine all the mRNA species with discriminant ability for CHD. A multivariable receiver operating characteristic (ROC) curve having the estimated discriminant score as an explanatory variable was generated.ResultsSix genes with differential expression, namely FALZ, PAPP-A, PRKACB, SAV1, STK4 and TNXB2, were found. The ROC curve yielded a detection rate of 66.7% at a false positive rate of 10%. A higher discriminant score (>75(th) centile) was reached for 14 CHD cases (82.4%) and only 1 control (5.8%). Two cases (11.8%) of heart rhythm disorders also yielded a discriminant score value >75(th) centile.ConclusionThese data represent a step forward in the screening of CHDs. Additional studies are needed to detect more mRNAs with discriminant ability and to move the first trimester screening.