Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, North Carolina.
Birth Defects Res. 2019 Oct 15;111(17):1259-1269. doi: 10.1002/bdr2.1550. Epub 2019 Jul 16.
Maternal smoking causes lower birth weight, birth defects, and other adverse pregnancy outcomes. Epidemiological evidence over the past four decades has grown stronger and the adverse outcomes attributed to maternal smoking and secondhand smoke exposure have expanded. This review presents findings of latent and persistent metabolic effects in offspring of smoking mothers like those observed in studies of maternal undernutrition during pregnancy. The phenotype of offspring of smoking mothers is like that associated with maternal undernutrition. Born smaller than offspring of nonsmokers, these children have increased risk of being overweight or obese later. Plausible mechanisms include in utero hypoxia, nicotine-induced reductions in uteroplacental blood flow, placental toxicity, or toxic growth restriction from the many toxicants in tobacco smoke. Studies have reported increased risk of insulin resistance, type 2 diabetes and hypertension although the evidence here is weaker than for overweight/obesity. Altered DNA methylation has been consistently documented in smoking mothers' offspring, and these epigenetic alterations are extensive and postnatally durable. A causal link between altered DNA methylation and the phenotypic changes observed in offspring remains to be firmly established, yet the association is strong, and mediation analyses suggest a causal link. Studies examining expression patterns of affected genes during childhood development and associated health outcomes should be instructive in this regard. The adverse effects of exposure to tobacco smoke during pregnancy now clearly include permanent metabolic derangements in offspring that can adversely affect life-long health.
母亲吸烟会导致婴儿出生体重降低、出生缺陷和其他不良妊娠结局。过去四十年的流行病学证据不断增强，与母亲吸烟和二手烟暴露相关的不良后果也在不断扩大。本综述介绍了吸烟母亲对后代潜在和持续的代谢影响的研究结果，这些影响类似于怀孕期间母亲营养不良的研究中观察到的结果。吸烟母亲的后代表型与与母亲营养不良相关的表型相似。这些孩子出生时比不吸烟母亲的孩子小，以后超重或肥胖的风险增加。合理的机制包括宫内缺氧、尼古丁引起的子宫胎盘血流减少、胎盘毒性或烟草烟雾中许多有毒物质引起的毒性生长受限。研究报告称，胰岛素抵抗、2 型糖尿病和高血压的风险增加，尽管这里的证据比超重/肥胖弱。在吸烟母亲的后代中，一致记录到 DNA 甲基化改变，这些表观遗传改变广泛且在出生后持久。改变的 DNA 甲基化与后代观察到的表型变化之间的因果关系仍有待确定，但关联非常强，中介分析表明存在因果关系。在儿童发育期间检查受影响基因的表达模式以及相关健康结果的研究应该对此有所启发。怀孕期间接触烟草烟雾的不良影响现在显然包括后代的永久性代谢紊乱，这可能会对终生健康产生不利影响。
