Nearly 1.3 million cesareans are performed each year, resulting in the birth of one third of all children nationwide. When indicated, cesarean sections reduce morbidity and mortality to mother and fetus. However, many cesareans do not have a clear medical indication leading to an increase in serious maternal and perinatal morbidity and mortality. Increasing evidence also suggests that risks to offspring may extend to chronic-non communicable conditions. Consistent evidence shows that individuals born by cesarean are at an increased risk of obesity as children and that higher rates of obesity persist through adult life, raising the possibility that the long-term health consequences of being born by cesarean may extend to an increased risk of obesity-related chronic conditions including common cancers (breast, prostate, colorectal), cardiovascular disease and type 2 diabetes. However, data on the association of birth by cesarean with risk factors for or biomarkers of chronic disease risk remains scarce. There is also a paucity of information regarding the biologic mechanisms underlying the relation between cesarean delivery and offspring chronic disease risk. This proposal addresses these knowledge gaps. Specifically, we propose to evaluate the relation of birth by cesarean with pubertal onset ?an established risk factor for breast cancer; with longitudinal trajectories in biomarkers of chronic disease risk ?including markers of mitogenesis, inflammation, insulin resistance, lipid metabolism and adipose tissue activity; and with longitudinal trajectories in body composition (Aims 1 and 2). In addition, we propose to evaluate the relation of birth by cesarean section with longitudinal trajectories in whole genome DNA methylation patterns and gut microbiome (Aims 3 and 4) in order to gain further understanding on the biological underpinnings of the long-term health consequences of birth by cesarean.
One third of all children in the United States are born by cesarean delivery and leading professional organizations believe many of these cesareans do not have a clear medical indication. Increasing evidence suggests that individuals born by cesarean are at an increased risk of obesity as children, adolescents and young adults but it is currently not clear whether this increased risk of obesity results in higher risk of obesity related conditions. We propose to address this issue by evaluating the association between birth by cesarean section with known risk factors for chronic disease risk, including longitudinal trajectories in risk biomarkers, and to gain further insights into the biological underpinnings of these relations by evaluation how cesarean delivery impacts longitudinal trajectories in whole genome DNA methylation patterns and gut microbiota patterns.