Clinical evaluation of non-invasive prenatal screening in 32,394 pregnancies from Changzhi Maternal and Child Health Care Hospital of Shanxi China
Abstract
Non-invasive prenatal screening (NIPS)was performed in 32,394 pregnancies, out of which results were available in 32,361 (99.9%) of them.Among the 32,361confirmed samples, 164 cases had positive results and 32197 cases had negative results. Of these positive cases, 116 cases were trisomy 21, 34 cases were trisomy 18 and 14 cases were trisomy 13. No false negative results were found in this cohort. The overall sensitivity and specificity were 100% and 99.91%, respectively. There was no significant difference in test performance between the 7,316 high-risk and 25,045 low-risk pregnancies，(sensitivity, 100% vs 100% (P >0.05); specificity, 99.96% vs 99.95% (P > 0.05)). Factors contributing to false-positive results included fetal CNVs, fetal mosaicism and typically producing Z scores between 3 and 4. Moreover, we analyze NIPT whole-genome sequencing to investigate the Single Nucleotide Polymorphisms (SNPs) associations with drug response or risk of disease. As compare to the 1000g East Asian genome data, the results reveal a significant difference in 7,285,418 SNPs variants of Shanxi pregnant women including 19，293 clinvar recorded variants and 7,266,125 non- clinvar recorded. Our findings showed that NIPS was an effective assay that may be applied as routine screening for fetal trisomies in the prenatal setting. In addition, this study also provides an accurate assessment of significant differencein 7,285,418 SNPs variants in Shanxi pregnant women that were previously unavailable to clinicians in Shanxi population.
References
2. Zhang, H., et al., Statistical Approach to Decreasing the Error Rate of Noninvasive Prenatal Aneuploid Detection caused by Maternal Copy Number Variation. Scientific Reports, 2015. 5(1): p. 16106.
3. Lo, Y.M., et al., Presence of fetal DNA in maternal plasma and serum. Lancet, 1997. 350(9076): p. 485-7.
4. Grace, M.R., et al., Cell-Free DNA Screening: Complexities and Challenges of Clinical Implementation. Obstet Gynecol Surv, 2016. 71(8): p. 477-87.
5. Taglauer, E.S., L. Wilkins-Haug, and D.W. Bianchi, Review: cell-free fetal DNA in the maternal circulation as an indication of placental health and disease. Placenta, 2014. 35 Suppl(Suppl): p. S64-8.
6. Tounta, G., et al., Non-invasive prenatal diagnosis using cell-free fetal nucleic acids in maternal plasma: Progress overview beyond predictive and personalized diagnosis. Epma j, 2011. 2(2): p. 163-71.
7. Barrett, A.N., et al., Measurement of fetal fraction in cell-free DNA from maternal plasma using a panel of insertion/deletion polymorphisms. PLoS One, 2017. 12(10): p. e0186771.
8. Günel, T., et al., Current approaches on non-invasive prenatal diagnosis: Prenatal genomics, transcriptomics, personalized fetal diagnosis. Turk J Obstet Gynecol, 2014. 11(4): p. 233-241.
9. Lee, D.E., et al., Clinical Validation of Non-Invasive Prenatal Testing for Fetal Common Aneuploidies in 1,055 Korean Pregnant Women: a Single Center Experience. J Korean Med Sci, 2019. 34(24): p. e172.
10. Oepkes, D., et al., Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part I-clinical impact. Prenat Diagn, 2016. 36(12): p. 1083-1090.
11. Mei, L., et al., Noninvasive prenatal testing in China: Future detection of rare genetic diseases? Intractable Rare Dis Res, 2014. 3(3): p. 87-90.
12. Hu, H., et al., Clinical Experience of Non-Invasive Prenatal Chromosomal Aneuploidy Testing in 190,277 Patient Samples. Curr Mol Med, 2016. 16(8): p. 759-766.
13. Zhang, X., et al., CUTseq is a versatile method for preparing multiplexed DNA sequencing libraries from low-input samples. Nat Commun, 2019. 10(1): p. 4732.
