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Fibke C, Giroux S, Caron A, et al. Effect of preexamination conditions in a centralized-testing model of non-invasive prenatal screening. Clin Chem Lab Med. 2021;doi: 10.1515/cclm-2021-0652.
Fibke, C., Giroux, S., Caron, A., Starks, E., Parker, J. D. K., Swanson, L., Jouan, L., Langlois, S., Rouleau, G., Rousseau, F., & Karsan, A. (2021). Effect of preexamination conditions in a centralized-testing model of non-invasive prenatal screening. Clinical chemistry and laboratory medicine, . https://doi.org/10.1515/cclm-2021-0652
Fibke, Chad, et al. "Effect of preexamination conditions in a centralized-testing model of non-invasive prenatal screening." Clinical chemistry and laboratory medicine vol. (2021). doi: https://doi.org/10.1515/cclm-2021-0652
Fibke C, Giroux S, Caron A, Starks E, Parker JDK, Swanson L, Jouan L, Langlois S, Rouleau G, Rousseau F, Karsan A. Effect of preexamination conditions in a centralized-testing model of non-invasive prenatal screening. Clin Chem Lab Med. 2021 Nov 11; doi: 10.1515/cclm-2021-0652. Epub 2021 Nov 11. PMID: 34761647.
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Clin Chem Lab Med. 2021 Nov 11; doi: 10.1515/cclm-2021-0652. Epub 2021 Nov 11.

Effect of preexamination conditions in a centralized-testing model of non-invasive prenatal screening.

Clinical chemistry and laboratory medicine

Chad Fibke, Sylvie Giroux, André Caron, Elizabeth Starks, Jeremy D K Parker, Lucas Swanson, Loubna Jouan, Sylvie Langlois, Guy Rouleau, François Rousseau, Aly Karsan

Affiliations

  1. Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada.
  2. CRCHU de Québec - Université Laval, Québec, QC, Canada.
  3. Molecular Diagnostic Laboratory and Division of Medical Genetics, CHU Sainte-Justine, Montreal, QC, Canada.
  4. Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
  5. Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.
  6. Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.

PMID: 34761647 DOI: 10.1515/cclm-2021-0652

Abstract

OBJECTIVES: Non-invasive prenatal testing requires the presence of fetal DNA in maternal plasma. Understanding how preexamination conditions affect the integrity of cell-free DNA (cfDNA) and fetal fraction (FF) are a prerequisite for test implementation. Therefore, we examined the adjusted effect that EDTA and Streck tubes have on the cfDNA quantity and FF.

METHODS: A total of 3,568 maternal blood samples across Canada were collected in either EDTA, or Streck tubes, and processing metrics, maternal body mass index (BMI), gestational age and fetal karyotype and sex were recorded. Plasma samples were sequenced using two different sequencing platforms in separate laboratories. Sequencing data were processed with SeqFF to estimate FF. Linear regression and multivariate imputation by chained equations were used to estimate the adjusted effect of tube type on cfDNA and FF.

RESULTS: We found a positive association between cfDNA quantity and blood shipment time in EDTA tubes, which is significantly reduced with the use of Streck tubes. Furthermore, we show the storage of plasma at -80 °C is associated with a 4.4% annual relative decrease in cfDNA levels. FF was not associated with collection tube type when controlling for confounding variables. However, FF was positively associated with gestational age and trisomy 21, while negatively associated with BMI, male fetus, trisomy 18, Turners syndrome and triploidy.

CONCLUSIONS: Preexamination, maternal and fetal variables are associated with cfDNA quantity and FF. The consideration of these variables in future studies may help to reduce the number of pregnant women with inconclusive tests as a result of low FF.

© 2021 Walter de Gruyter GmbH, Berlin/Boston.

Keywords: aneuploidy; cfDNA; fetal fraction; non-invasive prenatal testing (NIPT); preanalytical; stabilized blood collection tube

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