(988) Accelerated epigenetic clock aging in peripheral blood is associated with preterm birth (PTB)

Epigenetic clocks use CpG DNA methylation (DNAm) to estimate biologic age; acceleration is associated with cancer, heart disease, and shorter lifespan. Few studies evaluate DNAm age and pregnancy outcomes. AgeAccelGrim is a novel epigenetic clock that combines 7 DNAm components. We sought to determine if maternal biologic aging (via AgeAccelGrim) is associated with early PTB.


Study Design:

Prospective cohort of patients delivering 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. AgeAccelGrim and its 7 DNAm components were estimated by the Horvath DNAm age online tool. The primary outcome was PTB < 34 wks; secondary outcomes were PTB < 37 and < 28 wks. AgeAccelGrim was considered continuously and by quartiles; exploratory analyses evaluated each DNAm component. Data were analyzed by chi2, t-test, rank-sum, logistic regression (controlling for maternal age, cell counts, low SES, and sample GA), and Kaplan-Meier.


Results:

163 patients met inclusion criteria; 49% delivered < 37, 38% < 34, and 18% < 28 wks. Cohort characteristics are shown in Table 1A. AgeAccelGrim correlated with chronologic maternal age (Rho=0.84, p< 0.001); median acceleration was inversely proportional to each PTB cutoff, including < 37 (+0.40 vs. -0.35 years, p=0.049), < 34 (+0.51 vs. -0.26 years, p=0.036), and < 28 (+1.05 vs. -0.24 years, p=0.001) wks. DNAm of all 7 clock components was higher for those with PTB < 34 wks, but most p=NS, Table 1B. In regression models, patients with the highest quartile AgeAccelGrim values were at higher risk of PTB < 34 (aOR 2.4, 95% CI 1.1-5.1) and < 28 (aOR 3.9, 95% CI 1.6-9.4) wks. In Kaplan-Meier survival analyses, those in the highest AgeAccelGrim quartile delivered earliest (log-rank p< 0.001, Figure 1).


Conclusion:

Accelerated biologic aging is associated with PTB among high-risk patients. Elucidating factors that slow biologic aging may improve birth outcomes.