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Open Access 01-12-2021 | Chromosomal Abnormality | Research article

Cell-free fetal DNA testing and its correlation with prenatal indications

Authors: Jing-wei Wang, Yong-nan Lyu, Bin Qiao, Yan Li, Yan Zhang, Pavan Kumar Dhanyamraju, Yevgeniya Bamme, Michael D. Yu, Dongqin Yang, Yong-qing Tong

Published in: BMC Pregnancy and Childbirth | Issue 1/2021

Abstract

Background

The prenatal test of cell-free fetal DNA (cffDNA) is also known as noninvasive prenatal testing (NIPT) with high sensitivity and specificity. This study is to evaluate the performance of NIPT and its clinical relevance with various clinical indications.

Methods

A retrospective analysis was conducted on 14,316 pregnant women with prenatal indications, including advanced maternal age (≥35 years), maternal serum screening abnormalities, the thickened nuchal translucency (≥2.5 mm) and other ultrasound abnormalities, twin pregnancy/IVF-ET pregnancy, etc. The whole-genome sequencing (WGS) of maternal plasma cffDNA was employed in this study.

Results

A total of 189 (1.32%) positive NIPT cases were identified, and 113/189 (59.79%)cases were confirmed by invasive prenatal testing. Abnormal serological screening (53.14%) was the most common indication, followed by elderly pregnancy (23.02%). The positive prediction value for T21, T18, T13, sex chromosome abnormalities, other autosomal aneuploidy abnormalities, and CNV abnormalities were 91.84, 68.75,37.50, 66.67, 14.29, and 6.45%, respectively. The positive rate and the true positive rate of nuchal translucency (NT) thickening were the highest (4.17 and 3.33%), followed by the voluntary requirement group (3.49 and 1.90%) in the various prenatal screening indications. The cffDNA concentration was linearly correlated with gestational age (≥10 weeks) and the positive NIPT group’s Z-score values.

Conclusions

whole-genome sequencing of cffDNA has extremely high sensitivity and specificity for T21, high sensitivity for T18, sex chromosome abnormalities, and T13. It also provides evidence for other abnormal chromosomal karyotypes (CNV and non-21/18/13 autosomal aneuploidy abnormalities). The cffDNA concentration is closely related to the gestational age and determines the specificity of NIPT. Our results highlight NIPT’s clinical significance, which is an effective prenatal screening tool for high-quality care of pregnancy.

Alberry M, Maddocks D, Jones M, Abdel Hadi M, Abdel-Fattah S, Avent N, Soothill PW. Free fetal DNA in maternal plasma in anembryonic pregnancies: confirmation that the origin is the trophoblast. Prenatal diagnosis. 2007;27:415–8.

Cernat A, De Freitas C, Majid U, Trivedi F, Higgins C, Vanstone M. Facilitating informed choice about non-invasive prenatal testing (NIPT): a systematic review and qualitative meta-synthesis of women’s experiences. BMC Pregnancy Childbirth. 2019;19(1):27. https://doi.org/10.1186/s12884-018-2168-4.CrossRefPubMedPubMedCentral

Pös O, Budiš J, Szemes T. Recent trends in prenatal genetic screening and testing. F1000Res. 2019;8:F1000 Faculty Rev-1764.CrossRef

Bayindir B, Dehaspe L, Brison N, Brady P, Ardui S, Kammoun M, et al. Noninvasive prenatal testing using a novel analysis pipeline to screen for all autosomal fetal aneuploidies improves pregnancy management. Eur J Hum Genet. 2015;23(10):1286–93. https://doi.org/10.1038/ejhg.2014.282.CrossRefPubMedPubMedCentral

Wang Y, Chen Y, Tian F, Zhang J, Song Z, Wu Y, et al. Maternal mosaicism is a significant contributor to discordant sex chromosomal aneuploidies associated with noninvasive prenatal testing. Clin Chem. 2014;60:251–9.CrossRef

Yu T, Li S, Zhao W, Yu D. False positive non-invasive prenatal testing results due to vanishing twins. Chin J Med Genet. 2019;36(4):327–30. https://doi.org/10.3760/cma.j.issn.1003-9406.2019.04.009.CrossRef

Chen EZ, Chiu RWK, Sun H, Akolekar R, Chan KCA, Leung TY, et al. Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing. PLoS One. 2011;6(7):e21791. https://doi.org/10.1371/journal.pone.0021791.CrossRefPubMedPubMedCentral

Jiang F, Ren J, Chen F, Zhou Y, Xie J, Dan S, et al. Noninvasive Fetal Trisomy (NIFTY) test: an advanced noninvasive prenatal diagnosis methodology for fetal autosomal and sex chromosomal aneuploidies. BMC Med Genet. 2012;5(1):57. https://doi.org/10.1186/1755-8794-5-57.CrossRef

Chiu RW, Chan KC, Gao Y, Lau VY, Zheng W, Leung TY, et al. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci U S A. 2008;105(51):20458–63. https://doi.org/10.1073/pnas.0810641105.CrossRefPubMedPubMedCentral

10.

Yin A-h, Peng C-f, Zhao X, Caughey BA, Yang J-x, Liu J, et al. Noninvasive detection of fetal subchromosomal abnormalities by semiconductor sequencing of maternal plasma DNA. Proc Natl Acad Sci U S A. 2015;112:14670–5.CrossRef

11.

Illanes S, Denbow M, Kailasam C, Finning K, Soothill PW. Early detection of cell-free fetal DNA in maternal plasma. Early Hum Dev. 2007;83(9):563–6. https://doi.org/10.1016/j.earlhumdev.2006.11.001.CrossRefPubMed

12.

Gil MM, Accurti V, Santacruz B, Plana MN, Nicolaides KH. Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol. 2017;50:302–14.CrossRef

13.

