An important reminder that cell-free DNA is mostly maternal

Cell-free DNA screening is specially designed to tell you about fetal chromosome abnormalities. But did you know it will sometimes tell you something clinically significant about mom?

Cell-free DNA (cfDNA) screening can be used to detect sex chromosome aneuploidies during pregnancy.1,2 Because maternal blood contains a mixture of ~90% maternal and ~10% fetal DNA, abnormal sex chromosome results can sometimes be maternal in origin.3,4

We reviewed 975 total cases of suspected sex chromosome aneuploidy on cfDNA screening with outcome data available on 587 of those cases.

What did we find?

  • Of the 975 cases of sex chromosome aneuploidies, 67 (7%) were reported as suspected maternal origin.
  • Fetal diagnostic testing results available for those cases suspected to be maternal in origin were all normal.
Our findings suggest that there is value in reporting suspected maternal origin of sex chromosome aneuploidies, as this may affect decisions regarding follow-up testing.
This research was presented at the 2020 American College of Medical Genetics (ACMG) Annual Clinical Genetics Meeting, Digital Edition. Download the poster


  1. Gil MM, et al. Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol. 2017 Sep;50(3):303-314.
  2. Mazloom Ar, et al. Noninvasive prenatal detection of sex chromosomal aneuploidies by sequencing circulating cell-free DNA from maternal plasma. Prenat Diagn. 2013 Jun;33(6)591-597.
  3. Wang Y, et al. Maternal mosaicism is a significant contributor to discordant sex chromosomal aneuploidies associated with noninvasive prenatal testing. Clin Chem. 2014 Jan;60(1):251-259.
  4. Zhang B, et al. High false‐positive non‐invasive prenatal screening results for sex chromosome abnormalities: Are maternal factors the culprit? Prenat Diagn. 2019 Jul.
  5. Reeves et al. Suspected maternal vs. fetal sex chromosome cell-free DNA screening results impact diagnostic testing uptake and follow up. Poster presented at the 2020 ACMG Annual Clinical Genetics Meeting, Digital Edition.