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Validation of a Single-Nucleotide Polymorphism-Based Non-Invasive Prenatal Test in Twin Gestations: Determination of Zygosity, Individual Fetal Sex, and Fetal Aneuploidy

We analyzed maternal plasma cell-free DNA samples from twin pregnancies in a prospective blinded study to validate a single-nucleotide polymorphism (SNP)-based non-invasive prenatal test (NIPT) for zygosity, fetal sex, and aneuploidy. Zygosity was evaluated by looking for either one or two fetal gen...

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Autores principales: Norwitz, Errol R., McNeill, Gabriel, Kalyan, Akshita, Rivers, Elizabeth, Ahmed, Ebad, Meng, Ling, Vu, Phikhanh, Egbert, Melissa, Shapira, Marlene, Kobara, Katie, Parmar, Sheetal, Goel, Shruti, Prins, Sarah A., Aruh, Israel, Persico, Nicola, Robins, Jared C., Kirshon, Brian, Demko, Zachary P., Ryan, Allison, Billings, Paul R., Rabinowitz, Matthew, Benn, Peter, Martin, Kimberly A., Hedriana, Herman L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679081/
https://www.ncbi.nlm.nih.gov/pubmed/31261782
http://dx.doi.org/10.3390/jcm8070937
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author Norwitz, Errol R.
McNeill, Gabriel
Kalyan, Akshita
Rivers, Elizabeth
Ahmed, Ebad
Meng, Ling
Vu, Phikhanh
Egbert, Melissa
Shapira, Marlene
Kobara, Katie
Parmar, Sheetal
Goel, Shruti
Prins, Sarah A.
Aruh, Israel
Persico, Nicola
Robins, Jared C.
Kirshon, Brian
Demko, Zachary P.
Ryan, Allison
Billings, Paul R.
Rabinowitz, Matthew
Benn, Peter
Martin, Kimberly A.
Hedriana, Herman L.
author_facet Norwitz, Errol R.
McNeill, Gabriel
Kalyan, Akshita
Rivers, Elizabeth
Ahmed, Ebad
Meng, Ling
Vu, Phikhanh
Egbert, Melissa
Shapira, Marlene
Kobara, Katie
Parmar, Sheetal
Goel, Shruti
Prins, Sarah A.
Aruh, Israel
Persico, Nicola
Robins, Jared C.
Kirshon, Brian
Demko, Zachary P.
Ryan, Allison
Billings, Paul R.
Rabinowitz, Matthew
Benn, Peter
Martin, Kimberly A.
Hedriana, Herman L.
author_sort Norwitz, Errol R.
collection PubMed
description We analyzed maternal plasma cell-free DNA samples from twin pregnancies in a prospective blinded study to validate a single-nucleotide polymorphism (SNP)-based non-invasive prenatal test (NIPT) for zygosity, fetal sex, and aneuploidy. Zygosity was evaluated by looking for either one or two fetal genome complements, fetal sex was evaluated by evaluating Y-chromosome loci, and aneuploidy was assessed through SNP ratios. Zygosity was correctly predicted in 100% of cases (93/93; 95% confidence interval (CI) 96.1%–100%). Individual fetal sex for both twins was also called with 100% accuracy (102/102; 95% weighted CI 95.2%–100%). All cases with copy number truth were also correctly identified. The dizygotic aneuploidy sensitivity was 100% (10/10; 95% CI 69.2%–100%), and overall specificity was 100% (96/96; 95% weighted CI, 94.8%–100%). The mean fetal fraction (FF) of monozygotic twins (n = 43) was 13.0% (standard deviation (SD), 4.5%); for dizygotic twins (n = 79), the mean lower FF was 6.5% (SD, 3.1%) and the mean higher FF was 8.1% (SD, 3.5%). We conclude SNP-based NIPT for zygosity is of value when chorionicity is uncertain or anomalies are identified. Zygosity, fetal sex, and aneuploidy are complementary evaluations that can be carried out on the same specimen as early as 9 weeks’ gestation.
