Social adversity, gestational stress physiology, and birth outcomes in Hispanic Americans

项目总结/摘要 本项目针对肥胖和2型糖尿病（T2 DM）发病率增加的流行病学观察结果 跨越几代西班牙裔美国人。我们提出了一个新的假设来理解这种现象的基础上， 胎儿编程的概念，健康的社会决定因素，以及生活经验的生物嵌入。证据 表明胚胎/胎儿阶段的生活是一个关键的窗口，在此期间，扰动在子宫内 生物化学环境影响身体组织模式和代谢功能的发展，影响个体的 终身健康和易患肥胖症和T2 DM。我们认为西班牙裔美国人的社会和文化压力 移民妇女可能会影响压力生物学的方式，对怀孕的妇女来说， 发育中的胚胎/胎儿所暴露的环境。西班牙裔移民是一个特别弱势的群体。 易受高度社会逆境影响的群体。我们提出了最初的假设，怀孕的西班牙裔 移民妇女所感受到的社会逆境可能会改变与压力相关的生物过程，从而影响肥胖 和代谢表型，从而使后代易患肥胖症的终身风险增加， 2型糖尿病。在一项对100名怀孕的西班牙裔移民妇女进行的前瞻性纵向研究中， 我们将通过一系列原始的开放式问题、Likert量表项目和经过验证的 问卷调查，并将这些结构与从两个时间点收集的生物样品评估的应激生物学相关， 新生儿体重指数（BMIP）。新生儿的体型与 儿童和成年期肥胖和代谢风险。在这方面，我们将追求两个具体目标。在目标1中，我们 研究孕妇如何感知社会逆境（移民相关的创伤，政治受害， 辨别）涉及妊娠应激生理学的四个领域：下丘脑-垂体-肾上腺-胎盘， 炎症、代谢和氧化。在目标2中，我们将研究孕妇对社会逆境的感知如何 与新生儿BMIP有关。PI在社会文化结构的理论和分析技术方面获得的专业知识， 母亲-胎盘-胎儿生物学，肥胖症和新陈代谢在她的K 01培训和研究使她独特地适合 成功实现R 03目标。她的K 01项目关注的是文化适应可能会影响 妊娠生物学，在R 03提案中通过评估社会文化压力的其他方面， 更全面地描述妊娠应激生理学，重要的是，直接测量儿童结局。 这些努力将为R 01提案奠定基础，该提案将使PI成为完全独立的研究者。 最终，这些分析可能会揭示关于社会逆境经历如何促进慢性病的新信息。 疾病状态不仅在患病个体中，而且在几代人中。理解社会、 少数民族健康差异的文化和生物机制可能揭示了新的社会，文化或生物目标， 采取干预措施，以减少少数群体社区的不利处境和健康状况不佳的代际循环。这个项目 强调对女孩和妇女福祉的投资可能有助于缓解健康差距。

PROJECT SUMMARY/ABSTRACT This project addresses the epidemiological observation of increasing rates of obesity and type-2 diabetes mellitus (T2DM) across generations of Hispanic Americans. We propose a novel hypothesis to understand this phenomenon based on the concepts of fetal programming, social determinants of health, and biological embedding of life experience. Evidence suggests that the embryonic/fetal phase of life represents a critical window during which perturbations in the intrauterine biochemical environment affect development of body tissue patterning and metabolic function, influencing an individual’s lifelong health and susceptibility to obesity and T2DM. We posit that social and cultural stressors among Hispanic immigrant women may influence stress biology in ways that—for women who become pregnant—alter the biochemical environment to which the developing embryo/fetus is exposed. Hispanic immigrants are an exceptionally disadvantaged group who are vulnerable to high degrees of social adversity. We propose the original hypothesis that pregnant, Hispanic immigrant women’s perceived social adversity may alter stress-related biological processes to influence adiposity and metabolic phenotypes in the fetus, thereby pre-disposing the offspring to enhanced lifelong risk of obesity and T2DM. In a prospective, longitudinal study of 100 pregnant, Hispanic immigrant women established with the PI’s K-award, we will assess perceived social adversity from a series of original open-ended questions, Likert-scale items, and validated questionnaires, and relate these constructs to stress biology assessed from biosamples collected at two timepoints during pregnancy, and newborn body mass index percentiles (BMIP). Newborn body size has well-established correlations with childhood and adulthood adiposity and metabolic risk. In this context, we will pursue two specific aims. In Aim 1, we will examine how pregnant women’s perceived social adversity (immigration-related trauma, political victimization, discrimination) relates to four domains of gestational stress physiology: hypothalamic-pituitary-adrenal-placental, inflammatory, metabolic, and oxidative. In Aim 2, we will examine how pregnant women’s perceived social adversity relates to newborn BMIP. The expertise the PI gained in theory and analytic techniques for socio-cultural constructs, maternal-placental-fetal biology, adiposity and metabolism in her K01 training and research make her uniquely suited to successfully execute the R03 aims. Her K01 project, which focused on the possibility that acculturation may influence gestational biology, is logically extended in this R03 proposal by assessing other dimensions of socio-cultural stress, characterizing gestational stress physiology more comprehensively, and, importantly, directly measuring child outcomes. These endeavors will lay the foundation for an R01 proposal that will establish the PI as a fully independent investigator. Ultimately, these analyses may reveal new information about how experiences of social adversity can promote chronic disease states not only in the afflicted individuals but also across generations. Understanding the interplay between social, cultural, and biological mechanisms in minority health disparities may reveal new social, cultural, or biological targets of intervention to diminish inter-generational cycles of disadvantage and poor health in minority communities. This project emphasizes the possibility that investment in the well-being of girls and women can help alleviate health disparities.