Prenatal Tobacco and Cannabis Exposure: A Translational Study

修改项目摘要/摘要部分 该申请的广泛目标是解决怀孕期间烟草和大麻共病使用的大公共卫生问题，并通过使用具有协同作用的人类和动物设计的转化科学来增加对效应机制的理解。该应用包括应用于妊娠前三个月招募的现有人类样本的R21机制，并从妊娠到学龄早期进行反复评估，并在儿童中期收集新数据;以及应用于使用动物模型的新研究的R33机制。人类研究的结果已经并将继续为动物模型的设计提供信息，它们将共同为这项研究计划的下一步提供信息。人类研究将有四组儿童，人口统计学匹配的对照组，烟草暴露组，轻度和重度烟草和大麻暴露组，而动物研究将包括烟草和大麻的轻度和重度暴露组以及两者的组合。动物研究将重点关注尼古丁（N）和四氢大麻酚（THC）的特定产前影响，以及青春期早期和成年期早期的N+THC组合。有三个具体目标：1）检查各组之间体重和影响体重的行为的差异，目的是检查产前暴露与肥胖风险之间的关联; 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;和3）检查解释风险的机制，包括胎儿生长不良（人类）、应激反应性（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提供信息，其长期目标是了解产前暴露对肥胖和代谢紊乱，物质使用和风险行为以及这些高危儿童的早期衰老的影响。这项转化研究具有很高的影响力，因为它将帮助临床医生在怀孕期间制定个性化的治疗计划，对儿童到成人的健康产生重要影响。

Modified Project Summary/Abstract Section 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.