Prenatal evaluation of chromosomal abnormalities and copy number variations in fetuses with single umbilical artery

Abstract

Background A normal umbilical cord has a single umbilical vein and two umbilical arteries. Single umbilical artery (SUA) is one of the most common umbilical anomaly detected by prenatal ultrasonography. The objective of this study was to evaluate the usefulness of copy number variation sequencing (CNV-seq) and standard karyotyping in fetuses with single umbilical artery (SUA) and to investigate the genetic etiology of prenatal SUA. Methods Data from pregnancies referred for invasive testing and copy number variation sequencing (CNV-seq) due to sonographic diagnosis of fetal with SUA from 2013 to 2022 were obtained retrospectively from the computerized database. The rates of chromosome aberrations and abnormal CNV-seq findings for isolated SUA, SUA accompanied with soft markers and ultrasound malformations were calculated. Results Of the 474 fetuses with SUA that underwent karyotyping, chromosomal abnormalities were detected in fetuses, with a chromosomal abnormality rate of 10.3% (49/474). The use of CNV-seq provides a 10.2% (18/177) incremental yield of detecting pathogenic CNVs in fetuses with SUA and normal karyotype. our study showed that the risk of pathogenic chromosomal abnormalities and copy number variations were increased in the SUA combined malformation or soft markers group compared to that in the isolated SUA group.Meanwhile, fetuses with isolated SUA had an additional 3.4% (6/177) of pathogenic CNVs on top of chromosome aneuploidies. Conclusion CNV-seq could aid in the risk assessment and genetic counseling in fetuses with isolated SUA, Integrating CNV analysis and karyotyping for prenatal diagnosis of SUA in prenatal diagnosis can provide more accurate genetic proof for prenatal counseling and prediction of fetal outcomes.