Environmental Exposures and Congenital Heart Disease
Environmental Exposures and Congenital Heart Disease
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环境暴露与先天性心脏病
DOI：
10.1542/peds.2021-052151
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发表时间：
2022-01-01
期刊：
影响因子：
8
通讯作者：
Kalfa, David
中科院分区：
文献类型：
--
作者：
Boyd, Rebekah;McMullen, Hannah;Kalfa, David
先天性心脏病(CHD)是世界上最常见的先天性畸形，全球每1000名新生儿中就有8到12名婴儿受到影响，并导致40%的产前死亡。然而，其原因主要仍不清楚，只有高达15%的CHD病例具有确定的遗传原因。探索遗传学和环境暴露之间的复杂关系是理解CHD发展的多因素本质的关键。关于母亲环境暴露及其与冠心病的关系，已经进行了多个人群水平的关联研究，包括评估母亲疾病、药物暴露、环境污染和烟酒使用对冠心病发病率的影响。然而，这些研究都是以孤立的方式进行的，很少研究多种环境暴露之间的相互作用。在这里，我们广泛地和定性地回顾了当前关于母亲和父亲产前暴露及其与CHD的关联的文献。我们建议使用暴露组的新兴领域的框架，即基因组的环境补充，来审查所有内部和外部产前环境暴露，并确定加强或减轻暴露之间的协同作用。最后，我们提出了机制途径，通过产前环境暴露的整体，包括胎盘和心脏发育以及妊娠早期的内部血管和胎盘形态之间的相互作用，可能诱导发生CHD的易感性。
Congenital heart disease (CHD) is the most common congenital abnormality worldwide, affecting 8 to 12 infants per 1000 births globally and causing >40% of prenatal deaths. However, its causes remain mainly unknown, with only up to 15% of CHD cases having a determined genetic cause. Exploring the complex relationship between genetics and environmental exposures is key in understanding the multifactorial nature of the development of CHD. Multiple population-level association studies have been conducted on maternal environmental exposures and their association with CHD, including evaluating the effect of maternal disease, medication exposure, environmental pollution, and tobacco and alcohol use on the incidence of CHD. However, these studies have been done in a siloed manner, with few examining the interplay between multiple environmental exposures. Here, we broadly and qualitatively review the current literature on maternal and paternal prenatal exposures and their association with CHD. We propose using the framework of the emerging field of the exposome, the environmental complement to the genome, to review all internal and external prenatal environmental exposures and identify potentiating or alleviating synergy between exposures. Finally, we propose mechanistic pathways through which susceptibility to development of CHD may be induced via the totality of prenatal environmental exposures, including the interplay between placental and cardiac development and the internal vasculature and placental morphology in early stages of pregnancy.