Objective To report the performance of massively parallel sequencing (MPS) based prenatal noninvasive fetal trisomy test based on cell-free DNA sequencing from maternal plasma in a routine clinical setting in China. MethodThe MPS-based test was offered as a prenatal screening test for trisomies 21 and 18 to pregnant women in 49 medical centers over 2 years. A total of 11 263 participants were recruited and the MPS-based test was performed in 11 105 pregnancies. Fetal outcome data were obtained after the expected date of confinement.Results One hundred ninety cases were classified as positive, including 143 cases of trisomy 21 and 47 cases of trisomy 18.With the karyotyping results and the feedback of fetal outcome data, we observed one false positive case of trisomy 21, one false positive case of trisomy 18 and no false negative cases, indicating 100% sensitivity and 99.96% specificity for the detection of trisomies 21 and 18.Conclusion Our large-scale multicenter study proved that the MPS-based test is of high sensitivity and specificity in

BackgroundConventional prenatal screening tests, such as maternal serum tests and ultrasound scan, have limited resolution and accuracy.MethodsWe 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.Results16 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.ConclusionOur study demonstrates a powerful and reliable methodology for noninvasive prenatal diagnosis.

Purpose: To assess the overall diagnostic accuracy of whole-body magnetic resonance imaging (WB-MRI) in detecting bone metastases with a meta-analysis. Materials and Methods:The MEDLINE, EMBASE, Cancerlit, and Cochrane Library databases were searched from January 1995 to September 2010 for studies evaluating the accuracy of WB-MRI in detecting bone metastases. Histopathologic analysis and/or close clinical and imaging follow-up for at least 6 months was assessed. Meta-analysis methods were used to pool sensitivity and specificity and to construct summary receiver-operating characteristics.Results: A total of 11 studies with 495 patients who fulfilled all of the inclusion criteria were considered for the analysis. No publication bias was found. WB-MRI had a pooled sensitivity of 0.899 (95% confidence interval [CI], 0.845-0.939) and a pooled specificity of 0.918 (95% CI, 0.882-0.946). The subgroup without diffusion-weighted imaging (DWI) positive results had higher pooled specificity 0.961 (95% CI, 0.922-0.984) than the subgroup with DWI (P < 0.05).Conclusion: WB-MRI was an accurate, cost-effective tool in detecting bone metastases. WB-MRI without DWI may improve the specificity of detecting bone metastases. DWI seems to be a sensitive but rather unspecific modality for the detection of bone metastatic disease. High-quality prospective studies regarding WB-MRI in detecting bone metastases still need to be conducted.

ObjectivesThe aim of this study was to assess the performance of noninvasively prenatal testing (NIPT) for fetal copy number variants (CNVs) in clinical samples, using a whole-genome sequencing method.MethodA total of 919 archived maternal plasma samples with karyotyping/microarray results, including 33 CNVs samples and 886 normal samples from September 1, 2011 to May 31, 2013, were enrolled in this study. The samples were randomly rearranged and blindly sequenced by low-coverage (about 7M reads) whole-genome sequencing of plasma DNA. Fetal CNVs were detected by Fetal Copy-number Analysis through Maternal Plasma Sequencing (FCAPS) to compare to the karyotyping/microarray results. Sensitivity, specificity and were evaluated.Results33 samples with deletions/duplications ranging from 1 to 129 Mb were detected with the consistent CNV size and location to karyotyping/microarray results in the study. Ten false positive results and two false negative results were obtained. The sensitivity and specificity of detection deletions/duplications were 84.21% and 98.42%, respectively.ConclusionWhole-genome sequencing-based NIPT has high performance in detecting genome-wide CNVs, in particular >10Mb CNVs using the current FCAPS algorithm. It is possible to implement the current method in NIPT to prenatally screening for fetal CNVs.