Pathways linking social disparities, inflammation, and health across generations

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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.