Clinical utility of prenatal exome sequencing after normal chromosomal microarray in fetuses with structural anomalies

Congenital anomalies detected by ultrasound occur in approximately 2–4% of pregnancies. Cytogenetic testing allows detection of chromosomal abnormalities, but the majority of fetuses remain without a diagnosis. It is in this context that exome sequencing was introduced into prenatal medicine. The objective of this study was to analyze the indications for this test, determine its diagnostic yield, and assess its impact on pregnancy outcome. Among the 68 fetuses included, exome sequencing identified pathogenic variants in 22 cases, corresponding to an overall diagnostic yield of 32%. Termination of pregnancy was requested in 86% of pregnancies with a positive exome result, compared with 35% of those cases with an inconclusive result ( P < 0.001). Nevertheless, in more than half of the cases, the result did not influence the decision to terminate. This study shows that exome sequencing improves the diagnosis of fetal anomalies in prenatal diagnosis and may influence pregnancy outcome. However, in many cases, the decision to terminate pregnancy was made before receiving exome sequencing results, highlighting its mainly diagnostic rather than decisional role.