Taylor-Phillips S, Freeman K, Geppert J, Agbebiyi A, Uthman OA, Madan J, et al. Accuracy of non-invasive prenatal testing using cell-free DNA for detection of down, Edwards and Patau syndromes: a systematic review and meta-analysis. BMJ Open. 2016;6(1):e010002. https://doi.org/10.1136/bmjopen-2015-010002.CrossRefPubMedPubMedCentral

14.

Weiying M, Peng Z, Youqiong L, Yaoxi M, Hongyan Z, Renfeng Z. Application of non-invasive DNA prenatal diagnosis for pregnant women with advanced maternal age. Chin J Clin Obstet Gynecol. 2018;19:541–3.

15.

Ying L, Ping H, Dingyuan M, Fuman J, Xiuqing J, An L, et al. Analysis of the results of non-invasive genetic testing for common fetal chromosomal aneuploidy and genetic counseling. Chin J Med Genet. 2014;31:672–3.

16.

Honglei D, Jie L, Yuan X, Yali H. Clinical indications and detection efficiency of non-invasive prenatal testing in 13 041 cases from Jiangsu. Chin J Perinat Med. 2014;17:813–6.

17.

Tian Y, Zhang L, Tian W, Gao J, Jia L, Cui S. Analysis of the accuracy of Z-scores of non-invasive prenatal testing for fetal Trisomies 13, 18, and 21 that employs the ion proton semiconductor sequencing platform. Mol Cytogenet. 2018;11(1):49. https://doi.org/10.1186/s13039-018-0397-x.CrossRefPubMedPubMedCentral

18.

Wang S, Huang S, Ma L, Liang L, Zhang J, Zhang J, et al. Maternal X chromosome copy number variations are associated with discordant fetal sex chromosome aneuploidies detected by noninvasive prenatal testing. Clin Chim Acta. 2015;444:113–6. https://doi.org/10.1016/j.cca.2015.02.014.CrossRefPubMed

19.

Gil MM, Galeva S, Jani J, Konstantinidou L, Akolekar R, Plana MN, et al. Screening for trisomies by cfDNA testing of maternal blood in twin pregnancy: update of the Fetal Medicine Foundation results and meta-analysis. Ultrasound Obstet Gynecol. 2019;53(6):734–42. https://doi.org/10.1002/uog.20284.CrossRefPubMed

20.

Zhang H, Gao Y, Jiang F, Fu M, Yuan Y, Guo Y, et al. Non-invasive prenatal testing for trisomies 21, 18 and 13: clinical experience from 146 958 pregnancies. Ultrasound Obstet Gynecol. 2015;45:530–8.CrossRef

21.

Bianchi D, Swanson A, Parsa S, Bhatt S, Halks-Miller M, Sehnert A, et al. NIPT for sex chromosome aneuploidy: initial clinical laboratory experience and biologic reasons for discordant results; 2014.

22.

Grati FR. Implications of fetoplacental mosaicism on cell-free DNA testing: a review of a common biological phenomenon. Ultrasound Obstet Gynecol. 2016;48(4):415–23. https://doi.org/10.1002/uog.15975.CrossRefPubMed

23.

Gregg AR, Skotko BG, Benkendorf JL, Monaghan KG, Bajaj K, Best RG, et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2016;18(10):1056–65. https://doi.org/10.1038/gim.2016.97.CrossRefPubMed

24.

Song Y, Huang S, Zhou X, Jiang Y, Qi Q, Bian X, Zhang J, Yan Y, Cram DS, Liu J. Non-invasive prenatal testing for fetal aneuploidies in the first trimester of pregnancy. Ultrasound Obstet Gynecol. 2015;45(1):55–60. https://doi.org/10.1002/uog.13460.

25.

Devers PL, Cronister A, Ormond KE, Facio F, Brasington CK, Flodman P. Noninvasive prenatal testing/noninvasive prenatal diagnosis: the position of the National Society of Genetic Counselors. J Genet Couns. 2013;22(3):291–5. https://doi.org/10.1007/s10897-012-9564-0.CrossRefPubMed

26.

Salomon LJ, Alfirevic Z, Audibert F, Kagan KO, Paladini D, Yeo G, et al. ISUOG consensus statement on the impact of non-invasive prenatal testing (NIPT) on prenatal ultrasound practice. Ultrasound Obstet Gynecol. 2014;44(1):122–3. https://doi.org/10.1002/uog.13393.CrossRefPubMed

27.

Wapner RJ, Babiarz JE, Levy B, Stosic M, Zimmermann B, Sigurjonsson S, et al. Expanding the scope of noninvasive prenatal testing: detection of fetal microdeletion syndromes. Am J Obstet Gynecol. 2015;212:332.e331–9.CrossRef

28.

Jia Y, Zhao H, Shi D, Peng W, Xie L, Wang W, et al. Genetic effects of a 13q31.1 microdeletion detected by noninvasive prenatal testing (NIPT). Int J Clin Exp Pathol. 2014;7(10):7003–11.PubMedPubMedCentral

Title: Cell-free fetal DNA testing and its correlation with prenatal indications
Authors: Jing-wei Wang
Yong-nan Lyu
Bin Qiao
Yan Li
Yan Zhang
Pavan Kumar Dhanyamraju
Yevgeniya Bamme
Michael D. Yu
Dongqin Yang
Yong-qing Tong
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Chromosomal Abnormality
Trisomy 21
Published in: BMC Pregnancy and Childbirth / Issue 1/2021
Electronic ISSN: 1471-2393
DOI: https://doi.org/10.1186/s12884-021-04044-5

2024 ASCO Annual Meeting

Springer Medicine

Cell-free fetal DNA testing and its correlation with prenatal indications

Abstract

Background

Methods

Results

Conclusions

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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