Association of fetal-derived hypermethylated RASSF1A concentration in placenta-mediated pregnancy complications

Objectives: To assess whether fetal-derived hypermethylated RASSF1A concentrations in maternal plasma during pregnancy are altered in pregnancies associated with placental dysfunction manifested by intrauterine growth restriction (IUGR), preeclampsia (PE), or placental previa (PP) and whether this alteration can be detected in susceptible subjects before the onset of clinical disease. Methods: We performed a real-time quantitative polymerase chain reaction to quantify RASSF1A concentrations before and after methylation-sensitive restriction digestion in maternal plasma at 7-41 gestational weeks of normal pregnancies (n = 161), IUGR (n = 43), PE (n = 22), PP (n = 14) and nonpregnant women (n = 20). Results: A positive correlation was observed between fetal-derived hypermethylated RASSF1A concentration and gestational age for all study groups (r = 0.624, p < 0.001 for IUGR; r = 0.381, p = 0.042 for PE; r = 0.697, p < 0.001 for PP; r = 0.560, p < 0.001 for controls). The concentration of hypermethylated RASSF1A was relatively high at 7-14 gestational weeks in all patient groups. Hypermethylated RASSF1A concentration at 15-28 weeks was significantly higher in patients who subsequently developed IUGR (p = 0.002), PE (p < 0.001) or PP (p < 0.001) than in controls. Conclusion: We first demonstrated increased concentration of fetal-derived hypermethylated RASSF1A sequences according to advancing gestation and before the onset of the clinical manifestation of pregnancy complications secondary to placental dysfunction, such as IUGR, PE and PP. Hypermethylated RASSF1A in maternal plasma may be useful as a potential biomarker to detect placental-mediated pregnancy complications, regardless of fetal gender and polymorphism. (C) 2012 Elsevier Ltd. All rights reserved.