Role of Circulating Cell-free DNA Levels in Patients With Severe Preeclampsia and HELLP Syndrome

BACKGROUND Increased plasma levels of circulating cell-free DNA (c-f DNA) have been recently described in diseases related to ischemia and/or hypoxia. Preeclampsia (PCL) is a hypertensive disorder of pregnancy, of unknown origin, where a defective placentation resulting in placental ischemia plays an important role. HELLP syndrome (haemolysis, elevated liver enzymes, and low platelet count) is the most serious form of PCL. The origin of the disease is unknown, and there are no markers to help us to make an early diagnosis of disease or to predict patients who are at risk of suffering serious complications. METHODS We measured circulating c-f DNA levels in a group of control pregnant women (n = 20), patients with mild PCL (n = 9), patients with severe PCL (n = 24), and patients with HELLP syndrome (n = 8). RESULTS Values of circulating c-f DNA were 333.59 +/- 64.3 ng/ml in control subjects; 635.11 +/- 111.7 ng/ml in patients with mild PCL; 1,264.63 +/- 127.1 ng/ml in patients with severe PCL, and 1,595.95 +/- 269.8 ng/ml in patients with HELPP syndrome. (P < 0.0001). Values of c-f DNA >950 ng/ml had a sensitivity and specificity for detecting severe PCL and/or HELLLP syndrome of 0.71 and 0.93, respectively. CONCLUSIONS As far as we know, this is the first report of increased c-f DNA levels in HELLP syndrome. In this preliminary report, we have observed a gradual and strong relation between c-f DNA levels and range of severity of PCL, with it the highest in patients with HELLP syndrome. Further studies are needed for evaluating the utility of this technique in hypertensive disorders of pregnancy and, particularly, in HELLP syndrome.