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

Prenat Diagn. 2022 Sep;42(10):1253-1261. doi: 10.1002/pd.6221. Epub 2022 Aug 22.


Objective: To evaluate if fetal fraction (FF) reported on cell-free DNA (cfDNA) screening is a marker for adverse obstetric outcomes.

Methods: 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.

Results: 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).

Conclusion: 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.

MeSH terms

  • Cell-Free Nucleic Acids*
  • Female
  • Fetus
  • Humans
  • Hypertension, Pregnancy-Induced* / diagnosis
  • Hypertension, Pregnancy-Induced* / epidemiology
  • Infant, Newborn
  • Pre-Eclampsia*
  • Pregnancy
  • Retrospective Studies


  • Cell-Free Nucleic Acids