Factors affecting levels of circulating cell-free fetal DNA in maternal plasma and their implications for noninvasive prenatal testing

Prenat Diagn. 2015 Aug;35(8):816-22. doi: 10.1002/pd.4625. Epub 2015 Jul 14.

Abstract

Objective: Sufficient fetal DNA in a maternal plasma sample is required for accurate aneuploidy detection via noninvasive prenatal testing, thus highlighting a need to understand the factors affecting fetal fraction.

Method: The MaterniT21™ PLUS test uses massively parallel sequencing to analyze cell-free fetal DNA in maternal plasma and detect chromosomal abnormalities. We assess the impact of a variety of factors, both maternal and fetal, on the fetal fraction across a large number of samples processed by Sequenom Laboratories.

Results: The rate of increase in fetal fraction with increasing gestational age varies across the duration of the testing period and is also influenced by fetal aneuploidy status. Maternal weight trends inversely with fetal fraction, and we find no added benefit from analyzing body mass index or blood volume instead of weight. Strong correlations exist between fetal fractions from aliquots taken from the same patient at the same blood draw and also at different blood draws.

Conclusion: While a number of factors trend with fetal fraction across the cohort as a whole, they are not the sole determinants of fetal fraction. In this study, the variability for any one patient does not appear large enough to justify postponing testing to a later gestational age.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy*
  • Body Mass Index
  • Cell-Free System
  • DNA / blood*
  • Female
  • Fetus*
  • Gestational Age
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Maternal Serum Screening Tests / methods*
  • Pregnancy
  • Retrospective Studies
  • Sequence Analysis, DNA / methods*

Substances

  • DNA