Fetal fraction of free-DNA: clinical-diagnostic parallels

Abstract

Introduction. Since 2011, a technology such as a non-invasive prenatal test (NIPT) has been used in the world i order o identify pregnant women at a high risk of giving birth to a child with chromosomal aneuploidy (CA). An important indicator of the test's effectiveness is the fetal fraction (FF), since its low level does not allow to give a reliable result to a patient.Aims: to determine the factors that can affect the level of FF during NIPT.Materials and methods. A retrospective comparative covenant study was carried out. The study included 288 patients who underwent NIPT in 2015-2018 after the standard complex of prenatal diagnosis (t 12-18 weeks of pregnancy). We assessed the correlation of the FF level with various clinical and anamnestic parameters and with indicators of biochemical screening for the first trimester (PAPP-A and β-ХГЧ). A comparison was made in terms of the FF level during pregnancy with a favorable and unfavorable outcome.Results. The average FF level in patient where CA was detected in the fetus was 9.01 (5.4-11)%, in the absence of CA — 9.7 (6.5-11.95)%, the difference are not statistically significant (p = 0.37). In patients with a physiological course of pregnancy, this indicator was 10.07 (6.6-12.57)%, and in patients with a complicated course of pregnancy, it was significantly lower — 8.11 (5.35-11.29)% (p = 0.02). We also analyzed the presence of a correlation between the level of FF and fetal weight at term, but no statistically significant correlation was found (r=0.13). There is a statistically significant inverse relationship between the FF level d the age of the pregnant woman, the patient's weight and body mass index, the number of pregnancies in the anamnesis, as well as a direct relationship between the FF and the β-hCG level (in MoM).Conclusions. FF is an important parameter of NIPT. A sufficient level of FF not only indicates a high reliability of the result obtained during NIPT, but also increases the chances of a favorable pregnancy outcome. The level of FF can be influenced by a number of clinical and anamnestic characteristics of the patient (weight body mass index, age, obstetric history). Studies aimed at determining the level of FF in various physiological and pathological conditions during pregnancy seem promising and thanks to them, it is possible that new models for predicting pregnancy complications will subsequently be proposed.