Fetal fraction in maternal plasma cell-free DNA at 11-13 weeks' gestation: effect of maternal and fetal factors

Fetal Diagn Ther. 2012;31(4):237-43. doi: 10.1159/000337373. Epub 2012 May 4.


Objective: It was the aim of this study to examine the possible effects of maternal and fetal characteristics on the fetal fraction in maternal plasma cell-free DNA (cfDNA) at 11-13 weeks' gestation.

Methods: In a nested case-control study, cfDNA was extracted from maternal plasma obtained before chorionic villous sampling from 300 euploid, 50 trisomy 21 and 50 trisomy 18 pregnancies at 11-13 weeks' gestation. Chromosome-selective sequencing of maternal cfDNA non-polymorphic and polymorphic loci, where fetal alleles differ from maternal alleles, was used to determine the proportion of DNA which is of fetal origin. Multivariate regression analysis was used to determine which of the factors amongst maternal weight, racial origin, smoking status, plasma storage time, serum pregnancy-associated plasma protein (PAPP)-A and free β-subunit of human chorionic gonadotropin (β-hCG), fetal crown-rump length, nuchal translucency thickness, gender and karyotype were significant predictors of the fetal fraction.

Results: Significant independent prediction of fetal fraction was provided by maternal weight, serum PAPP-A and serum free β-hCG multiples of the median, but not by other maternal characteristics, fetal karyotype, crown-rump length or nuchal translucency thickness. Fetal fraction increased with serum metabolite levels and decreased with maternal weight.

Conclusions: The fetal fraction in maternal plasma cfDNA increases with serum PAPP-A and free β-hCG and decreases with maternal weight.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Weight
  • Case-Control Studies
  • Chorionic Gonadotropin, beta Subunit, Human / blood*
  • Chorionic Villi Sampling
  • Chromosomes, Human, Pair 18
  • DNA / blood*
  • Down Syndrome / blood
  • Down Syndrome / genetics
  • Female
  • Fetus*
  • Gestational Age*
  • Humans
  • Karyotyping
  • Pregnancy
  • Pregnancy-Associated Plasma Protein-A / analysis*
  • Prenatal Diagnosis / methods*
  • Trisomy / diagnosis
  • Trisomy / genetics


  • Chorionic Gonadotropin, beta Subunit, Human
  • DNA
  • Pregnancy-Associated Plasma Protein-A