The Efficiency Analysis Of High-throughput Sequencing And Standard Prenatal Screening For Detecting Fetal Chromosomal Abnormality

Background:Chromosome disease is one of the most common causes of congenital birth defects, often characterized by multiple malformations, mental retardation, developmental delays and other serious abnormalities with no effective treatment. After prenatal screening, prenatal diagnosis and determining fetal chromosome disease, selective termination of pregnancy with genetic abnormalities is the only effective countermeasures. In the past 30 years, the routine prenatal screening, based on a combination of maternal age, maternal serum biomarkers and fetal ultrasonographic findings, has been the main prenatal screening method. Although standard prenatal screening technology is simple, low prices, and widely promoted, the technology with high rate of false positives and low rate of detection rate of fetal chromosomal abnormalities, has been the main drawback which has trapped the doctors and scientists. In the recent years, with the progress of molecular biology and bioinformatics, the emergence of high-throughput sequencing technology has attracted more and more attention. By extracting free DNA in maternal blood for large-scale sequencing and interpreting the maternal-fetal DNA ratio, HTS has offered us a new choice for prenatal screening. However, there are a lot of controversy between the regular prenatal screening and HTS prenatal screening. So comparing screening efficiency of those two prenatal screening methods for detection of fetal chromosomal abnormalities is the important task for the medical workers.Objective:To evaluate the efficiencies of HTS and standard prenatal screening for detection of fetal chromosome abnormalities.Methods:Standard prenatal screening is based on a combination of maternal age, maternal serum biomarkers and fetal ultrasonographic findings. HTS is based on analysis of cell-free DNA in maternal plasma. The efficiencies of the two screening methods to detect fetal chromosomal abnormalities were compared.Results:6623 were indicated a high risk of aneuploidy in 207689 cases screened by standard prenatal screening,4614 of which were accepted amniocentesis or cordocentesis for prenatal diagnosis.131 cases of fetal chromosomal abnormalities were detected by amniotic fluid/umbilical cord karyotype analysis (2.84%, false positive rate 97.16%). And in 201066 low risk cases,23 cases of chromosome abnormalities were found in the Birth Records System in Hangzhou (0.01%, false negative rate 14.94%).55 were indicated a high risk of aneuploidy in 5579 cases screened by HTS, of which 33 cases of fetal chromosomal abnormalities were detected by amniotic fluid/umbilical cord karyotype analysis (60%, false positive rate 40%). In 5524 low risk cases no fetal chromosome abnormality was found in the Birth Records System (0%, false negative rate 0%). The differences of the efficiencies for detecting fetal chromosome abnormality through those two methods were statistically significant.Conclusion:Compared with standard prenatal screening, the efficiency of HTS for detection of fetal chromosomal abnormalities is much higher. Application of HTS as a routing prenatal screening technology would significantly reduce the case number for prenatal operations resulted by obviously decreased false positives and significantly improve the efficiency of prenatal diagnosis.