Preterm Birth (PTB) accounts for approximately 11% of all births worldwide each year and is a profound physiological stressor in early life. The burden of neuropsychiatric and developmental impairment is high, with severity and prevalence correlated with gestational age at delivery. PTB is a major risk factor for the development of cerebral palsy, lower educational attainment and deficits in cognitive functioning, and individuals born preterm have higher rates of schizophrenia, autistic spectrum disorder and attention deficit/hyperactivity disorder. Factors such as gestational age at birth, systemic inflammation, respiratory morbidity, sub-optimal nutrition, and genetic vulnerability are associated with poor outcome after preterm birth, but the mechanisms linking these factors to adverse long term outcome are poorly understood. One potential mechanism linking PTB with neurodevelopmental effects is changes in the epigenome. Epigenetic processes can be defined as those leading to altered gene expression in the absence of a change in the underlying DNA sequence and include DNA methylation/hydroxymethylation and histone modifications. Such epigenetic modifications may be susceptible to environmental stimuli, and changes may persist long after the stimulus has ceased, providing a mechanism to explain the long-term consequences of acute exposures in early life. Many factors such as inflammation, fluctuating oxygenation and excitotoxicity which are known factors in PTB related brain injury, have also been implicated in epigenetic dysfunction. In this review, we will discuss the potential role of epigenetic dysregulation in mediating the effects of PTB on neurodevelopmental outcome, with specific emphasis on DNA methylation and the α-ketoglutarate dependent dioxygenase family of enzymes.

中文翻译：

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早产和神经发育障碍的风险 - 表观遗传失调是否有影响？

每年，早产 (PTB) 约占全球新生儿总数的 11%，是生命早期的一个严重的生理压力源。神经精神和发育障碍的负担很高，其严重程度和患病率与分娩胎龄相关。PTB 是脑瘫、受教育程度较低和认知功能缺陷的主要危险因素，早产儿患精神分裂症、自闭症谱系障碍和注意力缺陷/多动障碍的比例较高。出生胎龄、全身炎症、呼吸道疾病、营养不良和遗传脆弱性等因素与早产后不良结局相关，但将这些因素与不良长期结局联系起来的机制尚不清楚。将 PTB 与神经发育影响联系起来的一种潜在机制是表观基因组的变化。表观遗传过程可以定义为在基本 DNA 序列不发生变化的情况下导致基因表达改变的过程，包括 DNA 甲基化/羟甲基化和组蛋白修饰。这种表观遗传修饰可能容易受到环境刺激的影响，并且在刺激停止后，变化可能会持续很长时间，这提供了一种机制来解释生命早期急性暴露的长期后果。许多因素，如炎症、氧合波动和兴奋性毒性，这些都是 PTB 相关脑损伤的已知因素，也与表观遗传功能障碍有关。在这篇综述中，我们将讨论表观遗传失调在介导 PTB 对神经发育结果影响中的潜在作用，特别强调 DNA 甲基化和 α-酮戊二酸依赖性双加氧酶家族。