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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6679081 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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