84: First trimester free fetal DNA in the maternal circulation as a predictor of preeclampsia

Abstract

circulation as a predictor of preeclampsia Bob Silver University of Utah Health Sciences Center and Intermountain Healthcare, Obstetrics and Gynecology, Salt Lake City, UT OBJECTIVE: To assess the relationship between cell-free fetal (CFF) DNA in maternal plasma in the first trimester and the subsequent development of preeclampsia. STUDY DESIGN: Nested case-control study of patients enrolled in the CAPPS prediction study (RCT of antioxidants for the prevention of preeclampsia) of 175 women who did and 175 women who did not develop preeclampsia. DNA was extracted from 600 L of maternal plasma obtained between 9 13 weeks gestation that had been frozen at 700C. Quantitative real time PCR using Taqman chemistry was used to amplify genes specific for the RASSF1A (methylated in the fetus) and B-actin (control) genes with and without digestion with the methylation sensitive enzymes Hinp1I and HhaI. Standard curves were generated using serial dilutions of a known DNA standard and samples were normalized. RESULTS: Women with and without preeclampsia were similar with regard to age, gestational age at blood-draw, education, smoking and race. As expected, cases had higher systolic and diastolic BP and BMI at the time of enrollment compared to controls. Total free DNA was higher in African American (median; 25 75%; 6.15; 0.14 28.7; p 0.024) and Hispanic (4.95; 0.20 26.82; p 0.037) compared to white women (2.33; 0.03 13.10). Levels of total free DNA also increased with increasing maternal BMI (p 0.016). After adjustment for BMI and race, total and fetal free DNA levels were similar between women with preeclampsia and controls. Levels of total free DNA were more predictive of preeclampsia in African Americans (ROC-AUC 0.69; 95% CI: 0.60 0.79; p 0.064). In African Americans, at levels 70, there was a 60.7% sensitivity and 80.4% specificity for the prediction of preeclampsia. CONCLUSION: Levels of total free DNA in the first trimester are increased in African American and Hispanic compared to white women, and levels increase with increasing BMI. There is no significant difference in levels of total or free fetal DNA in the first trimester in women who subsequently develop preeclampsia.