Performances of noninvasive prenatal detection for fetal chromosome aneuploidy based on Semiconductor Sequencing Platform (SSP) of difference sequencing depths

Abstract Objective：To evaluate the performance of non-invasive prenatal testing (NIPT) for chromosome aneuploidy in different sequencing depths for all chromosome aneuploidies.Methods: A cohort of 61581 pregnancies were recruited to review the results, which contained 49393 cases of NIPT and 12188 cases of NIPT- plus respectively. Cell-free DNA from plasma samples were sequenced by Ion Proton sequencer, with sequencing depths included 0.15X (3 Mb reads) with NIPT and 0.4X (8 Mb reads) with NIPT- plus. All high-risk cases were recommended to undergo invasive prenatal diagnosis, and all pregnant women were followed up.Results: A total of 910 cases were high risk of chromosome aneuploidies predicted by NIPT and NIPT- plus. in which NIPT predicted 682 high risk of chromosome aneuploidies , and NIPT- plus predicted 210, The positive rates were 1.38% and 1.72%, respectively. A total of 811 cases accepted prenatal diagnosis with 627 cases of NIPT and 184 cases of NIPT- plus. The PPV of autosomal aneuploidies in NIPT were 81.99%, 69.23%, 25.00%, 4.55%, respectively. and The PPV of autosomal aneuploidies in NIPT- plus were 86.96%, 80.00%, 35.00%, 8.77%,respectively. The PPV of sex chromosome aneuploidies in NIPT- plus was 50%，which consistent with NIPT. In addition, through follow-up, found 1 cases of false negative with trisomy 18 , both of which was detected by NIPT, and termination of pregnancy after prenatal diagnosis due to ultrasound abnormalities.Conclusion: The PPV of autosomal aneuploidies in NIPT- plus was slightly better than NIPT. It shows that increasing the sequencing depth can improve the detection performance of aneuploidy, which has certain guiding value for clinical application.