EP18.23: Analysis of determinants of fetal fraction in cell‐free fetal DNA testing

Fetal fraction (FF) ensures that there is enough placental cell-free DNA (cfDNA) in maternal plasma to produce a reliable result. The detection rates decrease with reducing FF, leading to a “no call” result. Therefore, it is crucial to identify the factors contributing to low FF. Our study aims to investigate and analyse the factors that contribute to low FF in cffDNA testing and to provide a comprehensive understanding of the determinants of low FF to improve the performance of cffDNA testing as a prenatal screening tool. A retrospective cohort study encompassing all antenatal women who underwent cffDNA testing for fetal aneuploidies at the Maternal and Fetal Medicine Unit during the study period(2019-2023) Next Generation Sequencing was employed to analyse fetal and maternal alleles and thus ascertain the proportion of cell-free DNA (cfDNA) originating from the fetus. Multivariable regression analysis was utilised to identify the significant determinants of fetal cell fraction. Fetal fraction exhibited a significant positive linear correlation with gestational age (r= 0.169), and a significant negative correlation with maternal age (r= -0.103) and BMI (r=-0.281).Low fetal fraction was significantly associated with advanced maternal age (≥35 years), high BMI (≥35), IVF pregnancies, maternal overt diabetes/autoimmune diseases, IVF pregnancies and low serum biochemical markers (PAPPA and HCG). There were no significant differences found in twin pregnancies or between male and female fetuses. Low fetal fraction correlated significantly with higher rates of fetal aneuploidies, increased risk of pre-eclampsia, severe pre-eclampsia with impending symptoms, small for gestational age babies, fetal growth restriction and NICU stay. A comprehensive understanding of the factors influencing low fetal fraction enhances the interpretation of this parameter, aiding in the management of women with inconclusive cffDNA testing results. Additionally, these women can be counselled about potential adverse maternal and perinatal outcomes associated with low fetal fraction.