〔Abstract〕 Objective To explore the application of low depth whole genome sequencing technique combined with karyotype analysis in prenatal diagnosis of high risk pregnant women. Methods Amniocentesis was performed in 165 high-risk pregnant women. The G-banding karyotype of fetal amniotic fluid samples was analyzed while the genomic DNA of fetal amniotic fluid cells was detected by Low-pass whole genome sequencing technology. The sequencing reads were precisely mapped using the human genome(GRCh37, UCSC release hg19) as a reference. Then, the pathogenicity of CNVs was interrogated in ISCA, Decipher, ClinVar and other databases. The differences between G-banded chromosome karyotype analysis and Low-pass whole genome sequencing results were compared. Results Among 165 amniotic fluid samples, 44 cases of trisomy 21, 10 cases of trisomy 18, 1 cases of trisomy 13 were detected by Low-pass whole genome sequencing. The result was consistent with that of G-banding karyotype analysis. In addition, there were 2 cases of sex chromosome abnormality detected by Low-pass whole genome sequencing,1 case more than that detected by G-banding chromosome karyotype analysis,and 10 cases of other types of chromosome abnormality,4 cases more than that detected by G-banding chromosome karyotype analysis. The total detection rate of chromosomal abnormalities by Low-pass whole genome sequencing was 53. 33%,which was 3% higher than that by chromosome G-banding karyotype analysis. Conclusion Low-pass whole genome sequencing has a good application value in prenatal diagnosis of pregnant women with high risk in non-invasive prenatal testing. The combined application of Low-pass whole genome sequencing and G-banding chromosome karyotype analysis can effectively improve the detection rate of chromosome abnormalities in pregnant women with high risk in non-invasive prenatal testing,reduce birth defects and improve population quality.