Comparing methods for fetal fraction determination and quality control of NIPT samples

Daphne M. van Beek, Roy Straver, Marian M. Weiss, Elles M.J. Boon, Karin Huijsdens-van Amsterdam, Cees B.M. Oudejans, Marcel J.T. Reinders, Erik A. Sistermans

Research output: Contribution to journalArticleAcademicpeer-review

40 Citations (Scopus)


Objective: To compare available analysis methods for determining fetal fraction on single read next generation sequencing data. This is important as the performance of non-invasive prenatal testing (NIPT) procedures depends on the fraction of fetal DNA. Methods: We tested six different methods for the detection of fetal fraction in NIPT samples. The same clinically obtained data were used for all methods, allowing us to assess the effect of fetal fraction on the test result, and to investigate the use of fetal fraction for quality control. Results: We show that non-NIPT methods based on body mass index (BMI) and gestational age are unreliable predictors of fetal fraction, male pregnancy specific methods based on read counts on the Y chromosome perform consistently and the fetal sex-independent new methods SeqFF and SANEFALCON are less reliable but can be used to obtain a basic indication of fetal fraction in case of a female fetus. Conclusion: We recommend the use of a combination of methods to prevent the issue of reports on samples with insufficient fetal DNA; SANEFALCON to check for presence of fetal DNA, SeqFF for estimating the fetal fraction for a female pregnancy and any Y-based method for estimating the fetal fraction for a male pregnancy.

Original languageEnglish
Pages (from-to)769-773
Number of pages5
JournalPrenatal diagnosis
Issue number8
Early online date2017
Publication statusPublished - 1 Aug 2017

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