OJGen  Vol.8 No.3 , September 2018
Noninvasive Prenatal Testing for Fetal Chromosomal Abnormalities Using Massively Parallel Sequencing: Clinical Experience from 7910 Korean Pregnancies
Abstract: Objective: The purpose of this study is to review the clinical experience and performance of noninvasive prenatal testing (NIPT) method, using cell-free DNAto detect chromosomes 21, 18, 13, X, and Y abnormalities in over 7910 clinical samples from South Korean population. Method: Pregnant women between 1st of November 2015 to 18th of February 2018, with obstetric clinical findings participated in the study. NIPT was performed based on masivelly parallel sequencing with 0.3× low coverage paired-end sequencing using cell-free DNA in maternal plasma. Further invasive prenatal testing was recommended for pregnant women with positive NIPT results. Results: Of the total 7910 participants, 7890 (99.75%) were tested for NIPT and the remaining 20 (0.25%) were below the Quality Control (QC) standards. T13, T18, XXX, XXY and XYY had 100% of sensitivity, specificity, positive predictive values (PPV) and accuracy. The overall sensitivity was 100% and specificity, PPV and accuracy of all chromosomal abnormalities with further validation were 99.92%, 94.25%, and, 99.92% respectively. Conclusion: Our NIPT results showed high positive predictive value for the detection of autosomal trisomies and sex chromosome aneuploidies in our sample cohort.
Cite this paper: Yun, S. , Kwon, H. , Goyal, A. , Shashank, K. , Im, H. , Joo, J. , Bae, J. , Lee, M. and Lee, S. (2018) Noninvasive Prenatal Testing for Fetal Chromosomal Abnormalities Using Massively Parallel Sequencing: Clinical Experience from 7910 Korean Pregnancies. Open Journal of Genetics, 8, 42-53. doi: 10.4236/ojgen.2018.83005.

[1]   Savva, G.M., Morris, J.K., Mutton, D.E. and Alberman, E. (2006) Maternal Age-Specific Fetal Loss Rates in Down Syndrome Pregnancies. Prenatal Diagnosis, 26, 499-504.

[2]   Morris, J.K., Mutton, D.E. and Alberman, E. (2002) Revised Estimates of the Maternal Age Specific Live Birth Prevalence of Down’s Syndrome. Journal of Medical Screening, 9, 2-6.

[3]   Haddow, J.E. (1990) Prenatal Screening for Open Neural Tube Defects, Down’s Syndrome, and Other Major Fetal Disorders. Seminars in Perinatology, 14, 488-503.

[4]   Fairbrother, G., Johnson, S., Musci, T.J. and Song, K. (2013) Clinical Experience of Noninvasive Prenatal Testing with Cell-Free DNA for Fetal Trisomies 21, 18, and 13, in a General Screening Population. Prenatal Diagnosis, 33, 580-583.

[5]   Manotaya, S., Xu, H., et al. (016) Clinical Experience from Thailand: Noninvasive Prenatal Testing as Screening Tests for Trisomies 21, 18 and 13 in 4736 Pregnancies. Prenatal Diagnosis, 36, 224-231.

[6]   Taneja, P.A., Snyder, H.L., et al. (2015) Noninvasive Prenatal Testing in the General Obstetric Population: Clinical Performance and Counseling Considerations in over 35000 Cases. Prenatal Diagnosis, 36, 237-243.

[7]   Fan, H.C., Blumenfeld, Y.J., Chitkara, U., Hudgins, L. and Quake, S.R. (2008) Noninvasive Diagnosis of Fetal Aneuploidy by Shotgun Sequencing DNA from Maternal Blood. Proceedings of the National Academy of Sciences of the United States of America, 105, 16266-16271.

[8]   Kwon, H.J., Goyal, A., et al. (2017) Multiple z-Score Based Method for Noninvasive Prenatal Test Using Cell-Free DNA in Maternal Plasma. Open Journal of Genetics, 7, 1-8.

[9]   Chan, K.C., Zhang, J., Hui, A.B., Wong, N., Lau, T.K., Leung, T.N., Lo, K.W., Huang, D.W. and Lo, Y.M. (2004) Size Distributions of Maternal and Fetal DNA in Maternalplasma. Clinical Chemistry, 50, 88-92.

[10]   Mangs, A.H. and Morris, B.J. (2007) The Human Pseudoautosomal Region (PAR): Origin, Function and Future. Current Genomics, 8, 129-136.

[11]   Skaletsky, H., Kuroda-Kawaguchi, T., Minx, P.J., Cordum, H.S., Hillier, L., Brown, L.G., et al. (2003) The Male-Specific Region of the Human Y Chromosome Is a Mosaic of Discrete Sequence Classes. Nature, 423, 825-837.

[12]   Wang, E., Batey, A., Struble, C., Musci, T., Song, K. and Oliphant, A. (2013) Gestational Age and Maternal Weight Effects on Fetal Cell-Free DNA in Maternal Plasma. Prenatal Diagnosis, 33, 662-666.