Association Between Fetal Fraction on Cell-Free DNA Testing and First-Trimester Markers for Pre-eclampsia

Screening for chromosomal abnormalities based on cell-free fetal DNA (cfDNA) has been clinically available since 2011. While highly accurate for detection of trisomy 21, the accuracy of the test depends on the proportion of the total cfDNA that contains fetal genetic material (ie, the fetal fraction [FF]), with accuracy being higher when the FF is high and lower when the FF is low. Because cell-free "fetal" DNA originates from the developing placenta, studies have suggested that the release of cfDNA might be related to the size of the placenta and the rate of trophoblastic apoptosis. Although various studies show an increase in both fetal and total cfDNA in the maternal circulation in women diagnosed with preeclampsia (PE), little is known regarding FF in these cases and whether its measurement could be used as a marker of placental dysfunction in asymptomatic women. These researchers performed a retrospective cohort study including all women with a singleton pregnancy who had risk calculation for PE and fetal growth restriction (FGR) between 11 + 0 and 13 + 6 weeks' gestation and who also had cfDNA as a primary or secondary screening test for chromosomal abnormalities at any gestational age at 2 fetal medicine clinics in Sydney and Melbourne, Australia, between March 2013 and May 2017. Logarithmically transformed FF results were adjusted for gestational age and maternal characteristics. Associations with mean arterial pressure,mean uterine artery pulsatility index, pregnancy-associated plasma protein A (PAPP-A), placental growth factor, and risks of PE at less than 34 weeks, PE at less than 37 weeks, and FGR at less than 37 weeks were analyzed using correlation analysis and univariable and multivariable linear regressions. In total, 4317 singleton pregnancies that underwent cfDNA testing with FF reported were included. Significant prediction of FF was provided by gestational age, conception by in vitro fertilization, maternal age, body mass index, chronic hypertension, diabetes mellitus, South Asian ethnicity, and being parous without a history of PE or FGR. Fetal fraction was associated inversely with mean arterial pressure and mean uterine artery pulsatility index and associated positively with PAPP-A and placental growth factor. The lower the FF, the higher were the risks of PE at less than 34 weeks, PE at less than 37 weeks, and FGR at less than 37 weeks (P < 0.001 for all). The researchers concluded that there is a significant association between FF and first-trimester markers for adverse pregnancy outcome. Low FF is associated with an increased risk of pregnancy complications, but its capacity to act an as independent first-trimester marker in an algorithm for screening for PE and FGR requires further research.