Performance and Diagnostic Value of Genome-Wide Noninvasive Prenatal Testing in Multiple Gestations

Margot van Riel; Nathalie Brison; Machteld Baetens; Bettina Blaumeiser; François Boemer; Laura Bourlard; Saskia Bulk; Anne De Leener; Julie Désir; Koenraad Devriendt; Annelies Dheedene; Armelle Duquenne; Nathalie Fieremans; Annelies Fieuw; Jean-Stéphane Gatot; Bernard Grisart; Sandra Janssens; Naïri Khudashvili; Lore Lannoo; Axel Marichal; Colombine Meunier; Leonor Palmeira; Ilse Parijs; Bruno Pichon; Ellen Roets; Eva Sammels; Guillaume Smits; Marion Suenaert; Yves Sznajer; Kris Van den Bogaert; Leen Vancoillie; Lotte Vandeputte; Elise Vantroys; Joris Robert Vermeesch; Katrien Janssens

doi:10.1097/AOG.0000000000004385

Performance and Diagnostic Value of Genome-Wide Noninvasive Prenatal Testing in Multiple Gestations

Obstet Gynecol. 2021 Jun 1;137(6):1102-1108. doi: 10.1097/AOG.0000000000004385.

Affiliation

¹ Department of Human Genetics, Katholieke Universiteit Leuven, Leuven, the Center for Human Genetics and the Department of Obstetrics and Gynecology, Universitair Ziekenhuis Leuven, Leuven, the Center for Medical Genetics, Universitair Ziekenhuis Gent, Ghent, the Center for Medical Genetics, Universitair Ziekenhuis Antwerpen, Antwerp, the Center for Medical Genetics, Universiteit Antwerpen, Antwerp, the Center for Medical Genetics, Centre Hospitalier Universitaire de Liège, Liège, the Center for Human Genetics, Université Libre de Bruxelles, Brussels, the Center for Human Genetics, Université Catholique de Louvain, Brussels, the Center for Medical Genetics, Institut de Pathologie et de Génétique Gosselies, Charleroi, the Center for Medical Genetics, Vrije Universiteit Brussel, Brussels, and the Department of Obstetrics, Women's Clinic, Universitair Ziekenhuis Gent, Ghent, Belgium.

PMID: 33957658
DOI: 10.1097/AOG.0000000000004385

Abstract

Objective: To evaluate the accuracy and diagnostic value of genome-wide noninvasive prenatal testing (NIPT) for the detection of fetal aneuploidies in multiple gestations, with a focus on dichorionic-diamniotic twin pregnancies.

Methods: We performed a retrospective cohort study including data from pregnant women with a twin or higher-order gestation who underwent genome-wide NIPT at one of the eight Belgian genetic centers between November 1, 2013, and March 1, 2020. Chorionicity and amnionicity were determined by ultrasonography. Follow-up invasive testing was carried out in the event of positive NIPT results. Sensitivity and specificity were calculated for the detection of trisomy 21, 18, and 13 in the dichorionic-diamniotic twin cohort.

Results: Unique NIPT analyses were performed for 4,150 pregnant women with a multiple gestation and an additional 767 with vanishing gestations. The failure rate in multiple gestations excluding vanishing gestations ranged from 0% to 11.7% among the different genetic centers. Overall, the failure rate was 4.8%, which could be reduced to 1.2% after single resampling. There were no common fetal trisomies detected among the 86 monochorionic-monoamniotic and 25 triplet cases. Two monochorionic-diamniotic twins had an NIPT result indicative of a trisomy 21, which was confirmed in both fetuses. Among 2,716 dichorionic-diamniotic twin gestations, a sensitivity of 100% (95% CI 74.12-100%) and a specificity of 100% (95% CI 99.86-100%) was reached for trisomy 21 (n=12). For trisomy 18 (n=3), the respective values were 75% (95% CI 30.06-95.44%) sensitivity and 100% (95% CI 99.86-100%) specificity, and for trisomy 13 (n=2), 100% (95% CI 20.65-100%) sensitivity and 99.96% (95% CI 99.79-99.99%) specificity. In the vanishing gestation group, 28 NIPT results were positive for trisomy 21, 18, or 13, with only five confirmed trisomies.

Conclusion: Genome-wide NIPT performed accurately for detection of aneuploidy in dichorionic-diamniotic twin gestations.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Amniocentesis
Amnion / diagnostic imaging
Cell-Free Nucleic Acids / analysis
Chorion / diagnostic imaging
Diagnostic Errors
Down Syndrome / diagnosis*
False Negative Reactions
Female
Fetal Resorption* / diagnosis
Fetal Resorption* / genetics
Genome, Human
Humans
Noninvasive Prenatal Testing*
Pregnancy
Pregnancy, Multiple*
Pregnancy, Quadruplet
Pregnancy, Triplet
Pregnancy, Twin
Retrospective Studies
Sensitivity and Specificity
Trisomy
Trisomy 13 Syndrome / diagnosis*
Trisomy 18 Syndrome / diagnosis*

Substances

Cell-Free Nucleic Acids