(552) Accelerated epigenetic clock aging in peripheral blood is associated with obstetric metabolic syndrome-related outcomes

Epigenetic clocks use CpG DNA methylation (DNAm) to estimate biologic age; acceleration is associated with diabetes mellitus (DM), heart disease, and shorter life. It is unknown if DNAm age is also related to cardiometabolic outcomes in pregnancy. AgeAccelGrim is a novel epigenetic clock that combines 7 DNAm components. We sought to determine if AgeAccelGrim is associated with obstetric metabolic syndrome.


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 DNAm 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 obstetric metabolic syndrome, defined as a diagnosis of hypertension (HTN, including preeclampsia) and/or DM (including GDM). As chronic HTN and Type2 DM are competing diagnoses for obstetric specific disease, gestational and/or pre-gestational timing were permissible. Secondary outcomes were HTN and DM (separately). Values of AgeAccelGrim and its 7 DNAm components were compared by each outcome. Data were analyzed by chi2, t-test, Mann-Whitney, and logistic regression (controlling for maternal age, cell counts, BMI).


Results:

165 patients met inclusion criteria; 80 (48.5%) had obstetric metabolic syndrome; 56/80 (70%) had HTN and 43/80 (54%) had DM; notably, 19/80 (23.8%) met both HTN and DM criteria. Cohort characteristics are shown in Table 1. In unadjusted analyses, AgeAccelGrim was associated with DM only, but DNAm of 6 of 7 epigenetic clock components was higher for those with obstetric metabolic syndrome, Table 2. In regression models, patients with DNAm values above the median for AgeAccelGrim (aOR for DM: 2.50, 95% CI 1.14-5.48) and DNAmPAI1 (aOR for obstetric metabolic syndrome: 3.0, 95% CI 1.5-5.9 and aOR for DM: 4.05, 95% CI 1.8-9.3) had higher risks of HTN and/or DM.


Conclusion:

Accelerated biologic aging is associated with obstetric metabolic syndrome, with effects most notable for current or previous DM.