Lower fetal fraction in clinical cell-free DNA screening results is associated with increased risk of hypertensive disorders of pregnancy.

Abstract

To evaluate if fetal fraction (FF) reported on cell-free DNA (cfDNA) screening is a marker for adverse obstetric outcomes. We retrospectively reviewed medical records from a cohort of women with singleton pregnancies who had cfDNA screening. We evaluated if reported FF could predict the following pregnancy complications: hypertensive disorders of pregnancy (HDP), fetal growth restriction, preterm delivery, gestational diabetes mellitus, or a composite maternal morbidity, defined as the presence of at least one of these outcomes. Receiver operating curve analysis was performed on FF from 534 women to define the FF that differentiated a low FF group (<10%; N=259) and a high FF group (≥10%; N=275). Hypertensive disorders of pregnancy were more common for women in the low FF group (32.0% vs. 11.6% and p<0.001), who had a two-fold odds of developing HDP (p=0.006). Composite maternal morbidity was also more common for women in the low FF group (51.4% vs. 30.2% and p<0.001), who had a 1.7-fold odds of developing any of the adverse obstetrical outcomes (p=0.014). We found that low FF on cfDNA screening is associated with an increased risk of HDP. Fetal fraction reported that cfDNA screening reports have potential as a predictive marker for the development of HDP and adverse outcomes.