Variability in Fetal Fraction Estimation: Comparing Fetal Fractions Reported by Noninvasive Prenatal Testing Providers Globally.

Autor:	Becking EC; Department of Obstetrics, Division of Women and Baby, Wilhelmina Childrens Hospital, University Medical Center Utrecht, Utrecht, The Netherlands., Linthorst J; Department of Human Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Amsterdam Reproduction and Development, Amsterdam, The Netherlands., Patton S; Manchester Science Park, EMQN CIC, Manchester, UK., Gutowska-Ding W; Manchester Science Park, EMQN CIC, Manchester, UK., Goodall R; Manchester Science Park, EMQN CIC, Manchester, UK., Khawaja F; Genomics Quality Assessment, NHS Lothian, Royal Infirmary of Edinburgh, Edinburgh, UK., Morgan F; Genomics Quality Assessment, NHS Lothian, Royal Infirmary of Edinburgh, Edinburgh, UK., Deans Z; Genomics Quality Assessment, NHS Lothian, Royal Infirmary of Edinburgh, Edinburgh, UK., Chitty LS; North Thames Genomic Laboratory Hub, Great Ormond Street NHS Foundation Trust and Genetics and Genomics, UCL Great Ormond Street Institute of Child Health, London, UK., Bekker MN; Department of Obstetrics, Division of Women and Baby, Wilhelmina Childrens Hospital, University Medical Center Utrecht, Utrecht, The Netherlands., Scheffer PG; Department of Obstetrics, Division of Women and Baby, Wilhelmina Childrens Hospital, University Medical Center Utrecht, Utrecht, The Netherlands., Sistermans EA; Department of Human Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Amsterdam Reproduction and Development, Amsterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Clinical chemistry [Clin Chem] 2023 Feb 01; Vol. 69 (2), pp. 160-167.
DOI:	10.1093/clinchem/hvac207
Abstrakt:	Background: Fetal fraction (FF) measurement is considered important for reliable noninvasive prenatal testing (NIPT). Using minimal FF threshold as a quality parameter is under debate. We evaluated the variability in reported FFs of individual samples between providers and laboratories and within a single laboratory. Methods: Genomic quality assessment and European Molecular Genetics Quality Network provide joint proficiency testing for NIPT. We compared reported FFs across all laboratories and stratified according to test methodologies. A single sample was sequenced repeatedly and FF estimated by 2 bioinformatics methods: Veriseq2 and SeqFF. Finally, we compared FFs by Veriseq and SeqFF in 87 351 NIPT samples. Results: For each proficiency test sample we observed a large variability in reported FF, SDs and CVs ranging from 1.7 to 3.6 and 17.0 to 35.8, respectively. FF measurements reported by single nucleotide polymorphism-based methods had smaller SDs (0.5 to 2.4) compared to whole genome sequencing-based methods (1.8 to 2.9). In the internal quality assessment, SDs were similar between SeqFF (SD 1.0) and Veriseq v2 (SD 0.9), but mean FF by Veriseq v2 was higher compared to SeqFF (9.0 vs 6.4, P 0.001). In patient samples, reported FFs were on average 1.12-points higher in Veriseq than in SeqFF (P 0.001). Conclusions: Current methods do not allow for a reliable and consistent FF estimation. Our data show estimated FF should be regarded as a laboratory-specific range, rather than a precise number. Applying strict universal minimum thresholds might result in unnecessary test failures and should be used with caution. (© American Association for Clinical Chemistry 2022.)
Databáze:	MEDLINE
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