An analysis of factors affecting fetal fraction in cell-free fetal DNA test for aneuploidy screening

INTRODUCTION: To analyze factors affecting fetal fraction in cell-free DNA (cfDNA) test for aneuploidy screening.
METHODS: This is a retrospective cohort study conducted between 2018 and 2023. All pregnant women who had a cfDNA test for aneuploidy screening were included in the study. Maternal data, gestational age (GA) at the time of blood draw for the test, methodology of the chosen test, and results of cfDNA test (fetal fraction and risk status) were collected. Pregnancy outcome, GA at the time of delivery, pres-ence of hypertensive disorders of pregnancy (HDP), and neonatal outcomes were obtained and analyzed.
RESULTS: Data from a total of 447 women were analyzed. The median GA at the time of the cfDNA test was 12 (11–13) weeks. The median fetal fraction among women who have a healthy weight, who are overweight, and who are obese was 10.4% (7.7–13.1), 9% (7.1–12), and 7% (3.4–7.9), respectively (p=0.002). There were 12 (2.7%) cfDNA test results with low fetal fraction. All low fetal fraction results belonged to women who were obese (p<0.001). For each one-unit increase in BMI, there was a 0.4% drop in fetal fraction (95% CI 0.27–0.53). The decrease in fetal fraction remained significant when adjusted for maternal age and GA (-0.41, 95% CI 0.28–0.55). Maternal age, GA at the time of the test, and heparin and aspirin use were not associated with fetal fraction.
DISCUSSION AND CONCLUSION: Maternal BMI has a negative effect on fetal fraction in cfDNA testing. Pre-test counseling should include factors influencing the fetal fraction—and therefore the accuracy—of cfDNA testing.