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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. [ABSTRACT FROM AUTHOR]

Objective: We aimed to develop cell‐based NIPT for cystic fibrosis (CF) and test a pregnancy at risk of two common pathogenic variants. Method: A pregnant woman carrying monozygotic twins opted for prenatal testing as she and her partner were heterozygote carriers of F508del (c.1521:1523del). The partner was also positive for the CFTR‐related variant R117H (c.350G>A). Fetal trophoblasts from maternal blood were enriched and isolated using antibodies and a capillary‐based cell‐picking instrument. Multiplex PCR‐based fragment length analysis was performed on the extracted fetal DNA for STR‐genotyping, fetal gender and F508del variant status. The R117H variant status was tested using SNaPshot analysis. Results: The fetal origin of the isolated cells was verified by detection of two paternally inherited STR alleles and an Y chromosome marker, while no maternal DNA contamination was detected. The direct variant analysis detected F508del heterozygosity and the SNaPshot analysis for R117H detected only the normal allele. Thus, the results showed that the fetuses were healthy carriers of F508del, concordant with the findings of conventional prenatal testing. Conclusion: Cell‐based NIPT could accurately state the fetal variant status and distinguish fetal trophoblasts from maternal cells. In the future, cell‐based NIPT may provide an accurate less invasive alternative to chorionic villous sampling. [ABSTRACT FROM AUTHOR]