Noninvasive prenatal test for fetal chromosomal aneuploidies by massively parallel sequencing of cell-free fetal DNA in maternal plasma: The first clinical experience in Korea

Abstract

JGM mostly trisomy 21, relies exclusively on biochemical and sonographic measurements performed in the first and second trimesters. With a 3-5% false-positive rate, first-trimester screening achieves a detection rate of about 60-95% for trisomy 21 [1][2][3]. In 1997, Lo et al. [4] www.e-kjgm.org Purpose: Noninvasive prenatal test (NIPT) by massively parallel sequencing (MPS) of cell-free fetal DNA in maternal plasma marks a significant advancement in prenatal screening, minimizing the need for invasive testing of fetal chromosomal aneuploidies. Here, we report the initial clinical performance of NIPT in Korean pregnant women. Materials and Methods: MPS-based NIPT was performed on 910 cases; 5 mL blood samples were collected and sequenced in the Shenzhen BGI Genomic Laboratory to identify aneuploidies. The risk of fetal aneuploidy was determined by L-score and t-score, and classified as high or low. The NIPT results were validated by karyotyping for the high-risk cases and neonatal follow-up for low-risk cases. Results: NIPT was mainly requested for two clinical indications: abnormal biochemical serum-screening result (54.3%) and advanced maternal age (31.4%). Among 494 cases with abnormal biochemical serum-screening results, NIPT detected only 9 (1.8%) high-risk cases. Sixteen cases (1.8%) of 910 had a high risk for aneuploidy: 8 for trisomy 21, 2 for trisomy 18, 1 for trisomy 13, and 5 for sex chromosome abnormalities. Amniocentesis was performed for 7 of these cases (43.8%). In the karyotyping and neonatal data, no false positive or negative results were observed in our study. Conclusion: MPS-based NIPT detects fetal chromosomal aneuploidies with high accuracy. Introduction of NIPT as into clinical settings could prevent about 98% of unnecessary invasive diagnostic procedures. Key words:Noninvasive prenatal test (NIPT), Cell-free fetal DNA (cffDNA), Fetal chromosomal aneuploidies.86 SH Han, et al. • Noninvasive prenatal test for fetal chromosomal aneuploidies www.e-kjgm.org of circulating cell-free fetal DNA (cffDNA) in maternal plasma, which has opened a new approach to noninvasive prenatal test (NIPT).Since the introduction of NIPT for fetal chromosomal aneuploidies by massively parallel sequencing (MPS), the clinical application of NIPT for screening high-risk pregnant women has grown significantly. Several validation studies of high-risk populations have demonstrated the detection rates for trisomy 21 of >99%, 98% for trisomy 18, and 89% for trisomy 13, with false positive rates of 0.1%, 0.1%, and 0.4%, respectively [5][6][7][8][9][10][11][12][13][14]. Consequently, in high-risk populations, NIPT has been shown to have a higher sensitivity and specificity than biochemical serumscreening tests that are currently in use for these trisomies. Recently, this new approach to fetal aneuploidy screening has been introduced in routine clinical practice [15].The excellent performance of NIPT in multiple clinical validations [5][6][7][8][9][10][11][12][13][14], the noninvasive nature of the testing, and the positi...

Experiences of Prenatal Genetic Screening and Diagnostic Testing Among Pregnant Korean Women of Advanced Maternal Age

“…Kim, 2011). In Korea, noninvasive prenatal testing was first made available in 2012 to pregnant women of advanced age or those who received abnormal biochemical serum screening results (Han et al, 2015). However, invasive diagnostic procedures (e.g., chorionic villus sampling and amniocentesis) are still considered critical diagnostic tests and retain an important role in practice (Papp, 2015; Simpson, 2012).…”