Epigenomic signatures of accelerated epigenetic aging are associated with congenital heart disease in newborns

ABSTRACT: Background: Congenital heart disease (CHD) lesions are the most common birth defects and are associated with life-long neurodevelopmental risks. The exact mechanism by which CHD and neurodevelopment are linked remains unclear; exploring the epigenome in these cases may provide novel insights into predictive biomarkers contributing to outcomes. The present study characterizes the impact of CHD on the newborn epigenome and uncovers potential differences in epigenetic age that may underpin long-term neurodevelopmental disabilities in this high-risk population. Methods: This is a prospective, single-site case-control study conducted at Children’s National Hospital with subjects enrolled from the Washington DC Metropolitan area. Genomic samples were collected between 2018 and 2024 and analyzed using the Illumina MethylationEPIC BeadChip array platform. PedBE was used to assess infant biological age acceleration. Results: Using a methylation array approach, analysis of 33 newborns with complex CHD requiring neonatal cardiac surgery and 26 healthy controls. There was a significant accelerated epigenetic age in newborns with CHD compared to newborns from uncomplicated pregnancies (p < 0.001). Further subgroup analysis within the CHD cohort revealed that both single- and two-ventricle CHD displayed significant accelerated epigenetic age, with transposition of the great arteries (TGA) cases specifically having the greatest accelerated age (107.2 days, p = 0.0001). Further analysis of the CHD group revealed significant age acceleration associated with low blood oxygen saturation. Conclusions: The present study reveals novel epigenomic signatures newborns with CHD. The functional significance of these findings, specifically accelerated epigenetic age, should be the focus of future analyses to uncover correlations associated with related outcomes. These studies aim to advance our understanding of mechanisms underlying long-term neurodevelopmental and behavioral impairment in these patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE293799 | GEO | 2025/07/09

REPOSITORIES: GEO