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

Abstract

The villous trophoblast of the placenta undergoes continuous turnover during gestation, releasing cell free DNA (cfDNA) into maternal circulation. Quantitative analyses of fetal fraction of cfDNA suggest that abnormal concentrations may correlate with adverse outcomes; the directionality of this relationship remains unclear. This study examined the role of low fetal fraction of cfDNA among asymptomatic women in early pregnancy as a marker of subsequent placental compromise and adverse perinatal outcomes. This was a retrospective cohort using a convenience sample of 639 women with singleton pregnancies undergoing aneuploidy screening with non-invasive prenatal testing for advanced maternal age; abnormal serum screen or ultrasound findings; or patient request. We excluded women with chronic hypertension, an anomalous fetus, or abnormal cfDNA screening results. Indicators of placental compromise, including hypertensive disease of pregnancy, oligohydramnios, intrauterine growth restriction (IUGR), and abruption were assessed as individual outcomes and as a composite outcome. Low fetal fraction was defined as <25th percentile. We calculated BMI-adjusted risk ratios (aRR) and 95% confidence intervals (CI). Low fetal fraction was associated with the composite outcome of placental compromise (aRR 1.5; CI 1.1- 2.2). Low fetal fraction was also associated with individual outcomes of hypertensive disease of pregnancy (aRR 1.6; CI 1.003-2.6) and preeclampsia with severe features (aRR 3.3; CI 1.2-8.9). Though not significant, the incidence of oligohydramnios, IUGR, and low Apgars (<5 at 1 minute or <7 at 5 minutes) was greater in the low fetal fraction cohort. Low fetal fraction of cfDNA among asymptomatic women may serve as a biomarker for subsequent placental dysfunction and hypertensive disease. cfDNA testing may enhance the diagnostic value of traditional serum analogues, such as PAPP-A, in quantifying individual risk.View Large Image Figure ViewerDownload Hi-res image Download (PPT)