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

Lotte Hatt; Katarina Ravn; Line Dahl Jeppesen; Bolette Hestbek Nicolaisen; Inga Baasch Christensen; Ripudaman Singh; Palle Schelde; Simon Horsholt Thomsen; Rikke Christensen; Marianne Sinding; Laura Vase; Marianne Oestergaard; Marie Bender Ruggard; Hanne S. Jensen; Helle Mogensen; Niels Uldbjerg; Naja Becher; Sara Markholt; Puk Sandager; Lars Henning Pedersen; Ida Vogel

doi:10.1002/pd.6387

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

Lotte Hatt, Katarina Ravn, Line Dahl Jeppesen, Bolette Hestbek Nicolaisen, Inga Baasch Christensen, Ripudaman Singh, Palle Schelde, Simon Horsholt Thomsen, Rikke Christensen, Marianne Sinding, Laura Vase, Marianne Oestergaard, Marie Bender Ruggard, Hanne S. Jensen, Helle Mogensen, Niels Uldbjerg, Naja Becher, Sara Markholt, Puk Sandager, Lars Henning PedersenIda Vogel^*

^*Kontaktforfatter

IRS - Sygehus Lillebælt, Forskningsenhed for Gynækologi og Obstetrik (Kolding)

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Prenatal Diagnosis
Vol/bind	43
Udgave nummer	7
Sider (fra-til)	854-864
ISSN	0197-3851
DOI	https://doi.org/10.1002/pd.6387
Status	Udgivet - jun. 2023

Bibliografisk note

Funding 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.

Publisher Copyright:
© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.

Dokumenter og links

10.1002/pd.6387Licens: CC BY-NC-ND

Open Access VersionForlagets udgivne version, 1,19 MBLicens: CC BY-NC-ND

Citationsformater

Hatt, L., Ravn, K., Dahl Jeppesen, L., Hestbek Nicolaisen, B., Baasch Christensen, I., Singh, R., Schelde, P., Horsholt Thomsen, S., Christensen, R., Sinding, M., Vase, L., Oestergaard, M., Bender Ruggard, M., Jensen, H. S., Mogensen, H., Uldbjerg, N., Becher, N., Markholt, S., Sandager, P., ... Vogel, I. (2023). 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. Prenatal Diagnosis, 43(7), 854-864. https://doi.org/10.1002/pd.6387

@article{b3022029b5e746948f263d4225616af5,

title = "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",

abstract = "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.",

keywords = "Aneuploidy, Chorionic Villi Sampling, DNA Copy Number Variations, Denmark, Female, Humans, Mosaicism, Pregnancy, Prenatal Diagnosis, Trisomy/diagnosis",

author = "Lotte Hatt and Katarina Ravn and {Dahl Jeppesen}, Line and {Hestbek Nicolaisen}, Bolette and {Baasch Christensen}, Inga and Ripudaman Singh and Palle Schelde and {Horsholt Thomsen}, Simon and Rikke Christensen and Marianne Sinding and Laura Vase and Marianne Oestergaard and {Bender Ruggard}, Marie and Jensen, {Hanne S.} and Helle Mogensen and Niels Uldbjerg and Naja Becher and Sara Markholt and Puk Sandager and {Henning Pedersen}, Lars and Ida Vogel",

note = "Funding 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. Publisher Copyright: {\textcopyright} 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.",

year = "2023",

month = jun,

doi = "10.1002/pd.6387",

language = "English",

volume = "43",

pages = "854--864",

journal = "Prenatal Diagnosis",

issn = "0197-3851",

publisher = "Wiley",

number = "7",

}

Hatt, L, Ravn, K, Dahl Jeppesen, L, Hestbek Nicolaisen, B, Baasch Christensen, I, Singh, R, Schelde, P, Horsholt Thomsen, S, Christensen, R, Sinding, M, Vase, L, Oestergaard, M, Bender Ruggard, M, Jensen, HS, Mogensen, H, Uldbjerg, N, Becher, N, Markholt, S, Sandager, P, Henning Pedersen, L & Vogel, I 2023, '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', Prenatal Diagnosis, bind 43, nr. 7, s. 854-864. https://doi.org/10.1002/pd.6387

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. / Hatt, Lotte; Ravn, Katarina; Dahl Jeppesen, Line et al.

I: Prenatal Diagnosis, Bind 43, Nr. 7, 06.2023, s. 854-864.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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

N1 - Funding 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. Publisher Copyright: © 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.

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

U2 - 10.1002/pd.6387

DO - 10.1002/pd.6387

M3 - Journal article

C2 - 37199490

AN - SCOPUS:85160587183

SN - 0197-3851

VL - 43

SP - 854

EP - 864

JO - Prenatal Diagnosis

JF - Prenatal Diagnosis

IS - 7

ER -

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

Abstract

Bibliografisk note

Dokumenter og links

Fingeraftryk

Citationsformater