Abstract:?Objective?To investigate the clinical diagnostic value of low-depth whole genome copy number variation sequencing (CNV-Seq) and karyotype analysis in detecting chromosomal abnormalities associated with fetal growth restriction (FGR) in the second and third trimester of pregnancy.?Methods?Karyotype analysis and CNV-Seq were performed in 138 fetuses who underwent invasive prenatal diagnosis due to FGR during April 2018 and October 2020, and the maternal contamination was eliminated by the combination detection with short tandem repeats (STR).?Results?Among 138 fetuses with FGR, 12 (8.7%, 12/138) with >10 Mb of chromosomal abnormalities were detected by G-banding karyotype analysis. However, only 9 fetuses (6.5%, 9/138) with >10 Mb of chromosomal abnormalities were detected by the CNV-Seq, and 2 with balanced translocation and 1 with low proportion of chimerism were not detected. For the <10 Mb of chromosomal abnormalities, only 1 case was detected by G-banding karyotype analysis, and 11 (8.0%, 11/138) cases were detected by the CNV-seq, including 8 pathogenic CNVs such as 2 cases of Williams-Beuren syndrome, 2 cases of 16p microdeletion / microduplication syndrome, 1 case of Miller-Dieker syndrome, 1 case of wolf-Hirschhorn syndrome, 1 case of 3q29 deletion syndrome and 1 case of paternal uniparental disomy, and 3 variants of uncertain significance (VOUS).?Conclusion?Compared with the traditional G-banding karyotype analysis, CNV-Seq can not only effectively detect the chromosome number and structure abnormalities beyond 10 Mb in prenatal FGR fetuses but also detect the chromosome copy number variations less than 10 Mb in the fetuses with normal chromosome karyotype, which can reveal the genetic causes of prenatal FGR more systematically and comprehensively, and guide the selection of FGR fetuses more scientifically.