Utilization of Epigenome-wide DNA Methylation for Longitudinal Comparison of White Blood Cell Proportions Across Preeclamptic and Normotensive Pregnancy by Self-Reported Race

Objective We utilized epigenome-wide DNA methylation data to estimate/compare white blood cell (WBC) proportions in plasma across preeclamptic (case) and uncomplicated, normotensive (control) pregnancy. Methods We previously collected methylation data using Infinium® MethylationEPIC Beadchips during the three trimesters in 28 cases and 28 controls (21 Black, 7 White participants/group). We employed Houseman’s regression calibration method to estimate and compare neutrophil, monocyte, B cell, NK cell, CD4+ T and CD8+ T cell proportions across pregnancy and between cases and controls. Results We observed changes in WBC proportions across pregnancy within cases and controls that varied by cell type and race. Neutrophils represented the largest WBC mean proportion in all three trimesters for cases (Mean±SD: 67.2±9.6% – 74.4±12%) and controls (64.2±11% – 74.0±7.9%). Mean B cell proportions were significantly lower in cases than controls in Trimester 1 (5.25±0.02% versus 6.30±0.02%, p =0.02). The remaining mean cell proportions did not significantly differ in the overall sample. Stratified analyses revealed race-specific differences. In White participants (n=14): (1) neutrophil proportions were significantly higher in cases in Trimester 1 ( p =0.04), but significantly lower in Trimester 2 ( p =0.02), (2) B cell proportions were significantly lower in cases in Trimester 1 ( p =0.001). No significant differences were detected among Black participants (n=42). Conclusions Although chronic inflammation characterizes preeclampsia, few studies have investigated WBCs across pregnancy. We report differences between cases and controls across pregnancy. Our findings in a small sample demonstrate the need for additional studies investigating the relationship between race and WBCs in pregnancy, which could provide insight into preeclampsia pathophysiology.