J Genet Med.  2015 Dec;12(2):85-91. 10.5734/JGM.2015.12.2.85.

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

• Han SH
• Yang YH
• Ryu JS
• Kang MS
• Kim YJ
• Lee KR

• KMID: 2149850
• DOI: http://doi.org/10.5734/JGM.2015.12.2.85

Abstract

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.

Keyword

Noninvasive prenatal test (NIPT); Cell-free fetal DNA (cffDNA); Fetal chromosomal aneuploidies

MeSH Terms

Amniocentesis
Aneuploidy*
DNA*
Down Syndrome
Female
Follow-Up Studies
High-Throughput Nucleotide Sequencing*
Humans
Karyotyping
Korea*
Maternal Age
Plasma*
Pregnant Women
Prenatal Diagnosis
Sex Chromosome Aberrations
Trisomy
DNA