OBJECTIVE: In this study, we expanded conventional cell-free fetal DNA (cfDNA)-based non-invasive prenatal testing (NIPT) to cover the entire genome. We aimed to compare the performance of the two tests in a large general population of pregnant women, in order to assess the clinical utility of the genome-wide screening. METHOD: Genome-wide cfDNA analysis was offered to 12 114 pregnant women undergoing NIPT for common fetal aneuploidy. Sequencing data were analyzed using an algorithm optimized to identify aneuploidies and subchromosomal aberrations. RESULTS: Genome-wide screening allowed detection of 12 (7.4%) potentially viable clinically relevant chromosomal abnormalities, which would have remained overlooked if only conventional NIPT had been performed. This resulted in a statistically significant higher sensitivity (100% vs 92.64%, p < 0.001) than did standard screening. This was achieved without sacrificing the specificity of the test, which resulted similar to that obtained with standard cfDNA testing (99.87% vs 99.77%, p = 0.064). CONCLUSION: Genome-wide cfDNA analysis represents an enhanced screening tool for prenatal detection of chromosomal abnormalities, allowing identification of clinically relevant imbalances that are not detectable by conventional cfDNA testing. The results of this study demonstrate the clinical utility of genome-wide cfDNA analysis. This level of screening provides a significant higher sensitivity compared to standard screening while maintaining a high specificity, with the potential to improve overall pregnancy management.
OBJECTIVE: In this study, we expanded conventional cell-free fetal DNA (cfDNA)-based non-invasive prenatal testing (NIPT) to cover the entire genome. We aimed to compare the performance of the two tests in a large general population of pregnant women, in order to assess the clinical utility of the genome-wide screening. METHOD: Genome-wide cfDNA analysis was offered to 12 114 pregnant women undergoing NIPT for common fetal aneuploidy. Sequencing data were analyzed using an algorithm optimized to identify aneuploidies and subchromosomal aberrations. RESULTS: Genome-wide screening allowed detection of 12 (7.4%) potentially viable clinically relevant chromosomal abnormalities, which would have remained overlooked if only conventional NIPT had been performed. This resulted in a statistically significant higher sensitivity (100% vs 92.64%, p < 0.001) than did standard screening. This was achieved without sacrificing the specificity of the test, which resulted similar to that obtained with standard cfDNA testing (99.87% vs 99.77%, p = 0.064). CONCLUSION: Genome-wide cfDNA analysis represents an enhanced screening tool for prenatal detection of chromosomal abnormalities, allowing identification of clinically relevant imbalances that are not detectable by conventional cfDNA testing. The results of this study demonstrate the clinical utility of genome-wide cfDNA analysis. This level of screening provides a significant higher sensitivity compared to standard screening while maintaining a high specificity, with the potential to improve overall pregnancy management.
Authors: Karuna R M van der Meij; Erik A Sistermans; Merryn V E Macville; Servi J C Stevens; Caroline J Bax; Mireille N Bekker; Caterina M Bilardo; Elles M J Boon; Marjan Boter; Karin E M Diderich; Christine E M de Die-Smulders; Leonie K Duin; Brigitte H W Faas; Ilse Feenstra; Monique C Haak; Mariëtte J V Hoffer; Nicolette S den Hollander; Iris H I M Hollink; Fernanda S Jehee; Maarten F C M Knapen; Angelique J A Kooper; Irene M van Langen; Klaske D Lichtenbelt; Ingeborg H Linskens; Merel C van Maarle; Dick Oepkes; Mijntje J Pieters; G Heleen Schuring-Blom; Esther Sikkel; Birgit Sikkema-Raddatz; Dominique F C M Smeets; Malgorzata I Srebniak; Ron F Suijkerbuijk; Gita M Tan-Sindhunata; A Jeanine E M van der Ven; Shama L van Zelderen-Bhola; Lidewij Henneman; Robert-Jan H Galjaard; Diane Van Opstal; Marjan M Weiss Journal: Am J Hum Genet Date: 2019-11-07 Impact factor: 11.025
Authors: Alice E Hughes; Michael Nodzenski; Robin N Beaumont; Octavious Talbot; Beverley M Shields; Denise M Scholtens; Bridget A Knight; William L Lowe; Andrew T Hattersley; Rachel M Freathy Journal: Diabetes Date: 2018-02-20 Impact factor: 9.461
Authors: Diane Van Opstal; Merel C van Maarle; Klaske Lichtenbelt; Marjan M Weiss; Heleen Schuring-Blom; Shama L Bhola; Mariette J V Hoffer; Karin Huijsdens-van Amsterdam; Merryn V Macville; Angelique J A Kooper; Brigitte H W Faas; Lutgarde Govaerts; Gita M Tan-Sindhunata; Nicolette den Hollander; Ilse Feenstra; Robert-Jan H Galjaard; Dick Oepkes; Stijn Ghesquiere; Rutger W W Brouwer; Lean Beulen; Sander Bollen; Martin G Elferink; Roy Straver; Lidewij Henneman; Godelieve C Page-Christiaens; Erik A Sistermans Journal: Genet Med Date: 2017-09-28 Impact factor: 8.822
Authors: Diane Van Opstal; Stefanie van Veen; Marieke Joosten; Karin E M Diderich; Lutgarde C P Govaerts; Joke Polak; Nicole van Koetsveld; Marjan Boter; Attie T J I Go; Dimitri N M Papatsonis; Krista Prinsen; Lies H Hoefsloot; Malgorzata I Srebniak Journal: Prenat Diagn Date: 2019-08-13 Impact factor: 3.050
Authors: Diane Van Opstal; Karin E M Diderich; Marieke Joosten; Lutgarde C P Govaerts; Joke Polak; Marjan Boter; Jasper J Saris; Wai Yee Cheung; Stefanie van Veen; Robert van de Helm; Attie T J I Go; Maarten F C M Knapen; Dimitri N M Papatsonis; Anneke Dijkman; Femke de Vries; Robert-Jan H Galjaard; Lies H Hoefsloot; Malgorzata I Srebniak Journal: Prenat Diagn Date: 2018-09-27 Impact factor: 3.050