Preterm birth (< 37 weeks’ gestation) is a common outcome of pregnancy that has been associated with increased risk of cardiovascular disease for women later in life. Little is known about the physiologic mechanisms underlying this risk. To date, no studies have evaluated if differences in DNA methylation (DNAm) among women who experience preterm birth are short-term or if they persist and are associated with subsequent cardiovascular sequelae or other health disorders. The purpose of this study was to examine long-term epigenetic effects of preterm birth in African American mothers (n = 182) from the InterGEN Study (2014–2019). In this study, we determine if differences in DNAm exist between women who reported a preterm birth in the last 3–5 years compared to those who had full-term births by using two different approaches: epigenome-wide association study (EWAS) and genome-wide co-methylation analyses. Though no significant CpG sites were identified using the EWAS approach, we did identify significant modules of co-methylation associated with preterm birth. Co-methylation analyses showed correlations with preterm birth in gene ontology and KEGG pathways. Functional annotation analysis revealed enrichment for pathways related to central nervous system and sensory perception. No association was observed between DNAm age and preterm birth, though larger samples are needed to confirm this further. We identified differentially methylated gene networks associated with preterm birth in African American women 3–5 years after birth, including pathways related to neurogenesis and sensory processing. More research is needed to understand better these associations and replicate them in an independent cohort. Further study should be done in this area to elucidate mechanisms linking preterm birth and later epigenomic changes that may contribute to the development of health disorders and maternal mood and well-being.

中文翻译：

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InterGEN 研究中有早产史的非裔美国女性的 DNA 甲基化变化

早产（< 37 周妊娠）是妊娠的常见结果，与女性晚年患心血管疾病的风险增加有关。人们对这种风险背后的生理机制知之甚少。迄今为止，尚无研究评估早产妇女的 DNA 甲基化 (DNAm) 差异是短期的，还是持续存在并与随后的心血管后遗症或其他健康障碍相关。本研究的目的是通过 InterGEN 研究（2014-2019 年）检查早产对非裔美国母亲（n = 182）的长期表观遗传效应。在这项研究中，我们使用两种不同的方法确定在过去 3-5 年内报告早产的女性与足月分娩的女性之间是否存在 DNAm 差异：全表观基因组关联研究 (EWAS) 和全基因组共甲基化分析。尽管使用 EWAS 方法没有发现重要的 CpG 位点，但我们确实确定了与早产相关的重要共甲基化模块。共甲基化分析显示基因本体论和 KEGG 通路与早产相关。功能注释分析揭示了与中枢神经系统和感官知觉相关的通路的富集。在 DNAm 年龄和早产之间没有观察到关联，尽管需要更大的样本来进一步证实这一点。我们在非洲裔美国女性出生后 3-5 年发现了与早产相关的差异甲基化基因网络，包括与神经发生和感觉处理相关的通路。需要更多的研究来更好地理解这些关联并将它们复制到一个独立的队列中。应该在这一领域进行进一步的研究，以阐明早产与后期表观基因组变化之间的联系机制，这些变化可能有助于健康障碍的发展以及母亲的情绪和幸福感。