Routine use of array comparative genomic hybridization (aCGH) as standard approach for prenatal diagnosis of chromosomal abnormalities. Clinical experience of 1763 prenatal cases

Objective: This study aims to evaluate the diagnostic yield of comparative genomic hybridization microarrays (aCGH) and compare it with conventional karyotype analysis of standard >5-Mb resolution. Method: A total of 1763 prenatal samples were analyzed by aCGH (CytoChip Focus Constitutional microarrays, BlueGnome, Cambridge). The diagnostic yield of chromosomal abnormalities detected by aCGH was assessed, compared with conventional karyotype analysis. Results: The result was pathogenic/unknown penetrance in 125 cases (7.1%), and a variant of unknown significance (VOUS) was detected in 13 cases (0.7%). Out of the 125 cases with abnormal findings, 110 were also detected by conventional karyotype analysis. The aCGH increment in diagnostic yield was 0.9% (15/1763) and 1.6% when VOUS were included. Stratifying the sample according to indications for prenatal invasive testing, the highest values of diagnostic yield increment were observed for patients positive for second-trimester sonographic markers (1.5%) and for the presence of fetal structural anomalies (1.3%). In contrast, the incremental yield was marginal in patients with fetus with increased nuchal translucency (0.5%). Conclusion: The present study indicates that routine implementation of aCGH offers an incremental yield over conventional karyotype analysis, which is also present in cases with 'milder' indications, further supporting its use as a first-tier test. What's already known about this topic? Array CGH has an incremental yield over conventional cytogenetics, which has been mostly highlighted in cases of fetuses with structural defects. What does this study add? The present study is one of the few large cohort studies that support the use of aCGH as a first-tier test for prenatal diagnosis of chromosomal abnormalities, with a significant increase of the incremental diagnostic yield of chromosomal abnormalities. Apart from fetuses with structural defects, an incremental diagnostic yield was also observed for cases with milder indications for invasive testing, for example, second-trimester markers or advanced maternal age, supporting the preferable use of more comprehensive diagnostic approaches in prenatal testing of chromosomal abnormalities.