The genetic landscape of copy number variation in a Vietnamese cohort of 5008 fetuses with clinical anomalies during pregnancy

Abstract Copy number variation (CNV) analysis is a powerful tool for discovering structural genomic variation. Still, no program uses this tool to analyze chromosomal aneuploidies in the Vietnamese population. Pregnant women attending routine prenatal checkups in Vietnam from October 2018 to May 2021 were included in this study and contributed fetal tissue to test the utility of CNV analysis for prenatal screening. Among 5,008 women screened, 958 (19.13%) harbored at least one CNV, comprising segmental aneuploidy (8.49%), trisomy (6.91%), multiple anomalies (2.10%), and sex chromosome abnormality (1.64%). The rate of segmental aneuploidy detection increased with gestational age, but trisomy and sex chromosomal abnormalities detection decreased as the pregnancy continued. This study also found an association between abnormal CNVs and several phenotypic markers. For ultrasound soft markers, an increased nuchal fold thickness correlated with a higher risk of abnormal CNVs. In addition, many soft indicators or structural abnormalities were significantly associated with an increased likelihood of abnormal CNVs. This work highlights the importance of CNV analysis for the early detection of prenatal congenital abnormalities, especially in the first trimester. This study’s findings will meaningfully aid policymakers in developing cost-effective genetic prenatal screening programs.