Can fetal fractions in the cell-free DNA test predict the onset of fetal growth restriction?

Objective: To investigate the possible predictive value of fetal fraction in the cell-free DNA (cfDNA) test in pregnancies with early- and late-onset fetal growth restriction (FGR). Methods: This retrospective study comprised 247 women who were screened using the cfDNA test for aneuploidies during the first or second trimester and had deliveries at our institution from January 2016 to December 2019. The fetal fractions of women with early- (n =14) and late-onset (n=83) FGR and those with uncomplicated pregnancies (n=150) were compared. Results: The median fetal fractions for the early-onset FGR, late-onset FGR, and control groups were 5.7 [interquartile range (IQR) 2.65], 7 (IQR 5), and 735 (IQR 165), respectively. The fetal fractions were significantly lower in the early-onset FGR group than in the late-onset FGR and control groups (P= 0.047 and P=0.037, respectively). There was no difference in fetal fractions between the late-onset FGR and control groups (P=1.00). Conclusion: As a placenta-related disease, early-onset FGR had lower fetal fractions in the cfDNA test than uncomplicated pregnancies. For clinical use, lower fetal fractions can contribute as a biomarker for screening asymptomatic women for possible placenta-related diseases, such as early-onset 1:GR. However, more studies are needed to define the "lower" limit.