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

TY - JOUR

T1 - 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?

T2 - A clinical study from Denmark

AU - Hatt, Lotte

AU - Ravn, Katarina

AU - Dahl Jeppesen, Line

AU - Hestbek Nicolaisen, Bolette

AU - Baasch Christensen, Inga

AU - Singh, Ripudaman

AU - Schelde, Palle

AU - Horsholt Thomsen, Simon

AU - Christensen, Rikke

AU - Sinding, Marianne

AU - Vase, Laura

AU - Oestergaard, Marianne

AU - Bender Ruggard, Marie

AU - Jensen, Hanne S

AU - Mogensen, Helle

AU - Uldbjerg, Niels

AU - Becher, Naja

AU - Markholt, Sara

AU - Sandager, Puk

AU - Henning Pedersen, Lars

AU - Vogel, Ida

PY - 2023/6

Y1 - 2023/6

N2 - 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.

AB - 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.

KW - Aneuploidy

KW - Chorionic Villi Sampling

KW - DNA Copy Number Variations

KW - Denmark

KW - Female

KW - Humans

KW - Mosaicism

KW - Pregnancy

KW - Prenatal Diagnosis

KW - Trisomy/diagnosis

UR - http://www.scopus.com/inward/record.url?scp=85160587183&partnerID=8YFLogxK

U2 - 10.1002/pd.6387

DO - 10.1002/pd.6387

M3 - Journal article

C2 - 37199490

SN - 0197-3851

VL - 43

SP - 854

EP - 864

JO - Prenatal Diagnosis

JF - Prenatal Diagnosis

IS - 7

ER -