Factors That Affect Cell-Free DNA Fetal Fraction in Twin Gestations

The most common reason for cell-free(cf) DNA test failure is low fetal fraction(FF). Data regarding factors that affect FF in twins are limited. We aimed to identify factors that affect FF and test failure in a large, diverse population of twin pregnancies. This is a planned secondary analysis of data from a large retrospective cohort study aimed to evaluate cfDNA screening performance for the common trisomies. The study population consisted of women with twin pregnancies who had cfDNA screening at 17 centers between 12/2011 – 2/2020. CfDNA testing was performed by a single lab using a MPSS approach. Vanishing twins and cases diagnosed with trisomy 21,18 and 13 were excluded. Student’s t-test was used as appropriate. Linear regression was used to adjust for the time of blood draw and a geometric mean was calculated with 95% CI. Logistic regression models were used for association between no result and patient characteristics. Of the 1642 cases included, 60(3.4%) had a non-reportable(NR) result on the first screen. 27 of 42(64%) cases with a second draw received a result. The mean FF for the entire cohort was 13.0 +/- 5.2. Obesity, lower gestational age(GA), Black race, treatment with aspirin(ASA) and low molecular heparin(LMWH) and chronic hypertension(CHTN) were associated with a lower mean FF(Table 1). Obese women(BMI ≥ 30) had a mean FF 3.8 percent lower than non-obese women after adjusting for GA at blood draw. Black race, obesity, CHTN and IVF were associated with NR results(Table 2). Black race and CHTN were not associated with increased risk for a NR result after adjustment for obesity and IVF. Obese women had a 5X greater risk of having a NR result compared to non-obese women. IVF was associated with a 2X increased risk of having a NR result. In twin pregnancies cfDNA FF increases with GA and decreases with obesity, Black race, treatment with ASA and LMWH and CHTN. Obesity and IVF are associated with an increased chance of cfDNA test failure. These factors are important to take into consideration in patients undergoing cfDNA screening.View Large Image Figure ViewerDownload Hi-res image Download (PPT)