Fuman Jiang, Jinghui Ren, Fang Chen, Yuqiu Zhou, Jiansheng Xie, Shan Dan, Yue Su, Jianhong Xie, Baomin Yin, Wen Su, Huakun Zhang, Wei Wang, Xianghua Chai, Linhua Lin, Hui Guo, Qiyun Li, Peipei Li, Yuying Yuan, Xiaoyu Pan, Yihan Li, Lifu Liu, Huifei Chen, Zhaoling Xuan, Shengpei Chen, Chunlei Zhang, Hongyun Zhang, Zhongming Tian, Zhengyu Zhang, Hui Jiang, Lijian Zhao, Weimou Zheng, Songgang Li, Yingrui Li, Jun Wang, Jian Wang, Xiuqing Zhang <<<

Abstract Background Conventional prenatal screening tests, such as maternal serum tests and ultrasound scan, have limited resolution and accuracy. Methods We developed an advanced noninvasive prenatal diagnosis method based on massively parallel sequencing. The Noninvasive Fetal Trisomy (NIFTY) test, combines an optimized Student’s t-test with a locally weighted polynomial regression and binary hypotheses. We applied the NIFTY test to 903 pregnancies and compared the diagnostic results with those of full karyotyping. Results 16 of 16 trisomy 21, 12 of 12 trisomy 18, two of two trisomy 13, three of four 45, X, one of one XYY and two of two XXY abnormalities were correctly identified. But one false positive case of trisomy 18 and one false negative case of 45, X were observed. The test performed with 100% sensitivity and 99.9% specificity for autosomal aneuploidies and 85.7% sensitivity and 99.9% specificity for sex chromosomal aneuploidies. Compared with three previously reported z-score approaches with/without GC-bias removal and with internal control, the NIFTY test was more accurate and robust for the detection of both autosomal and sex chromosomal aneuploidies in fetuses. Conclusion Our study demonstrates a powerful and reliable methodology for noninvasive prenatal diagnosis. <<<