New-onset postpartum preeclampsia: epigenetic mechanism and prediction

OBJECTIVE: Placental cytosine (CpG) methylation was measured to predict new-onset postpartum preeclampsia (NOPP) and interrogate its molecular pathogenesis. METHODS: value <.05. Gene functional enrichment using Qiagen's ingenuity pathway analysis (IPA) was performed to help elucidate the molecular pathogenesis of NOPP. A logistic regression model for NOPP prediction based on the methylation level in a combination of CpG loci was generated. The area under the receiver operating characteristic curves (AUC [95% CI]) sensitivity, and specificity for NOPP prediction based on the CpG methylation level was calculated for each locus. RESULTS: ≥ 2.0-fold methylation difference) differentially methylated CpG loci between the groups. A total of 143 individual CpG markers had excellent individual predictive accuracy for NOPP prediction (AUC ≥0.80), of which 14 markers had outstanding accuracy (AUC ≥0.90). A logistic regression model based on five CpG markers yielded an AUC (95% CI)=0.99 (0.95-0.99) with sensitivity 95% and specificity 93% for NOPP prediction. IPA revealed dysregulation of critical pathways (e.g., angiogenesis, chronic inflammation, and epithelial-mesenchymal transition) known to be linked to classic preeclampsia, in addition to other previously undescribed genes/pathways. CONCLUSIONS: There was significant placental epigenetic dysregulation in NOPP. NOPP shared both common and unique molecular pathways with classic preeclampsia. Finally, we have identified novel potential biomarkers for the early post-partum prediction of NOPP.