Parallel Assessment of Circulatory Fetal DNA and Corticotropin-Releasing Hormone mRNA in Early- and Late-Onset Preeclampsia

Preeclampsia, a severe disorder of human pregnancy of unknown etiology, remains a major cause of fetal and maternal mortality (1)(2). Because of the heterogeneous nature of this disorder, it has been suggested that preeclampsia could be subclassified into two distinct forms to better understand the underlying causes (3). These two forms, termed early and late onset, are defined as the development of symptoms before or after 34 weeks of pregnancy, respectively (3). Results of several studies have indicated that the early-onset form is more severe, frequently leading to the delivery of growth-retarded premature babies, whereas the late-onset form is more evanescent and clinically of lesser importance (4). Previous studies have indicated that cell-free fetal DNA and mRNA concentrations are increased in preeclampsia (5)(6)(7)(8). Because these studies focused on either cell-free DNA or RNA alone, we examined the concentrations of these nucleic acids simultaneously in cases with early- and late-onset preeclampsia. Approval for this study was granted by the respective Institutional Review Boards (Basel and Stellenbosch), and export of biological material was approved by the South African Department of Health. Written informed consent was obtained in all instances. In our study, maternal blood samples were collected from 37 pregnant women with manifest preeclampsia. Preeclampsia was defined by new-onset blood pressure of at least 140/90 mmHg in 2 determinations 4 h apart or by a diastolic blood pressure >110 mmHg, as well an associated proteinuria of at least 300 mg/24 h after 20 weeks of gestation (6). Early-onset preeclampsia was defined as having symptoms before 34 weeks of pregnancy, whereas late-onset was defined as having symptoms after 34 weeks of …