Cell-Free Placental DNA in Maternal Plasma in Relation to Placental Health and Function

Fetal Diagn Ther. 2017;41(4):258-264. doi: 10.1159/000448707. Epub 2016 Aug 26.


Background: While cell-free placental DNA (cfp-DNA) increases in response to certain pathological conditions, confounding variables, such as placental size, may also contribute to its release. Furthermore, the relationship between cfp-DNA and maternal serum proteins has not been well investigated.

Objective: To analyze plasma cfp-DNA levels and correlate with measurable placental parameters, maternal serum proteins, or pathologic conditions reflecting placental dysfunction.

Method: Methylated fraction of RASSF1A was quantified in maternal plasma as a measure of cfp-DNA in a cohort of 86 pregnant women.

Results: Placental dimensions or weight had no impact on cfp-DNA levels in noncomplicated pregnancies (n = 63). However, an association between β-hCG and cfp-DNA levels (p = 0.0012) was detected. Complications occurred in 23 pregnancies including chromosomal abnormalities, gestational hypertension, intrauterine growth restriction, and preterm birth. There was overall a skewed distribution (<-1 SD or >1 SD from mean) for cfp-DNA in the abnormal group, although due to the small number of samples for each pathology, we provide only descriptive data to assess possible trends in cfp-DNA variation.

Conclusion: While cfp-DNA levels outside of the normal range may reflect placental distress, this relationship may be masked by a number of physiological confounders. The independence of cfp-DNA from β-hCG levels commonly assessed in pregnancy need to be further addressed.

Keywords: Cell-free DNA; Intrauterine growth restriction; Preeclampsia; Pregnancy; Prenatal screening; Preterm birth.

MeSH terms

  • Biomarkers / blood*
  • Cell-Free Nucleic Acids / blood*
  • Cohort Studies
  • Female
  • Humans
  • Maternal Serum Screening Tests / methods*
  • Placenta / physiology*
  • Plasma / metabolism*
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / diagnosis*


  • Biomarkers
  • Cell-Free Nucleic Acids