Kocher Kristen, Ngwa Julius, Bhattacharya Surajit, Donofrio Mary, Limperopoulos Catherine, Andescavage Nickie
The Developing Brain Institute, Children's National Hospital, Washington, DC, USA.
Center for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA.
BMC Med Genomics. 2025 Jul 28;18(1):121. doi: 10.1186/s12920-025-02189-2.
Congenital heart disease (CHD) lesions are the most common birth defects and despite advances in care, are associated with short- and long-term co-morbidities. The exact mechanisms that may influence outcomes in survivors with CHD remain unclear and are likely multi-factorial; 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 through assessments of epigenetic age.
This is a prospective, single-site case-control pilot 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.
Using a methylation array approach, we analyzed the epigenetic age 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 (+ 72.9 days) compared to newborns from uncomplicated pregnancies (+ 13.9 days, p < 0.001, unadjusted). Further subgroup analysis within the CHD cohort revealed that both single- (+ 56.6 days) and two-ventricle CHD (+ 64.8 days) displayed significant accelerated epigenetic age, with transposition of the great arteries (TGA) cases having the greatest accelerated age (107.2 days, p = 0.0001). Stepwise analysis of clinical measures in the CHD group revealed significant age acceleration was associated with low blood oxygen saturation.
This pilot study reveals accelerated epigenetic aging in newborns with critical CHD compared to healthy controls. Though the mechanisms behind these findings are not well-defined, the association between postnatal measures of oxygen saturation and epigenetic age suggests hypoxia may play a significant role and should be explored in future studies.
先天性心脏病（CHD）病变是最常见的出生缺陷，尽管医疗水平有所进步，但仍与短期和长期合并症相关。影响CHD幸存者预后的具体机制尚不清楚，可能是多因素的；在这些病例中探索表观基因组可能为有助于预后的预测生物标志物提供新的见解。本研究通过评估表观遗传年龄来表征CHD对新生儿表观基因组的影响。
这是一项在儿童国家医院进行的前瞻性、单中心病例对照试点研究，研究对象来自华盛顿特区大都会地区。2018年至2024年期间收集基因组样本，并使用Illumina MethylationEPIC BeadChip阵列平台进行分析。使用PedBE评估婴儿生物学年龄加速情况。
采用甲基化阵列方法，我们分析了33例需要新生儿心脏手术的复杂CHD新生儿和26例健康对照的表观遗传年龄。与正常妊娠新生儿（+13.9天）相比，CHD新生儿的表观遗传年龄显著加速（+72.9天）（未调整，p<0.001）。CHD队列中的进一步亚组分析显示，单心室CHD（+56.6天）和双心室CHD（+64.8天）的表观遗传年龄均显著加速，大动脉转位（TGA）病例的年龄加速最为明显（107.2天，p=0.0001）。对CHD组临床指标的逐步分析显示，显著的年龄加速与低血氧饱和度相关。
这项试点研究表明，与健康对照相比，患有严重CHD的新生儿表观遗传衰老加速。尽管这些发现背后的机制尚不清楚，但出生后血氧饱和度测量与表观遗传年龄之间的关联表明，缺氧可能起重要作用，应在未来研究中进行探索。
