Abstract P3129: Epigenetic gestational age predicts subclinical atherosclerosis measures from childhood through adulthood

Objective: Atherosclerosis, an aging-related disease, may begin developing in childhood. Epigenetic age is known to predict biological aging accurately, and epigenetic gestational age can predict biological maturity at birth. However, the association of biological aging at birth with atherosclerosis in later life remains unknown. We aim to examine the association of epigenetic gestational age with subclinical measures of atherosclerosis at ages 11 to 24 and their changes over time. Methods: In the Southern California Children’s Health Study, DNA methylation from newborn bloodspots of 242 participants was analyzed using the Infinium 450K array. We calculated epigenetic gestational ages with the Knight and Bohlin algorithms. Intrinsic Epigenetic Gestational Age Deceleration (IEGAD), indicating developmental immaturity at birth, was derived by regressing epigenetic age on clinical gestational age, adjusted for cell composition. Subclinical measures of atherosclerosis, including carotid intima-media thickness (CIMT) and carotid distensibility, were obtained from ultrasound images from all participants in childhood (mean age: 11.3 years, SD: 0.6) in 2007, and repeatedly obtained from a subset of 54 participants again in adulthood (mean age: 24.2 years, SD: 1.6) between 2019 and 2022. Associations between each IEGAD and subclinical atherosclerosis measures, including their changes over time, were evaluated using linear regression, adjusting for sex, race, birthweight, age and body mass index at time of ultrasound, maternal age at delivery, and maternal pregnancy complications. Results: Knight IEGAD (mean: -0.05, SD = 1.1) and Bohlin IEGAD (mean: -0.03, SD=0.78) was moderately correlated (Pearson r = 0.67, P<0.001). Each week increase in Bohlin EEGAD was associated with higher adult CIMT (β = 34.9 µm, 95% CI: 1.63, 68.2) and with more CIMT thickening from childhood to adulthood (β = 2.2 µm/year, 95% CI: 0.05, 4.36). Similarly, each week increase in Knight IEGAD was associated with reduced arterial elasticity, as measured by lower carotid distensibility, in both childhood (β = -3.22, 95% CI: -0.78, -5.67) units (10 −6 ×m 2 /Newtons) and adulthood (β = -1.99, 95% CI: -0.36, 4.34), and an annual reduction of 0.40 (-0.14, 0.94) unit/year from childhood to adulthood. Conclusion: Developmental immaturity at birth, as indicated by epigenetic gestational age, is associated with adverse subclinical atherosclerosis markers from childhood to adulthood.