Prenatal Tobacco and Cannabis Exposure: A Translational Study

这项申请的广泛目标是解决烟草和烟草制品共病使用这一巨大的公共卫生问题， * 利用转化科学，增加对影响机制的了解 人类和动物的协同设计。此应用程序包括一个R21机制，适用于 在妊娠前三个月招募的现有人类样本，并从妊娠至 学龄早期，在儿童中期收集新的数据; R33机制适用于新的 使用动物模型进行研究。人类研究的结果已经并将继续为设计提供信息。 动物模型，并且一起，他们都将告知这个研究计划的下一步。人体研究 将有四组儿童，人口统计学上匹配的对照组，烟草暴露组， 烟草和大麻暴露的儿童，而动物研究将包括轻度和重度暴露组 烟草和大麻以及两者的结合。动物研究将集中在特定的产前 尼古丁（N）和四氢大麻酚（THC）以及N+THC组合在早期 青春期和青年期。有三个具体目标：1）检查体重差异， 影响各组体重的行为，目的是检查产前和产后体重之间的关联。 暴露和肥胖风险; 2）检查认知功能的两个关键方面的差异：注意力和 工作记忆;以及3）检查解释风险的机制，包括胎儿生长不良（人类）、压力 反应性（人和动物）和炎症（人和动物）。这些协同目标将为 更大的研究计划，其长期目标是了解产前暴露对肥胖的影响， 以及代谢紊乱、物质使用和危险行为以及这些高危儿童的过早衰老。 这项转化研究具有很高的影响力，因为它将帮助临床医生制定个性化的治疗计划 这对儿童到成人的健康都有重要影响。

The broad goal of this application is to address the large public health problem of comorbid use of tobacco and cannabis during pregnancy and increase understanding of mechanisms of effect by using translational science with synergistic human and animal designs. This application consists of an R21 mechanism applied to an existing human sample recruited in the first trimester of pregnancy and assessed repeatedly from pregnancy to early school age, with new data to be collected in middle childhood; and an R33 mechanism applied to a new study using an animal model. The results of the human study have and will continue to inform the design of the animal model, and together, they will both inform the next steps in this program of research. The human study will have four groups of children, demographically matched controls, tobacco exposed, and light and heavy tobacco and cannabis exposed children, while the animal study will include light and heavy exposure groups for tobacco and cannabis and the combination of the two. The animal study will focus on the specific prenatal effects of nicotine (N) and Tetrahydrocannabinol (THC), as well as the combination N+THC during early adolescence and young adulthood. There are three specific aims: 1) to examine differences in body weight and behaviors that impact body weight across groups, with the goal of examining associations between prenatal exposure and obesity risk; 2) to examine differences in two critical aspects of cognitive function: attention and working memory; and 3) to examine mechanisms explaining risk including poor fetal growth (human), stress reactivity (human and animal), and inflammation (human and animal). These synergistic aims will then inform the larger program of research with the long term goal of understanding prenatal exposure effects on obesity and metabolic disorders, substance use and risk behaviors, and early aging among these high risk children. This translational study is of high impact in that it will help clinicians to make personalized treatment plans during pregnancy with important implications on childhood through adult health.