Low fetal fraction of cell-free DNA predicts placental dysfunction and hypertensive disease in pregnancy

•Low fetal fraction of cfDNA may serve as a biomarker of placental compromise.•Low fetal fraction of cfDNA is associated with hypertensive disease in pregnancy.•Larger studies are required to determine association with neonatal outcomes. To examine the association of low fetal fraction of cell-free DNA (cfDNA) with placental compromise and adverse perinatal outcomes. This was a retrospective cohort utilizing a sample of convenience including 639 women undergoing cfDNA screening at our institution from January 2013 to January 2017. Low fetal fraction was defined as less than the 25th percentile. Indicators of placental compromise were examined individually and as a composite outcome, including hypertensive disease of pregnancy, intrauterine growth restriction, abruption, and oligohydramnios. Neonatal outcomes, including preterm delivery, low Apgar scores, and small for gestational age, also were examined. We calculated risk ratios (RR) and 95% confidence intervals (CI). Low fetal fraction was associated with placental compromise (RR 1.6 [CI 1.1–2.2]), hypertensive disease of pregnancy (RR 1.6 [CI 1.003–2.6]), and preeclampsia with severe features (RR 3.3 [CI 1.2–8.9]). Low fetal faction was not associated with preterm delivery, low Apgar scores, or small for gestational age. Low fetal fraction of cfDNA among asymptomatic women may serve as a predictor of subsequent placental dysfunction and hypertensive disease.