How does cell‐based non‐invasive prenatal test (NIPT) perform against chorionic villus sampling and cell‐free NIPT in detecting trisomies and copy number variations? A clinical study from Denmark

• Published in: Prenatal diagnosis 2023-06, Vol.43 (7), p.854-864
• Main Authors: Hatt, Lotte, Ravn, Katarina, Dahl Jeppesen, Line, Hestbek Nicolaisen, Bolette, Baasch Christensen, Inga, Singh, Ripudaman, Schelde, Palle, Horsholt Thomsen, Simon, Christensen, Rikke, Sinding, Marianne, Vase, Laura, Oestergaard, Marianne, Bender Ruggard, Marie, Jensen, Hanne S., Mogensen, Helle, Uldbjerg, Niels, Becher, Naja, Markholt, Sara, Sandager, Puk, Henning Pedersen, Lars, Vogel, Ida
• Format: Article
• Language: English
• Subjects: Aberration; Aneuploidy; Chorionic Villi Sampling; Chromosome aberrations; Chromosomes; Copy number; Denmark; DNA Copy Number Variations; Female; Fetuses; Genomes; Humans; Mosaicism; Pregnancy; Prenatal Diagnosis; Sampling; Sex chromosomes; Trisomy - diagnosis; Trisomy - genetics; Trophoblasts; Villus
• ISSN: 0197-3851; 1097-0223
• DOI: 10.1002/pd.6387

Objectives We aimed to compare cell‐based NIPT (cbNIPT) to chorionic villus sampling (CVS) and to examine the test characteristics of cbNIPT in the first clinical validation study of cbNIPT compared to cell‐free NIPT (cfNIPT). Material and Methods Study 1: Women (N = 92) who accepted CVS were recruited for cbNIPT (53 normal and 39 abnormal). Samples were analyzed with chromosomal microarray (CMA). Study 2: Women (N = 282) who accepted cfNIPT were recruited for cbNIPT. cfNIPT was analyzed using sequencing and cbNIPT by CMA. Results Study 1: cbNIPT detected all aberrations (32/32) found in CVS: trisomies 13, 18 and 21 (23/23), pathogenic copy number variations (CNVs) (6/6) and sex chromosome aberrations (3/3). cbNIPT detected 3/8 cases of mosaicism in the placenta. Study 2: cbNIPT detected all trisomies found with cfNIPT (6/6) and had no false positive (0/246). One of the three CNVs called by cbNIPT was confirmed by CVS but was undetected by cfNIPT, two were false positives. cbNIPT detected mosaicism in five samples, of which two were not detected by cfNIPT. cbNIPT failed in 7.8% compared to 2.8% in cfNIPT. Conclusion Circulating trophoblasts in the maternal circulation provide the potential of screening for aneuploidies and pathogenic CNVs covering the entire fetal genome. Key points What is already known about this topic? Circulating fetal trophoblasts can be isolated from maternal circulation and whole genome amplified DNA can be obtained. Case studies have demonstrated its use in detecting aneuploidies, copy number variations (CNVs) and monogenic disorders. What does this study add? This is the first clinical validation study reporting high sensitivity and specificity for aneuploidies and likely also for CNVs over the entire genome. Known microdeletion/duplication syndromes as well as unique disease causing CNVs >1 MB can be reliably detected.