At Preeclampsia Diagnosis, Total Cell‐Free DNA Concentration is Elevated and Correlates With Disease Severity
Open Access
- 3 August 2021
- journal article
- research article
- Published by Wolters Kluwer Health in Journal of the American Heart Association
- Vol. 10 (15) , e021477
Abstract
Background: Placental derived cell‐free DNA (cfDNA), widely utilized for prenatal screening, may serve as a biomarker for preeclampsia. To determine whether cfDNA parameters are altered in preeclampsia, we conducted a case‐control study using prospectively collected maternal plasma (n=20 preeclampsia, n=22 normal) using our in‐house validated prenatal screening assay. Methods and Results: Isolated cfDNA was quantified, sequenced using Illumina NextSeq 500, and the placental‐derived fraction was determined. Clinical and test characteristics were compared between preeclampsia and controls, followed by comparisons within the preeclampsia cohort dichotomized by cfDNA concentration. Lastly, cfDNA parameters in preeclampsia were correlated with markers of disease severity. Maternal age, body mass index, gestational age at delivery, cesarean rate, and neonatal birthweight were expectedly different between groups ( P ≤0.05). The placental‐derived cfDNA fraction did not differ between groups (21.4% versus 16.9%, P =0.06); however, total cfDNA was more than 10 times higher in preeclampsia (1235 versus 106.5 pg/µL, P P =0.01). The dichotomized preeclampsia group with the highest cfDNA concentration delivered earlier (33.2 versus 36.6 weeks, P =0.02) and had lower placental‐derived fractions (9.1% versus 21.4%, P =0.04). Among preeclampsia cases, higher total cfDNA correlated with earlier gestational age at delivery ( P =0.01) and higher maximum systolic blood pressure ( P =0.04). Conclusions: At diagnosis, total cfDNA is notably higher in preeclampsia, whereas the placental derived fraction remains similar to healthy pregnancies. In preeclampsia, higher total cfDNA correlates with earlier gestational age at delivery and higher systolic blood pressure. These findings may indicate increased release of cfDNA from maternal tissue injury.Keywords
This publication has 31 references indexed in Scilit:
- Can the quantity of cell‐free fetal DNA predict preeclampsia: a systematic reviewPrenatal Diagnosis, 2014
- Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testingProceedings of the National Academy of Sciences, 2014
- Cellular Fetal Microchimerism in PreeclampsiaHypertension, 2013
- Fetal fraction in maternal plasma cell‐free DNA at 11–13 weeks' gestation: relation to maternal and fetal characteristicsUltrasound in Obstetrics & Gynecology, 2012
- Hypertension in Pregnancy and Later Cardiovascular RiskCirculation, 2010
- Relationship of circulating cell-free DNA levels to cell-free fetal DNA levels, clinical characteristics and laboratory parameters in preeclampsiaBMC Medical Genetics, 2009
- First-trimester maternal plasma cell-free fetal DNA and preeclampsiaAmerican Journal of Obstetrics and Gynecology, 2009
- Two-stage elevation of cell-free fetal DNA in maternal sera before onset of preeclampsiaAmerican Journal of Obstetrics and Gynecology, 2004
- Is the Association Between Parity and Coronary Heart Disease Due to Biological Effects of Pregnancy or Adverse Lifestyle Risk Factors Associated With Child-Rearing?Circulation, 2003
- Elevation of both maternal and fetal extracellular circulating deoxyribonucleic acid concentrations in the plasma of pregnant women with preeclampsiaAmerican Journal of Obstetrics and Gynecology, 2001