Pathways linking social disparities, inflammation, and health across generations

描述（由申请人提供）：社会经济地位（SES）的维度被人口和行为科学家认为是疾病的“根本原因”，通过更接近的途径影响个人健康，以及人口健康的差异。炎症是正常免疫功能的重要组成部分，但妊娠期间过度或失调的炎症会导致不良的出生结果，可能会给下一代带来不良的健康轨迹。社会经济因素是炎症变异的重要决定因素，但SES在整个生命过程中的影响途径尚不清楚。该项目的具体目标是：1)验证非临床环境中测量炎症的微创方法；2)研究生命早期（妊娠期、婴儿期）环境对成年期、妊娠期炎症的影响；3)分析妊娠期炎症对分娩结局的预测作用；4)评估炎症基因的表观遗传修饰作为早期生活环境长期影响的机制。该项目侧重于干血点（DBS）——从一个简单的手指棒上采集的全血滴——作为静脉穿刺的一种微创替代方法，有助于以最低的成本或负担从大量人群中采集血液。测量抗炎活性和抗炎活性（细胞因子水平、基因表达模式）的方法将应用于一项大型的、正在进行的出生队列研究，该研究具有30年的前瞻性收集数据。从怀孕第7个月的孕妇中收集DBS样本，并测量炎症模式，以验证生命早期的社会经济地位是成年期妊娠期间炎症调节的重要预测因子的假设。还将研究婴儿期的营养、传染病和社会心理环境，作为介导早期生活SES对成年期炎症影响的中间途径。孕妇将在分娩时进行随访，以调查怀孕期间的炎症是否与早产或后代出生体重较低有关。将测量炎症基因启动子区域甲基化的样本，以研究表观遗传过程是否作为一种机制，通过这种机制，早期生活环境在怀孕期间被“记住”，并塑造下一代的健康。新的微创方法的发展将促进未来基于社区的炎症研究。这项研究的发现将促进对炎症的科学理解，炎症是社会环境导致不良出生结果和生命过程中健康差异的关键途径，并且可能跨越几代人。

DESCRIPTION (provided by applicant): Dimensions of socioeconomic status (SES) are recognized by demographic and behavioral scientists as "fundamental causes" of disease that operate through more proximate pathways to shape individual health, as well as disparities in population health. Inflammation is an important part of normal immune function, but excessive or dysregulated inflammation during gestation contributes to adverse birth outcomes, potentially setting up poor trajectories of health for the next generation. Socio-economic factors are important determinants of variation in inflammation, but the pathways of SES influence across the life course are not known. The specific aims of this project are: 1) To validate minimally-invasive methods for measuring inflammation in non-clinical settings; 2) To investigate how environments in early life (gestation, infancy) influence inflammation in adulthood, during pregnancy; 3) To analyze inflammation during pregnancy as a predictor of birth outcomes; and 4) To evaluate epigenetic modifications to inflammatory genes as a mechanism accounting for long-term effects of early life environments. The project focuses on dried blood spots (DBS) - drops of whole blood collected from a simple finger stick - as a minimally-invasive alternative to venipuncture that facilitates the collection of blood from large numbers of people, at minimal cost or burden. Methods for measuring pro- and anti-inflammatory activity (cytokine levels, patterns of gene expression) will be applied to a large, ongoing birth cohort study with 30 years of prospectively collected data. DBS samples will be collected from pregnant women during the 7th gestational month, and patterns of inflammation measured to test the hypothesis that socioeconomic status early in life is a significant predictor of the regulation of inflammation in adulthood, during pregnancy. Nutritional, infectious disease and psychosocial environments in infancy will also be investigated as intermediate pathways mediating the influence of early life SES on inflammation in adulthood. Pregnant women will be followed up at delivery, to investigate whether inflammation during pregnancy is associated with pre-term delivery or lower offspring birth weight. Samples will be measured for methylation of promoter regions of inflammatory genes to investigate whether epigenetic processes serve as a mechanism through which early life environments are "remembered" during pregnancy and shape the health of the next generation. The development of new, minimally-invasive methods will facilitate future community-based research on inflammation. Findings from the study will advance scientific understanding of inflammation as a key pathway through which social environments contribute to adverse birth outcomes and disparities in health over the life course, and potentially across generations.