The objective of reported study was to evaluate the clinical utility of prenatal microarray testing for submicroscopic genomic imbalances in routine prenatal settings and to stratify the findings according to the type of fetal ultrasound anomaly.

From July 2012 to October 2015 chromosomal microarray testing was performed in 218 fetuses with varying indications for invasive prenatal diagnosis: abnormal karyotype, ultrasound anomalies, pathogenic variant in previous pregnancy or carriership in a parent.

The detection rate in the group of fetuses with ultrasound anomalies was 10,0% for pathogenic copy number variants (CNVs), five of them being larger than 8 Mb and expected to be seen on prenatal karyotype. If only those pathogenic CNVs below the classical karyotype resolution are considered, chromosomal microarray testing provided an additional 7,7% diagnostic yield in here reported series. When stratified according to the ultrasound anomalies, the highest percentage of pathogenic CNVs were detected in the group of fetuses with multiple congenital anomalies (16,7%) and lowest in the group of isolated in utero growth restriction (6,3%). In the group of cases with isolated increased nuchal translucency we identified a small interstitial deletion of 16p24.1 involving FOXF1 gene. Prenatal aCGH also provided important insights into cases with seemingly balanced chromosomal rearrangements found on prenatal karyotype, where additional pathogenic CNV were discovered.

Prenatal chromosomal microarray testing significantly increases the diagnostic yield when compared with conventional karyotyping. The highest added value is shown in prenatal diagnostics in fetuses with abnormal ultrasound results. Variants of unknown significance and risk factor CNVs present important challenges and should be discussed with parents in advance, therefore pretest counseling prior to prenatal testing is very important.