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

Abstract

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.

Factors Affecting the Fetal Fraction in Noninvasive Prenatal Screening: A Review

“…This may reflect poor placental function or reduced placental volume. PAPP-A and free β-hCG are placenta-derived proteins that circulate in maternal blood (56). These placenta-derived proteins and cffDNA may be influenced by common factors, such as placental trophoblast cell mass (57) and the contact surface area between maternal blood and the placenta (56).…”

“…PAPP-A and free β-hCG are placenta-derived proteins that circulate in maternal blood (56). These placenta-derived proteins and cffDNA may be influenced by common factors, such as placental trophoblast cell mass (57) and the contact surface area between maternal blood and the placenta (56). This may be the reason why the PAPP-A and free β-hCG levels are associated with FF.…”

Sex Differences Are Here to Stay: Relevance to Prenatal Care

“…This cffDNA originates from trophoblast cells and represents 3-6% of the total cell-free circulating DNA in maternal circulation during gestation. Of note, cffDNA levels may correlate with the levels of serum proteins including hCG [182]. Maternal cervical fluid is also a source of trophoblast-derived nucleic acids; cervical fluid has valuable diagnostic potential and can be used to accurately assess fetal sex [183].…”

Can the Cell-free DNA Test Predict Placenta Accreta Spectrum or Placenta Previa Totalis?

“…We now have enough evidence establishing that the use of the cffDNA test is too broad to be limited to genetic disorders [3]. After cell-free DNA was revealed to derive predominantly from the placenta, placenta-related pathologies present new topics of interest for researchers in maternal-fetal medicine [4,5,7,18].…”

“…Albery et al [2,3] presented two studies demonstrating that cell-free fetal DNA (cffDNA) originates from placental trophoblastic cells. With the contribution of additional studies, it was determined that the release of cffDNA is directly related to the extraction of the continual turnover of villous trophoblasts [4,5]. Once cffDNA was identified as a placental product, cell-free DNA testing attracted even more interest, and its potential increased as a non-invasive method of prenatal diagnosis for not only aneuploidies but also other obstetric complications [1].…”