898: What have we learned from 691 prenatal Chromosomal microarrays for ventricular septal defects?

Abstract

Ventricular septal defect (VSD) represents the most common type of congenital cardiac disease, affecting more than 1 in 300 live births. The objective of this study was to examine the incidence and nature of abnormal Chromosomal Microarray Analysis (CMA) results in a large cohort of pregnancies with VSD. Data acquisition was performed through Ministry of Health computerized database. All CMA results performed due to VSD during the years 2013-2017 were included. The rate of clinically significant CMA results in subgroups with isolated and non-isolated VSD was compared to two control populations – a systematic review of 9272 pregnancies and a local cohort of 5541 fetuses with normal ultrasound. Overall, 691 CMA analyses performed due to a sonographic indication of VSD were found. Of 568 pregnancies with isolated VSD, 8 (1.4%) clinically significant copy number variants (CNV) were detected (mostly submicroscopic), a non-significant difference compared to low risk pregnancies. Of the 123 pregnancies with non-isolated VSDs, 18 (14.6%) clinically significant CMA results were detected, a considerably increased risk compared to low-risk pregnancies, with a high proportion of karyotype-detectable anomalies (12 of 18 cases, 66.7%). The outcomes of our study, representing the largest number of CMA results in pregnancies with VSD, suggest that the rate of abnormal CMA findings in isolated VSD does not differ from low risk pregnancies. This observation is true for population undergoing routine Down syndrome screening tests and early sonographic evaluation, as well as widely available non-invasive prenatal screening. On the contrary, CMA analysis yields a high detection rate in pregnancies with non-isolated VSD. This issue should further explored by prospective large-scale studies, including the effect of VSD types on fetal genetic testing results.