Prenatal Tobacco Exposure: Perinatal and Genetic Risks

描述（由申请人提供）：怀孕期间使用烟草的妇女比使用任何其他物质的妇女都多，但对烟草对人类早期发育的影响知之甚少。产前烟草暴露是导致低出生体重和早产的最大可预防风险因素，导致医疗保健费用增加。尼古丁通过影响神经递质系统直接作用于发育中的胎儿神经系统，并通过胎盘血流的血管收缩间接作用于发育中的胎儿神经系统。在动物中，产前尼古丁暴露通过改变多巴胺和乙酰胆碱活性过早地发出细胞分化的信号，导致细胞发育中断、细胞数量减少和突触连接异常，对多巴胺能系统的影响尤其显著。由于多巴胺能系统与婴儿、儿童和成人的运动、注意力和气质行为有关，这些行为特别容易受到产前烟草暴露的干扰。由于脆弱的神经系统，早产儿产前烟草暴露的额外风险可能是双重有害的。另外，早产通常会缩短妊娠晚期子宫内暴露的持续时间，减弱产前烟草暴露的影响。最后，导致多巴胺能活性净减少的特定基因变异可能使这些婴儿更容易受到产前烟草暴露影响。这项研究将探讨产前烟草暴露的影响，作为围产期风险和遗传脆弱性的函数，同时考虑到社会环境。将招募大量早产儿和足月儿样本（n = 360）（早产儿和暴露水平的过采样），并根据背景特征进行仔细选择，以最大限度地提高烟草相关差异。全面的母亲访谈和可替宁水平的生化分析（母亲和婴儿尿液，婴儿胎粪）将用于测量产前烟草暴露。除了酒精、咖啡因和其他物质暴露外，产后烟草暴露也将通过同样全面的多种方法进行测量。将对新生儿结局进行纵向评估，以更可靠地确定对早期发育的影响;无论是在产后暴露和社会环境影响最小的医院，还是在这些影响更突出的出院后。多种方法被用来评估不同的新生儿结果域，与工具，捕捉年龄依赖性的神经行为技能和身体发育。先进的统计方法将揭示产前烟草暴露对发育过程的影响，包括水平和生长速度。

DESCRIPTION (provided by applicant): More women use tobacco during pregnancy than any other substance, yet little is known about the effects of on early human development. Prenatal tobacco exposure is the single largest preventable risk factor for low birth weight and prematurity, resulting in increased healthcare costs. Nicotine acts on the developing fetal nervous system directly through effects on neurotransmitter systems and indirectly by vasoconstriction of placental blood flow. In animals, prenatal nicotine exposure prematurely signals cell differentiation by altered dopamine and acetylcholine activity that results in disrupted cell development, reduced cell number, and aberrant synaptic connections, with particularly marked effects on dopaminergic systems. Because dopaminergic systems are related to motor, attention, and temperament behavior in infants, children, and adults, these behaviors are particularly susceptible to disruption by prenatal tobacco exposure. Because of the vulnerable nervous system, the added risk of prenatal tobacco exposure in preterm infants may be doubly deleterious. Alternatively, preterm birth typically shortens the duration of in utero exposure in the third trimester, with attenuated prenatal tobacco exposure effects. Finally, specific gene variants that result in net reductions in dopaminergic activity may render these infants more vulnerable to prenatal tobacco exposure effects. This study will examine the effects of prenatal tobacco exposure as a function of perinatal risk and genetic vulnerability, while accounting for the social environment. A large sample of preterm and full term infants (n = 360) will be recruited (with oversampling on prematurity and exposure level) and carefully selected on background characteristics to maximize tobacco exposure-related differences. Thorough maternal interviews and biochemical analysis of cotinine level (maternal and infant urine, infant meconium) will be used to measure prenatal tobacco exposure. Postnatal tobacco exposure, in addition to alcohol, caffeine, and other substance exposure, also will be measured through similarly thorough multi-methods. Neonatal outcome will be assessed longitudinally to more reliably determine effects on early development; both in the hospital where the effects of postnatal exposure and social environment are minimized, and after discharge where these effects are more prominent. Multiple methods are used to assess different neonatal outcome domains, with instruments that capture age-dependent neurobehavioral skill and physical growth. Sophisticated statistical methods will uncover prenatal tobacco exposure effects on developmental processes, including level and growth rates.