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

• Published in: Prenatal diagnosis Vol. 42; no. 10; pp. 1253 - 1261
• Main Authors: Madala, Deeksha, Maktabi, Mohamad Ali, Sabbagh, Riwa, Erfani, Hadi, Moon, Andrea, Veyver, Ignatia B.
• Format: Journal Article
• Language: English
• Published: Charlottesville Wiley Subscription Services, Inc 01-09-2022
• Subjects: Complications; Deoxyribonucleic acid; Diabetes mellitus; Disorders; DNA; Fetuses; Genetic screening; Hypertension; Markers; Medical records; Morbidity; Pregnancy; Pregnancy complications
• ISSN: 0197-3851; 1097-0223
• DOI: 10.1002/pd.6221

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.
Key points
What is already known about this topic?
Analysis of cell‐free DNA circulating in maternal blood is used for noninvasive prenatal screening for fetal aneuploidies.
The fetal fraction (FF) is the proportion of circulating cell‐free DNA (cfDNA) that is of fetal (placental) origin.
Several maternal and fetal factors such as maternal weight and fetal gestational age can affect FF.
What does this study add?
This study shows that lower fetal fractions reported on clinical cfDNA screening results correlate with the presence of hypertensive disorders of pregnancy.