Dataset Information

Noninvasive Fetal Trisomy (NIFTY) test: an advanced noninvasive prenatal diagnosis methodology for fetal autosomal and sex chromosomal aneuploidies.

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.

SUBMITTER: Jiang F

PROVIDER: S-EPMC3544640 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Publications

Noninvasive Fetal Trisomy (NIFTY) test: an advanced noninvasive prenatal diagnosis methodology for fetal autosomal and sex chromosomal aneuploidies.

Jiang Fuman F Ren Jinghui J Chen Fang F Zhou Yuqiu Y Xie Jiansheng J Dan Shan S Su Yue Y Xie Jianhong J Yin Baomin B Su Wen W Zhang Huakun H Wang Wei W Chai Xianghua X Lin Linhua L Guo Hui H Li Qiyun Q Li Peipei P Yuan Yuying Y Pan Xiaoyu X Li Yihan Y Liu Lifu L Chen Huifei H Xuan Zhaoling Z Chen Shengpei S Zhang Chunlei C Zhang Hongyun H Tian Zhongming Z Zhang Zhengyu Z Jiang Hui H Zhao Lijian L Zheng Weimou W Li Songgang S Li Yingrui Y Wang Jun J Wang Jian J Zhang Xiuqing X

BMC medical genomics 20121201

<h4>Background</h4>Conventional prenatal screening tests, such as maternal serum tests and ultrasound scan, have limited resolution and accuracy.<h4>Methods</h4>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 wit ...[more]

PMID: 23198897

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Project description:ObjectiveTo assess the detection efficiency of noninvasive prenatal testing (NIPT) for fetal autosomal aneuploidy, sex chromosome aneuploidy (SCA), other chromosome aneuploidy, copy number variation (CNV), and to provide further data for clinical application of NIPT.Materials and methods25,517 pregnant women who underwent NIPT testing in Anhui Province Maternity and Child Health Hospital from September 2019 to September 2020 were selected, and samples with high-risk test results were subjected to karyotype analysis for comparison by using amniotic fluid, with some samples subjected to further validation by chromosomal microarray analysis, and followed up for pregnancy outcome.ResultsA total of 25,517 pregnant women who received NIPT, 25,502 cases were tested successfully, and 294 high-risk samples (1.15%) were detected, there were 96 true positive samples, 117 false positive samples and 81 cases were refused further diagnosis. Samples with high risk of autosomal aneuploidy were detected in 71 cases (0.28%), and 51 cases were confirmed, including: trisomy 21 (T21) in 44 cases, trisomy 18 (T18) in 5 cases, and trisomy 13 (T13) in 2 cases; the positive predictive value (PPV) was 91.67%, 45.45%, and 33.33%, respectively, and the negative predictive value was 100%, the false positive rate (FPR) was 0.02%, 0.02%, and 0.02%, respectively.13 samples with high risk of mosaic trisomies 21, 18, and 13 were detected, and 1 case of T21mos was confirmed with a PPV of 8.33%. Samples with high risk of SCA were detected in 72 cases (0.28%), and the diagnosis was confirmed in 23 cases, with a PPV of 41.07% and a FPR of 0.13%. These included 3 cases of 45,X, 6 cases of 47,XXY, 8 cases of 47,XXX and 6 cases of 47,XYY, with PPVs of 12.00%, 50.00%, 72.73%, and 75.00%, respectively, and false-positive rates of 0.09%, 0.02%, 0.01% and 0.01% respectively. Samples with high risk of CNV were detected in 104 cases (0.41%) and confirmed in 18 cases, with a PPV of 32.14% and a FPR of 0.15%. Samples with high risk of other chromosomal aneuploidy were detected in 34 cases (0.13%), and the diagnosis was confirmed in 3 cases, which were T2, T9, and T16 respectively. The overall PPV for other chromosome aneuploidy was 12.50%, with a FPR of 0.08%.ConclusionNIPT is indicated for trisomies 21, 18 and 13 screening, especially for T21. It also has some certain reference value for SCA and CNV, but is not recommended for screening of other chromosomal aneuploidy.

Project description:BackgroundPregnant people have a risk of carrying a fetus affected by a chromosomal anomaly. Prenatal screening is offered to pregnant people to assess their risk. Noninvasive prenatal testing (NIPT) has been introduced clinically, which uses the presence of circulating cell-free fetal DNA in the maternal blood to quantify the risk of a chromosomal anomaly. At the time of writing, NIPT is publicly funded in Ontario for pregnancies at high risk of a chromosomal anomaly.MethodsWe completed a health technology assessment, which included an evaluation of clinical benefits and harms, value for money, budget impact, and patient preferences related to NIPT. We performed a systematic literature search for studies on NIPT for trisomies 21, 18, and 13, sex chromosome aneuploidies, and microdeletions in the average-risk or general population. We evaluated the cost-effectiveness of traditional prenatal screening, NIPT as a second-tier test (performed after traditional prenatal screening), and NIPT as a first-tier test (performed instead of traditional prenatal screening). We also conducted a budget impact analysis to estimate the additional costs of funding first-tier NIPT. We interviewed people who had lived experience with NIPT and people living with the conditions NIPT screens for, or their families.ResultsThe pooled clinical sensitivity of NIPT in the average-risk or general population was 99.5% (95% confidence interval [CI] 81.8%-99.9%) for trisomy 21, 93.1% (95% CI 75.9%-98.3%) for trisomy 18, and 92.7% (95% CI 81.6%-99.9%) for trisomy 13. The clinical specificity for any trisomy was 99.9% (95% CI 99.8%-99.9%). Compared with traditional prenatal screening, NIPT was more accurate in detecting trisomies 21, 18, and 13, and decreased the need for diagnostic testing. We found limited evidence on NIPT for sex chromosome aneuploidies or microdeletions in the average-risk or general population. Positive NIPT results should be confirmed by diagnostic testing.Compared with traditional prenatal screening, second-tier NIPT detected more affected fetuses, substantially reduced the number of diagnostic tests performed, and slightly reduced the total cost of prenatal screening. Compared with second-tier NIPT, first-tier NIPT detected more affected cases, but also led to more diagnostic tests and additional budget of $35 million per year for average-risk pregnant people in Ontario.People who had undergone NIPT were largely supportive of the test and the benefits of earlier, more accurate results. However, many discussed the need for improved pre- and post-test counselling and raised concerns about the quality of the information they received from health care providers about the conditions NIPT can screen for.ConclusionsNIPT is an effective and safe prenatal screening method for trisomies 21, 18, and 13 in the average-risk or general population. Compared with traditional prenatal screening, second-tier NIPT improved the overall performance of prenatal screening and slightly decreased costs. Compared with second-tier NIPT, first-tier NIPT detected more chromosomal anomalies, but resulted in a considerable increase in the total budget. Interviewees were generally positive about NIPT, but they raised concerns about the lack of good informed-choice conversations with primary care providers and the quality of the information they received from health care providers about chromosomal anomalies.

Dataset Information

Noninvasive Fetal Trisomy (NIFTY) test: an advanced noninvasive prenatal diagnosis methodology for fetal autosomal and sex chromosomal aneuploidies.

Background

Methods

Results

Conclusion

Publications

Noninvasive Fetal Trisomy (NIFTY) test: an advanced noninvasive prenatal diagnosis methodology for fetal autosomal and sex chromosomal aneuploidies.

Similar Datasets

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