1. The importance of determining the limit of detection of non-invasive prenatal testing methods
- Author
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Martina Mariano, Francesco Fiorentino, Laura Diano, Mariateresa Sessa, Arianna Polverari, Francesca Spinella, Sara Bono, Francesca Pizzuti, Sara Duca, and M. Baldi
- Subjects
0301 basic medicine ,Detection limit ,Fetus ,Pregnancy ,medicine.medical_specialty ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics ,Experimental model ,Non invasive ,Obstetrics and Gynecology ,Aneuploidy ,030105 genetics & heredity ,medicine.disease ,Bioinformatics ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,business ,Genetics (clinical) - Abstract
Objective Several non-invasive prenatal testing (NIPT) methods, which analyze circulating fetal cell-free DNA (cfDNA) in maternal plasma, suggest a fetal fraction (FF) ≥4% for a reportable result, with the assumption that fetal aneuploidies may not be detectable at lower FF. This study determined the actual limit of detection (LOD) of a massively parallel sequencing-based NIPT method and evaluated its performance in testing samples with low FF. Method An experimental model, involving the creation of artificial plasma mixtures with a final aneuploid FF ranging from 1% to 4%, simulated samples at different proportions of fetal cfDNA. We then analyzed 7103 blood samples, from pregnant women undergoing NIPT, to assess the impact of low FF on the performance of cfDNA testing. Results Detection of common aneuploidies in samples with an FF as low as 2% is well within the ability of this technology. Of 105 pregnancies confirmed chromosomally abnormal, 25 (23.8%) involving a 2%
- Published
- 2016
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