Factors affecting cell-free DNA fetal fraction and the consequences for test accuracy

Abstract

The fetal fraction in maternal plasma cfDNA increased with gestational age, serum pregnancy-associated plasma protein A (PAPP-A), β-hCG, and PlGF and decreased with increasing maternal BMI. There was no significant correlation between low FF and test accuracy, when FF was above 4%.

Implications of failure to achieve a result from prenatal maternal serum cell‐free DNA testing: a historical cohort study

“…Our study provides further evidence that increased BMI is correlated with decreased fetal fraction, as has been established in previous studies . Furthermore, other studies including that by Ashoor et al found that fetal fraction also varied depending on ethnicity, although this was not explored in our study .…”

“…31 Our study provides further evidence that increased BMI is correlated with decreased fetal fraction, as has been established in previous studies. 13,23,26 Furthermore, other studies including that by Ashoor et al found that fetal fraction also varied depending on ethnicity, although this was not explored in our study. 13 The reported reasons for failure in our study are distributed in a similar fashion to those demonstrated previously with both Benn and Norton and their colleagues reporting that around half of the 'no results' in their studies were attributable to low fetal fraction.…”

“…Pre‐eclampsia is theorised to develop as a result of impaired invasion by the trophoblasts during early gestation leading to abnormal placentation . It is feasible that this same pathological process might then cause abnormal apoptosis of these trophoblasts, resulting in abnormal amounts of cffDNA being released into the maternal blood that is required for analysis in NIPT …”

“…25 It is feasible that this same pathological process might then cause abnormal apoptosis of these trophoblasts, resulting in abnormal amounts of cffDNA being released into the maternal blood that is required for analysis in NIPT. 26 The study cohort had a higher BMI than the general Australian obstetric population. The only significant difference demonstrated between those women who had insufficient fetal fraction and those who did not receive a result from NIPT for other reasons was an increased BMI, which suggests a dilutional effect and increased maternal adipocyte turnover as the principal causes.…”

Does Maternal Body Mass Index Affect the Quantity of Circulating Fetal Cells Available to Use for Cell-Based Noninvasive Prenatal Test in High-Risk Pregnancies?

“…However, cffNIPT performance highly depends on the fetal fraction (FF), defined as the proportion of fetal-derived cell-free DNA in the total cell-free DNA component found in maternal plasma. Thus, the FF must exceed 3–4% to provide a low false negative rate [2]. Several factors including body mass index (BMI) affect the FF.…”