New-onset postpartum preeclampsia: epigenetic mechanism and prediction
Kim SK, Vishweswaraiah S, Macknis J, Yilmaz A, Lalwani A, Mishra NK, Guda C, Ogunyemi D, Radhakrishna U, and Bahado-Singh RO. New-onset postpartum preeclampsia: epigenetic mechanism and prediction. J Matern Fetal Neonatal Med 2021.
The journal of maternal-fetal & neonatal medicine
OBJECTIVE: Placental cytosine (CpG) methylation was measured to predict new-onset postpartum preeclampsia (NOPP) and interrogate its molecular pathogenesis.
METHODS: NOPP was defined as patients with a new diagnosis of postpartum preeclampsia developing ≥48 h to ≤6 weeks after delivery with no prior hypertensive disorders. Placental tissue was obtained from 12 NOPP cases and 12 normotensive controls. Genome-wide individual cytosine (CpG) methylation level was measured with the Infinium MethylationEPIC BeadChip array. Significant differential methylation (NOPP vs. controls) for individual CpG loci was defined as false discovery rate (FDR)
RESULTS: There were 537 (in 540 separate genes) significantly (FDR p<.05 with a ≥ 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.
ePub ahead of print