Universal chromosomal microarray analysis reveals high proportion of copy number variants in low risk pregnancies.

OBJECTIVES: This study's purpose was to evaluate the yield and utility of routine use of Chromosomal Microarray Analysis (CMA) for prenatal genetic diagnosis in a large cohort of pregnancies with normal Ultrasound (US), termed low risk pregnancies, compared to pregnancies with abnormal US findings, termed high risk pregnancies. METHODS: We reviewed all prenatal CMA results in our center between November 2013 and December 2018. The prevalence of the different CMA results in the Low Risk Pregnancies was compared with CMA results in the high risk pregnancies. Prevalence of the different CMA results in the groups were stratified according to specific indications for testing. We also searched medical records in order to evaluate subsequent US follow-up and the outcome of pregnancies in the low risk pregnancies with clinically significant abnormal CMA results. RESULTS: In a cohort of 6431 CMAs performed in low risk pregnancies the prevalence of clinically significant early onset abnormal CMA results was 1.12% (72/6431), significantly lower than the prevalence in high risk pregnancies (4.98%, 66/1326). Some 0.42% (27/6431) of the low risk pregnancies had pathogenic or likely pathogenic Copy Number Variation (CNV) and another 0.7% (45/6431) had a susceptibility locus with more than 10% penetrance. Follow-up of the pregnancies revealed that 32% (23/72) of pregnancies were terminated when there was a clinically significant early onset CNV. In 17% (12/72) of these pregnancies US abnormalities were discovered later on, after genetic testing was performed. CONCLUSION: Albeit lower than observed in high risk pregnancies, the background risk of identifying an abnormal clinically significant CMA result in pregnancies at a low a priori risk for these findings is substantial, and should be conveyed to all pregnant women. This article is protected by copyright. All rights reserved.