Biologic Mechanisms of Labor Dysfunction: A Systems Biology Approach

分娩功能障碍的生物学机制：系统生物学方法

基本信息

批准号：
10626973
负责人：
Nicole S. Carlson
金额：
$ 38.85万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-27 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10626973
关键词：
Adipose tissue Affect Animals Anxiety Behavioral Biological Birth Birthing Centers Black Populations Black race Blood Blood specimen Body Composition Body fat Body mass index Caring Cell membrane Cellular Membrane Cesarean section Cessation of life Chronic Clinics and Hospitals Collection Consumption Data Deposition Developed Countries Diet Discrimination Disparity Early Diagnosis Event Exhibits Fatty Acids Fatty acid glycerol esters Fiber First Pregnancy Trimester Functional disorder Future Health Health Promotion Hormones Hospitals Individual Induced Labor Inflammation Injury Insulin Resistance Intake Intervention Investigation Labor Onset Late pregnancy Leptin Life Style Link Lipids Literature Maternal Behavior Maternal Mortality Measurement Measures Mental Depression Metabolic Metabolic Pathway Metabolism Midwife Modeling Morbidity - disease rate Non obese Nonesterified Fatty Acids Not Hispanic or Latino Nutritional Obesity Outcome Pathway Analysis Pathway interactions Pattern Perinatal Physical activity Physiological Physiology Polyunsaturated Fatty Acids Postpartum Period Pregnancy Pregnancy Complications Pregnancy Outcome Prenatal care Prevention Questionnaires Recovery Risk Risk Factors Serum Stress Stressful Event System Systems Biology Technology Third Pregnancy Trimester Time Tissues United States Uterine Contraction Uterus Woman Work adiponectin biomarker identification black women cohort early pregnancy electric impedance experience health disparity hospital care improved lipid metabolism lipidomics maternal morbidity maternal obesity multidisciplinary neighborhood safety neonate nutrition perceived discrimination perceived stress predictive marker pregnancy health pregnancy related death prenatal prenatal influence racial disparity recruit research study social health determinants subcutaneous theories

项目摘要

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.

项目摘要美国的孕产妇死亡率继续上升，几乎在其他每个发达国家中都超过了率。超过一半经历了与怀孕有关的妇女的妇女没有可识别的危险因素劳动。对于这些妇女来说，以死亡或发病率结尾的一系列事件通常始于劳动功能障碍。有关劳动功能障碍的生理决定因素的当前文献表明脂肪毒性可能是子宫收缩力和协调的降低。脂肪毒性是整个系统范围的当过量的游离脂肪酸沉积在细胞膜和非掺杂组织中时，发生的情况是引起肥胖和非肥胖女性的慢性炎症和细胞功能障碍。黑人妇女是死于怀孕并发症的可能性是非西班牙裔白人妇女的3-4倍，社会健康的决定因素似乎增加了他们在怀孕期间经历新陈代谢变化的风险。我们认为脂质轮廓的改变可能会提供连接黑人妇女怀孕的缺失链接经验，健康和劳动成果。拟议的研究将使用系统生物学方法来确定在劳动功能障碍之前的脂质变化如何在妊娠过程中发展在独立出生中心（AIM1）接受产前护理的黑人妇女队列（AIM1），并衡量这些脂质变化受妊娠健康的影响，包括孕产妇行为，身体组成，健康的社会决定因素和血清脂肪组织激素（AIM 2）。最后，我们会的评估产前护理模型对妊娠健康和怀孕期间脂质扰动的影响，将出生中心队列与在医院环境中接受产前护理的黑人妇女进行比较（AIM 3）。出生中心队列的招募将针对150名开始产前护理的妇女的保留。孕期计划的问卷和血液收集。劳动完成后，详细图表 - 将进行审查以确定案例和比较劳动功能障碍比较。为我们的决赛分析检查产前护理模型对脂质和人工成果的影响，我们将利用来自现有的167名黑人妇女的研究表和脂肪组学数据，具有相似的围产期水平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组之间的脂质特征和妊娠暴露。拟议的研究研究汇集了尖端技术和具有科学专业知识的多学科团队功能障碍，身体成分测量，全面的营养和体育活动分析，脂肪组学，种族差异调查和系统生物学方法与劳动功能障碍的面对影响孕产妇发病率和死亡率的最有影响力的条件。从这项研究获得的结果将提供功能信息，以确定预测劳动功能障碍的生物标志物可能性，改变未来的早期检测，有针对性的干预和预防劳动功能障碍。