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.
Bibliografisk noteFunding Information:
The completion of this study would not have been possible without the support from pregnant women who generously donated a blood sample. We would like to acknowledge the Danish Central Cytogenetics Register. Special thanks to the technicians at the Department of Clinical Genetics, Aarhus University Hospital, for meticulous everyday work. Technician Filiz Kesgin from the Department of Clinical Medicine, Aarhus University, is thanked for her assistance on patient recruitment and blood sampling. We would like to acknowledge the laboratory technicians at ARCEDI for their skills in isolation and genotyping of circulating trophoblasts. The fetal cell isolation and down‐stream analyses by CMA were funded by ARCEDI Biotech. Ida Vogel was supported by a grant from the Novo Nordisk Foundation (NNF16OC0018772). LHP is supported by a Borregaard Clinical Ascending Investigator Grant from the Novo Nordisk Foundation (NNF18OC0054457). Research related to this study at the Department of Obstetrics and Gynecology, Aarhus University Hospital was sponsored by ARCEDI Biotech.
© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.