Abstract: Objective：To explore the combined application of single nucleotide polymorphism array (SNP array) and chromosome karyotype analysis in the prenatal diagnosis of pregnant women with different high-risk factors, and to understand the abnormal karyotype detection in different high-risk cases. Methods：A total of 356 pregnant women with high risks were included from January 2016 to June 2018. All of them underwent amniocentesis during the mid trimester of pregnancy. The aminotic cells were used for Karyotype analysis and SNP array. The results of SNP array were compared in the different groups with the high-risk factors including the advanced age, abnormal expression under ultrasound, adverse pregnancy history, chromosomal abnormality of couples, high-risk in serological screening, and two or more high-risk factors. Results：Six aminotic samples were failed to detect. The rate of abnormal chromosome karyotype was 6.29%, while the rate of copy number variation (CNV) in SNP array was 10.57% ( χ2=10.316, P=0.001). Interestingly, there were significant differences in the detection rate of pathogenic CNVs (pCNVs) among those pregnant women with different high-risk factors ( χ2=13.238, P=0.021). Meanwhile, the detection rate of pCNVs in pregnant women with two or more high-risk factors was significantly higher than the rates of pCNVs in other groups, and this rate was also higher than the rate of abnormal karyotype of traditional karyotype analysis ( χ2=4.167, P=0.031). Conclusions：SNP array can greatly increase the detection rate of pCNVs in those pregnant women with high-risk factors, while the application when combined with the routine karyotype analysis can detect the translocations and chimeras of chromosomes complementarily. This strategy can reduce the missed diagnosis and birth defects. We believe that SNP array can be used as the first choice of prenatal diagnosis in those pregnant women with two or more high-risk factors.

Key words: Chromosome microarray analysis, Polymorphism, single nucleotide, Karyotype analysis, High-risk women, Prenatal diagnosis