Biologic Mechanisms of Labor Dysfunction: A Systems Biology Approach

项目摘要 美国的孕产妇死亡率继续上升，几乎超过了其他所有发达国家。完毕 经历过与怀孕有关的死亡的妇女中，有一半的人在怀孕之前没有可识别的危险因素 劳力。对于这些妇女来说，导致死亡或发病的一连串事件往往始于分娩。 功能障碍。目前关于劳动障碍的生理学决定因素的文献表明，脂毒性 可能是子宫收缩强度和协调性降低的原因。脂肪毒性是一种全系统的 当过多的游离脂肪酸沉积在细胞膜和非脂肪组织中时发生的情况， 导致肥胖和非肥胖女性的慢性炎症和细胞功能障碍。黑人女性是 死于妊娠并发症的可能性是非西班牙裔白人女性的3-4倍， 健康的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。 我们的理论是，血脂水平的变化可能提供了与黑人女性怀孕相关的缺失环节 经历、健康和劳动结果。拟议的研究将使用系统生物学方法来 在妊娠过程中，确定在分娩障碍之前的血脂变化是如何发展的 在独立的生育中心接受产前护理的黑人妇女队列(Aim1)，并测量 这些血脂变化受孕期健康的影响，包括母亲的行为、身体 构成、健康的社会决定因素和血清脂肪组织激素(目标2)。最后，我们会 评估产前护理模式对妊娠健康和妊娠期血脂紊乱的影响 将出生中心队列与在医院接受产前护理的黑人女性队列进行比较(AIM 3)。招募出生中心队列将以保留150名在第一时间开始产前护理的妇女为目标 每三个月进行有计划的问卷调查和采血。分娩完成后，详细图表- 将进行审查，以确定劳工功能障碍比较的病例和比较。为了我们的期末考试 检查产前护理模式对血脂和分娩结局的影响的分析，我们将利用 来自167名围产期水平相似的黑人女性的现有队列的问卷和血脂组学数据 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 然后用来比较不同组之间的血脂特征和怀孕暴露。拟议的研究 研究汇聚了尖端技术和一支拥有劳动科学专长的多学科团队 功能障碍，身体成分测量，全面的营养和体力活动分析， 脂质组学、种族差异调查和系统生物学方法来应对劳动障碍--一个 对产妇发病率和死亡率影响最大的疾病。从这项研究获得的结果将 提供功能信息，使预测劳动功能障碍的生物标志物的识别成为现实 为早期发现、有针对性的干预和预防劳动功能障碍提供了可能性，改变了未来。

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.