Biologic Mechanisms of Labor Dysfunction: A Systems Biology Approach

项目摘要 美国的孕产妇死亡率持续上升，几乎超过了其他所有发达国家。超过 经历与怀孕有关的死亡的妇女中有一半在怀孕前没有可识别的风险因素， 劳动对这些妇女来说，以死亡或发病告终的一连串事件往往始于分娩 功能障碍目前关于分娩功能障碍的生理决定因素的文献表明， 可能是子宫收缩力和协调性下降的原因脂毒性是一个系统性的 当过量的游离脂肪酸沉积在细胞膜和非脂肪组织中时发生的病症， 引起肥胖和非肥胖妇女的慢性炎症和细胞功能障碍。黑人女性 3-4死于妊娠并发症的可能性是非西班牙裔白色妇女的两倍， 健康决定因素似乎增加了她们在怀孕期间经历新陈代谢变化的风险。 我们推测，血脂谱的改变可能提供了一个连接黑人妇女怀孕的缺失环节， 经验，健康和劳动成果。拟议的研究将使用系统生物学方法， 确定分娩功能障碍之前的脂质变化如何在妊娠过程中发展， 在一个独立的分娩中心（Aim1）接受产前护理的黑人妇女队列，并测量 这些脂质变化受妊娠健康的影响，包括母亲的行为，身体 健康的社会决定因素和血清脂肪组织激素（目标2）。最后我们将 评估产前护理模式对妊娠健康和妊娠期间血脂紊乱的影响， 比较出生中心队列与在医院接受产前护理的黑人妇女队列（Aim 3）。出生中心队列的招募目标是保留150名开始产前护理的妇女， 三个月进行计划的问卷调查和采血。完成劳动后，详细图表- 将进行审查，以确定分娩功能障碍比较的病例和比较。期末 分析检查产前护理模式对血脂和分娩结局的影响，我们将利用 调查问卷和脂质组学数据来自现有的167名黑人妇女的队列， 在附近医院诊所接受产前护理的出生中心队列的风险。差分分析将 然后用于比较各组之间的脂质特征和妊娠暴露。拟议研究 研究汇集了尖端技术和多学科团队与劳动科学专业知识 功能障碍，身体成分测量，全面的营养和身体活动分析， 脂质组学、种族差异调查和系统生物学方法来应对分娩功能障碍--其中之一 对孕产妇发病率和死亡率影响最大的条件。从这项研究中获得的结果将 提供功能信息，使预测分娩功能障碍的生物标志物的鉴定成为真实的 可能性，改变未来的早期发现，有针对性的干预和预防劳动功能障碍。

Project Abstract Maternal mortality in the US continues to rise, outpacing rates in nearly every other developed country. Over half of women who experience pregnancy-related death do not have risk factors that are identifiable prior to labor. For these women, the cascade of events ending in death or morbidity often begins with labor dysfunction. Current literature on the physiologic determinants of labor dysfunction suggests that lipotoxicity may account for decreased uterine contractile strength and coordination. Lipotoxicity is a system-wide condition occurring when excess free fatty acids are deposited in cellular membranes and non-adipose tissues, causing chronic inflammation and cellular dysfunction in both obese and non-obese women. Black women are 3-4 times more likely to die of pregnancy complications than non-Hispanic white women, and social determinants of health appear to increase their risk of experiencing changes in metabolism during pregnancy. We theorize that alterations in lipid profiles may provide a missing link connecting Black women's pregnancy experiences, health, and labor outcomes. The proposed study will use a systems biology approach to determine how the lipid changes that precede labor dysfunction develop over the course of pregnancy in a cohort of Black women receiving prenatal care in a freestanding birth center (Aim1), and measure the extent to which these lipid changes are influenced by pregnancy health, including maternal behaviors, body composition, social determinants of health, and serum adipose tissue hormones (Aim 2). Finally, we will evaluate the influence of prenatal model of care on pregnancy health and lipid perturbations during pregnancy, comparing the birth center cohort to a cohort of Black women receiving prenatal care in a hospital setting (Aim 3). Recruitment of the birth center cohort will target retention of 150 women who begin prenatal care in first trimester for planned questionnaire and blood collections. Following the completion of labor, detailed chart- review will be performed to identify cases and comparisons for labor dysfunction comparisons. For our final analyses examining the influence of prenatal model of care on lipids and labor outcomes, we will leverage questionnaire and lipidomics data from an existing cohort of 167 Black women with similar levels of perinatal risk to the birth center cohort who received prenatal care in nearby hospital clinics. Differential analysis will then be used to compare lipid features and pregnancy exposures between groups. The proposed research study brings together cutting-edge technology and a multi-disciplinary team with scientific expertise in labor dysfunction, body composition measurement, comprehensive nutritional and physical activity analysis, lipidomics, racial disparities investigations, and systems biology approaches to confront labor dysfunction--one of the most impactful conditions affecting maternal morbidity and mortality. Results obtained from this study will provide functional information to make the identification of biomarkers that predict labor dysfunction a real possibility, changing the future for early detection, targeted intervention, and prevention of labor dysfunction.