Maternal Plasma Fetal DNA Fractions in Pregnancies with Low and High Risks for Fetal Chromosomal Aneuploidies

Abstract

Recently published international guidelines recommend the clinical use of noninvasive prenatal test (NIPT) for aneuploidy screening only among pregnant women whose fetuses are deemed at high risk. The applicability of NIPT to aneuploidy screening among average risk pregnancies requires additional supportive evidence. A key determinant of the reliability of aneuploidy NIPT is the fetal DNA fraction in maternal plasma. In this report, we investigated if differences in fetal DNA fractions existed between different pregnancy risk groups. One hundred and ninety-five singleton pregnancies with male fetuses divided into 3 groups according to first trimester screening parameters were examined for fetal DNA percentage by counting Y chromosome DNA sequences using massively parallel sequencing. Fetal DNA fractions were compared between risk groups and assessed for correlations with first trimester screening parameters. There was no statistically significant difference in fetal DNA fractions across the high, intermediate and low risk groups. Fetal DNA fraction showed a strong negative correlation with maternal weight. Fetal DNA fraction also showed weak but significant correlations with gestational age, crown-rump length, multiple of medians of free β-subunit of human chorionic gonadotropin and pregnancy-associated plasma protein A. Similar fetal DNA fractions in maternal plasma between high, intermediate and low risk pregnant women is a precondition for uniform performance of the aneuploidy NIPTs for the general population. This study thus shows that the aneuploidy screening by NIPT is likely to offer similar analytical reliability without respect to the a priori fetal aneuploidy risk.

Use of Cell-Free DNA in the Investigation of Intrauterine Fetal Demise and Miscarriage

“…25 This could potentially provide clinical information regarding the presence of a genetic abnormality after 8 weeks of gestation among missed abortions compared with the 10-week threshold in viable pregnancies because a fetal fraction of at least 3.7% is likely to be obtained at that time. When genetic analysis is desired, cell-free DNA could possibly avoid a dilation and curettage and provide the opportunity for nonsurgical management.…”

Maternal X chromosome copy number variations are associated with discordant fetal sex chromosome aneuploidies detected by noninvasive prenatal testing

“…For female pregnancies, the normal range for ChrX and ChrY was − 3 b z b 3 whereas for male pregnancies, the normal range for ChrX and ChrY was z b −3 and z N 3, respectively. The percentage cell free fetal (cff) DNA in male pregnancies was calculated on the basis of the relative proportion of Y chromosome reads, as previously described [14].…”

Early fetal sexing in the rhinoceros by detection of male‐specific genes in maternal serum

“…Human fetal derived DNA in maternal plasma is of smaller size (Chan et al, ), accounts for 4% to 30% of the total DNA in maternal plasma, and is influenced by both maternal and fetal characteristics (Ashoor, Syngelaki, Poon, Rezende, & Nicolaides, ; Hudecova et al, ; Lo et al, ; Shi, Zhang, Cram, & Liu, ). Whether similar or lower concentrations of fetal DNA are present in the maternal plasma/serum of the non‐primate species for which this technique has also proven successful and where there is no direct contact between the placenta and maternal bloodstream is unknown.…”