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spelling pubmed-66790812019-08-19 Validation of a Single-Nucleotide Polymorphism-Based Non-Invasive Prenatal Test in Twin Gestations: Determination of Zygosity, Individual Fetal Sex, and Fetal Aneuploidy Norwitz, Errol R. McNeill, Gabriel Kalyan, Akshita Rivers, Elizabeth Ahmed, Ebad Meng, Ling Vu, Phikhanh Egbert, Melissa Shapira, Marlene Kobara, Katie Parmar, Sheetal Goel, Shruti Prins, Sarah A. Aruh, Israel Persico, Nicola Robins, Jared C. Kirshon, Brian Demko, Zachary P. Ryan, Allison Billings, Paul R. Rabinowitz, Matthew Benn, Peter Martin, Kimberly A. Hedriana, Herman L. J Clin Med Article We analyzed maternal plasma cell-free DNA samples from twin pregnancies in a prospective blinded study to validate a single-nucleotide polymorphism (SNP)-based non-invasive prenatal test (NIPT) for zygosity, fetal sex, and aneuploidy. Zygosity was evaluated by looking for either one or two fetal genome complements, fetal sex was evaluated by evaluating Y-chromosome loci, and aneuploidy was assessed through SNP ratios. Zygosity was correctly predicted in 100% of cases (93/93; 95% confidence interval (CI) 96.1%–100%). Individual fetal sex for both twins was also called with 100% accuracy (102/102; 95% weighted CI 95.2%–100%). All cases with copy number truth were also correctly identified. The dizygotic aneuploidy sensitivity was 100% (10/10; 95% CI 69.2%–100%), and overall specificity was 100% (96/96; 95% weighted CI, 94.8%–100%). The mean fetal fraction (FF) of monozygotic twins (n = 43) was 13.0% (standard deviation (SD), 4.5%); for dizygotic twins (n = 79), the mean lower FF was 6.5% (SD, 3.1%) and the mean higher FF was 8.1% (SD, 3.5%). We conclude SNP-based NIPT for zygosity is of value when chorionicity is uncertain or anomalies are identified. Zygosity, fetal sex, and aneuploidy are complementary evaluations that can be carried out on the same specimen as early as 9 weeks’ gestation. MDPI 2019-06-28 /pmc/articles/PMC6679081/ /pubmed/31261782 http://dx.doi.org/10.3390/jcm8070937 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Norwitz, Errol R.
McNeill, Gabriel
Kalyan, Akshita
Rivers, Elizabeth
Ahmed, Ebad
Meng, Ling
Vu, Phikhanh
Egbert, Melissa
Shapira, Marlene
Kobara, Katie
Parmar, Sheetal
Goel, Shruti
Prins, Sarah A.
Aruh, Israel
Persico, Nicola
Robins, Jared C.
Kirshon, Brian
Demko, Zachary P.
Ryan, Allison
Billings, Paul R.
Rabinowitz, Matthew
Benn, Peter
Martin, Kimberly A.
Hedriana, Herman L.
Validation of a Single-Nucleotide Polymorphism-Based Non-Invasive Prenatal Test in Twin Gestations: Determination of Zygosity, Individual Fetal Sex, and Fetal Aneuploidy
title Validation of a Single-Nucleotide Polymorphism-Based Non-Invasive Prenatal Test in Twin Gestations: Determination of Zygosity, Individual Fetal Sex, and Fetal Aneuploidy
title_full Validation of a Single-Nucleotide Polymorphism-Based Non-Invasive Prenatal Test in Twin Gestations: Determination of Zygosity, Individual Fetal Sex, and Fetal Aneuploidy
title_fullStr Validation of a Single-Nucleotide Polymorphism-Based Non-Invasive Prenatal Test in Twin Gestations: Determination of Zygosity, Individual Fetal Sex, and Fetal Aneuploidy
title_full_unstemmed Validation of a Single-Nucleotide Polymorphism-Based Non-Invasive Prenatal Test in Twin Gestations: Determination of Zygosity, Individual Fetal Sex, and Fetal Aneuploidy
title_short Validation of a Single-Nucleotide Polymorphism-Based Non-Invasive Prenatal Test in Twin Gestations: Determination of Zygosity, Individual Fetal Sex, and Fetal Aneuploidy
title_sort validation of a single-nucleotide polymorphism-based non-invasive prenatal test in twin gestations: determination of zygosity, individual fetal sex, and fetal aneuploidy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679081/
https://www.ncbi.nlm.nih.gov/pubmed/31261782
http://dx.doi.org/10.3390/jcm8070937
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