Modeling the Developmental Origins of Adult Disease Risk Factors

描述（由申请人提供）：拟议的研究是结构方程模型的新应用，以确定心血管疾病（CVD）危险因素从产前到青年期发展的复杂途径。这项研究将对成人健康和疾病的发育起源这一日益发展的领域作出重大贡献。该项目使用的数据来自菲律宾宿务一项正在进行的以社区为基础的出生队列研究。宿务纵向健康和营养调查（CLHNS）招募了怀孕期间的妇女，并跟踪调查了从出生到成年的后代。这项为期23年的研究提供了来自大约2000人的无与伦比的健康、营养、社会经济和环境数据。该项目包括对储存的血浆样本进行实验室分析，以确定多种心血管疾病危险因素的水平，包括脂质谱（高、低密度脂蛋白胆固醇、甘油三酯）、炎症标志物（c反应蛋白、促炎细胞因子）和葡萄糖/胰岛素稳态标志物（HOMA胰岛素敏感性和脂联素）。除了血压和肥胖的人体测量指标外，这些指标将成为我们统计模型的结果变量。该项目的核心是开发和估计结构方程模型，这些模型代表了产前和产后营养以及营养相关因素对青年期心血管疾病风险发展的复杂途径。这些模型的主要特点是，它们将允许估计(a)产前暴露的持续直接和间接影响，(b)产前和产后因素的相互作用，以及(c)产后生长轨迹的影响，包括年龄/阶段特定的影响（例如婴儿期、儿童期、青春期）。拟议的研究将通过使用迄今尚未应用于DOHaD范式的方法，并通过探索广泛的相互关联的心血管疾病风险因素，做出重要的方法和实质性贡献。公共卫生相关性：拟议的研究将为我们理解从产前到成年的菲律宾青年队列心血管疾病风险的发育起源做出重要的方法和实质性贡献。

DESCRIPTION (provided by applicant): The proposed research is a novel application of structural equation models to identify the complex pathways through which cardiovascular disease (CVD) risk factors develop from the prenatal period to young adulthood. This research will make a substantial contribution to the growing field of developmental origins of adult health and disease (DOHaD). The project uses data from an ongoing community-based study of a birth cohort from Cebu, Philippines The Cebu Longitudinal Health and Nutrition Survey (CLHNS) recruited women during pregnancy, and has followed the offspring from birth to young adulthood. This 23 year study provides an unparalleled range of health, nutrition, socioeconomic, and environment data from roughly 2,000 individuals. The project includes the laboratory analysis of stored plasma samples to determine levels of multiple CVD risk factors, including lipid profiles (high & low density lipoprotein cholesterol, triglycerides), markers of inflammation (C-reactive protein, pro-inflammatory cytokines) and markers of glucose/insulin homeostasis (HOMA insulin sensitivity and adiponectin). These markers, in addition to blood pressure, and anthropometric indicators of adiposity will be outcome variables for our statistical models. The centerpiece of the project is the development and estimation of structural equation models that represent the complex pathways through which pre- and postnatal nutrition and nutrition-related factors contribute to the development of CVD risk in young adulthood. Key features of these models are that they will allow for the estimation of (a) persistent direct and indirect effects of prenatal exposures, (b) interactions of pre and postnatal factors, and (c) the effects of postnatal growth trajectories, including age/stage-specific effects (e.g. infancy, childhood, adolescence). The proposed research will make important methodological as well as substantive contributions by using methods that have not heretofore been applied to the DOHaD paradigm and by exploring a wide range of interrelated CVD risk factors. PUBLIC HEALTH RELEVANCE: The proposed research will make important methodological and substantive contributions to our understanding of the developmental origins of cardiovascular disease risk in a cohort of Filipino young adults followed from the prenatal period to adulthood.