(1169) DNA methylation-estimated blood cell immune subtypes in early pregnancy are associated with preterm birth (PTB)

Advanced algorithms can use CpG DNA methylation (DNAm) data to estimate blood cell types associated with immune system function, producing results highly correlated to flow cytometry. We sought to determine if DNAm-estimated blood cell abundance is associated with PTB.


Study Design:

Prospective cohort of patients at a tertiary University hospital with singleton gestations, at high risk for spontaneous PTB, and a blood sample obtained < 28 wks’. Genome-wide CpG methylation was measured using the Illumina® EPIC BeadChip. The abundance of 7 immune-related cells (CD4+T, CD8+T, B cells, granulocytes, monocytes, NK cells, and plasma blasts) was estimated using the advanced options of the Horvath DNAm age online tool. The primary outcomes were PTB < 37, < 34, and < 28 wks. Cell values were considered continuously and were dichotomized whereby quartile 4 (Q4) was compared to Q1-3. Data were analyzed by chi2, t-test, and logistic regression (controlling for GA at blood sample, low SES, and hx of PTB).


Results: 163 patients met inclusion criteria; 48% delivered < 37, 39% < 34, and 21% < 28 wks (Table 1A). Several blood cell parameters were associated with PTB, particularly < 34 and < 28 wks. Mean NK, CD4+T, and CD8+T cell counts declined with each PTB cutoff and were lowest among those delivering < 28 wks (Table 1B). Conversely, mean counts of granulocytes and plasma blast cells increased with each PTB cutoff (Table 1B).  In regression models, patients with B-cells in Q4 had a higher aOR of PTB < 37 wks, those with granulocytes, monocytes, and CD4+T in Q4 had a higher aOR of PTB < 34 wks, and patients with granulocytes, CD4+T, plasma blasts, and CD8+T cells in Q4 had a higher aOR of PTB < 28 wks compared to individuals with values in Q1/Q2/Q3, Figure 1.

Conclusion:

Among high-risk patients, distinct differences in the abundance of immunity-related peripheral blood cells are appreciated in early pregnancy among patients who deliver preterm vs those that do not.