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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持续上升，几乎超过所有其他发达国家。超过一半经历妊娠相关死亡的女性在死亡前没有可识别的危险因素劳动。对于这些女性来说，导致死亡或发病的一连串事件往往始于分娩功能障碍。目前关于分娩功能障碍的生理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下降的原因。脂毒性是一个系统范围的当过量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，并且社会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。我们推测血脂谱的变化可能提供了连接黑人女性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妊娠过程中产程功能障碍之前的脂质变化是如何发展的在独立生育中心接受产前护理的黑人妇女队列（目标 1），并衡量这些脂质变化受到怀孕健康的影响，包括母亲的行为、身体成分、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扰动的影响，将生育中心队列与在医院环境中接受产前护理的黑人妇女队列进行比较（目标 3）。生育中心队列的招募目标是保留 150 名首先开始产前护理的妇女三个月计划问卷调查和血液采集。分娩完成后，详细图表- 将进行审查以确定病例并进行分娩功能障碍比较。为了我们的决赛分析检查产前护理模式对血脂和分娩结果的影响，我们将利用来自现有 167 名围产期水平相似的黑人女性的调查问卷和脂质组学数据在附近医院诊所接受产前护理的生育中心人群面临的风险。差异分析将然后用于比较各组之间的脂质特征和妊娠暴露。拟议的研究研究汇集了尖端技术和具有劳动科学专业知识的多学科团队功能障碍、身体成分测量、综合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劳动力功能障碍——之一影响孕产妇发病率和死亡率的最有影响力的状况。从这项研究中获得的结果将提供功能信息，使预测产程功能障碍的生物标志物的识别成为现实的可能性，改变早期发现、有针对性的干预和预防劳动功能障碍的未来。