Total and Fetal Circulating Cell-Free DNA, Angiogenic, and Antiangiogenic Factors in Preeclampsia and HELLP Syndrome.
BACKGROUND
Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by hypertension and proteinuria. The HELLP syndrome is the most severe form of PE. The aim of the present study was to determine different potential biomarkers that may help us perform an early diagnosis of the disease, assess on the severity of the disease, and/or predict maternal or fetal adverse outcomes.


METHODS
We measured serum levels of total and fetal circulating cell-free DNA (cfDNA), soluble endoglin, soluble form of vascular endothelial growth factor receptor, and placental growth factor in a healthy control group of pregnant women (n = 26), patients with mild (n = 37) and severe PE (n = 25), and patients with HELLP syndrome (n = 16).


RESULTS
We observed a gradual and strong relationship between all the biomarkers mentioned and the range of severity of PE, with the highest levels in patients with HELLP syndrome. Nevertheless, only the values of total cfDNA were able to significantly differentiate severe PE and HELLP syndrome (20957 ± 2784 vs. 43184 ± 8647 GE/ml, P = 0.01). Receiver operating characteristic (ROC) curves were constructed (i) for the healthy group with respect to the groups with PE and (ii) for patients with PE with respect to the group with HELLP syndrome; sensitivity and specificity values at different cutoff levels were calculated in each case. The maximum ROC area under the curve value for PE and HELLP syndrome (with respect to controls) was 0.91 (P < 0.001).


CONCLUSIONS
The measured biomarkers of cell damage, angiogenesis, and antiangiogenesis may reflect the severity of PE, with higher levels in patients who develop HELLP syndrome. In addition, these biomarkers may also help predict adverse fetal and maternal outcomes.
Laboratorio de Hipertensión Arterial e Hipercolesterolemia, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.|Laboratorio de Investigación clínica y traslacional en enfermedades hepáticas y digestivas. Instituto de Biomedicina de Sevilla (IBiS). Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Rocío
R
Muñoz-Hernández
Laboratorio de Hipertensión Arterial e Hipercolesterolemia, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.|Universidad Autónoma de Chile, Chile.
Pablo
P
Medrano-Campillo
Laboratorio de Hipertensión Arterial e Hipercolesterolemia, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.|Unidad Clínico-Experimental de Riesgo Vascular (UCERV-UCAMI), Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Maria L
ML
Miranda
Servicio de Bioquímica Clínica, Hospital Virgen del Rocío, Sevilla, Spain.
Hada C
HC
Macher
Unidad de Asesoría Estadística, Metodología y Evaluación de Investigación, Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI). Sevilla, Spain.
Jose Manuel
JM
Praena-Fernández
Laboratorio de Hipertensión Arterial e Hipercolesterolemia, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.|School of Public Health, Imperial College London. London, UK.
Antonio J
AJ
Vallejo-Vaz
Laboratorio de Hipertensión Arterial e Hipercolesterolemia, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
María J
MJ
Dominguez-Simeon
Laboratorio de Fisiopatología Vascular, Hospital de parapléjicos de Toledo. Toledo, Spain.
Rafael
R
Moreno-Luna
Laboratorio de Hipertensión Arterial e Hipercolesterolemia, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.|Unidad Clínico-Experimental de Riesgo Vascular (UCERV-UCAMI), Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Pablo
P
Stiefel
D000328:Adult; D042501:Angiogenic Proteins / Q000097:blood*; D019540:Area Under Curve; D016022:Case-Control Studies; D000073888:Cell-Free Nucleic Acids / Q000097:blood* / Q000235:genetics; D003937:Diagnosis, Differential; D000071063:Endoglin / Q000097:blood; D005260:Female; D017359:HELLP Syndrome / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D000072483:Placenta Growth Factor / Q000097:blood; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D011237:Predictive Value of Tests; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000097:blood; D012372:ROC Curve; D012720:Severity of Illness Index; D015854:Up-Regulation; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
D042501:Angiogenic Proteins; D000073888:Cell-Free Nucleic Acids; C064206:ENG protein, human; D000071063:Endoglin; C000608036:PGF protein, human; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
HELLP syndrome; angiogenic factors; antiangiogenic factors; blood pressure; cell-free DNA; hypertension; hypertension in pregnancy; maternal-fetal adverse outcomes; preeclampsia.