14. Kim, S., et al., An adaptive detection method for fetal chromosomal aneuploidy using cell-free DNA from 447 Korean women. BMC Medical Genomics, 2016. 9(1): p. 61.
15. Chen, E.Z., et al., Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing. PLoS One, 2011. 6(7): p. e21791.
16. Liang, D., et al., Non-invasive prenatal testing of fetal whole chromosome aneuploidy by massively parallel sequencing. Prenat Diagn, 2013. 33(5): p. 409-15.
17. Yu, D., et al., Noninvasive prenatal testing for fetal subchromosomal copy number variations and chromosomal aneuploidy by low-pass whole-genome sequencing. Mol Genet Genomic Med, 2019. 7(6): p. e674.
18. Qiang, R., et al., Detection of trisomies 13, 18 and 21 using non-invasive prenatal testing. Exp Ther Med, 2017. 13(5): p. 2304-2310.
19. Zhang, H., et al., Non-invasive prenatal testing for trisomies 21, 18 and 13: clinical experience from 146,958 pregnancies. Ultrasound Obstet Gynecol, 2015. 45(5): p. 530-8.
20. Chen, Y., et al., Noninvasive prenatal testing for chromosome aneuploidies and subchromosomal microdeletions/microduplications in a cohort of 42,910 single pregnancies with different clinical features. Hum Genomics, 2019. 13(1): p. 60.
21. Hu, H., et al., Clinical Experience of Non-Invasive Prenatal Chromosomal Aneuploidy Testing in 190,277 Patient Samples. Current Molecular Medicine, 2016. 16(8): p. 759-766.
22. Qi, G., et al., Noninvasive prenatal testing in routine clinical practice for a high-risk population: Experience from a center. Medicine (Baltimore), 2016. 95(41): p. e5126.
23. Hu, H.J., et al., Prospective clinical evaluation of Momguard non-invasive prenatal test in 1011 Korean high-risk pregnant women. J Obstet Gynaecol, 2019: p. 1-6.
24. Bianchi, D.W. and L. Wilkins-Haug, Integration of noninvasive DNA testing for aneuploidy into prenatal care: what has happened since the rubber met the road? Clin Chem, 2014. 60(1): p. 78-87.
25. Sikkema-Raddatz, B., et al., NIPTRIC: an online tool for clinical interpretation of non-invasive prenatal testing (NIPT) results. Sci Rep, 2016. 6: p. 38359.
26. Zhou, X., et al., Contribution of maternal copy number variations to false-positive fetal trisomies detected by noninvasive prenatal testing. Prenat Diagn, 2017. 37(4): p. 318-322.
27. Grati, F.R., Implications of fetoplacental mosaicism on cell-free DNA testing: a review of a common biological phenomenon. Ultrasound Obstet Gynecol, 2016. 48(4): p. 415-423.
28. Dan, S., et al., Clinical application of massively parallel sequencing-based prenatal noninvasive fetal trisomy test for trisomies 21 and 18 in 11,105 pregnancies with mixed risk factors. Prenat Diagn, 2012. 32(13): p. 1225-32.
29. Yu, B., et al., Overall evaluation of the clinical value of prenatal screening for fetal-free DNA in maternal blood. Medicine (Baltimore), 2017. 96(27): p. e7114.
Copyright (c) 2021 WenXia Song, XiaoZe Li, LiHong Wang, ZeRong Yao, FangYing Ruan, ZhiPeng Hu
This work is licensed under a Creative Commons Attribution 4.0 International License.
The published articles will be distributed under the Creative Commons Attribution 4.0 International License (CC BY). It is allowed to copy and redistribute the material in any medium or format, and remix, transform, and build upon it for any purpose, even commercially, as long as appropriate credit is given to the original author(s), a link to the license is provided and it is indicated if changes were made. Users are required to provide full bibliographic description of the original publication (authors, article title, journal title, volume, issue, pages), as well as its DOI code. In electronic publishing, users are also required to link the content with both the original article published in Journal of Medical Biochemistry and the licence used.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.