Circadian Rhythms in Human Milk Cortisol: An Examination of Maternal and Environmental Regulators

母乳皮质醇的昼夜节律：母体和环境调节剂的检查

• 批准号: 10653545
• 负责人: Jennifer Hahn
• 金额: $ 46.15万
• 依托单位: UNIVERSITY OF CALIFORNIA, MERCED
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-04 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10653545
• 关键词: Animals; Award; Biological Markers; Brain; Breast Feeding; Breastfed infant; California; Circadian Rhythms; Circulation; Dairying; Development; Digestion; Electronics; Environmental Risk Factor; Exclusive Breastfeeding; Exhibits; Exposure to; Feeding Patterns; First Generation College Students; Funding; Genetic; Goals; Growth; Health; Height; Hispanic; Home; Hormonal; Hormones; Hour; Human; Human Milk; Hydrocortisone; Immunologics; Infant; Infant Development; Infant Health; Interdisciplinary Study; Intervention; Life Style; Light; Measures; Mental Depression; Metabolism; Milk; Mission; Modeling; Modernization; Mothers; National Institute of Child Health and Human Development; Neurocognitive Deficit; Non obese; Nutritional; Obesity; Outcome; Pattern; Periodicity; Peripheral; Persons; Play; Research; Research Personnel; Research Priority; Research Training; Rodent; Role; Sampling; Sleep; Sleep Disorders; Sleep Wake Cycle; Sleep disturbances; Stress; System; Systems Biology; Testing; Tissues; Training; United States National Institutes of Health; Universities; Variant; Weight; acute stress; circadian; circadian biology; circadian pacemaker; depressive symptoms; diaries; experience; high risk; improved; lifestyle factors; mammary; milk production; next generation; novel; persistent symptom; primary outcome; recruit; respiratory; sleep pattern; stress symptom; suprachiasmatic nucleus; undergraduate student; underserved students; virtual

PROJECT SUMMARY The development of healthy circadian biology is vital to infant health—infants with dysregulated circadian biology are at higher risk of sleep disorders, digestive issues, and neurocognitive deficits. One recently identified factor thought to entrain infant circadian biology is human milk, which changes dramatically over the day in terms of its nutritional, immunological, and hormonal composition. For example, cortisol levels in human milk are three times higher in milk produced in the morning compared to milk produced in the evening, although there is substantial between-person and within-person variation which is not well understood. Moreover, disruption to circadian biology is common in breastfeeding mothers due to artificial light exposure, obesity, and other modern lifestyle factors that could be undermining natural circadian variation in human milk. We seek to test a foundational model of the maternal and environmental factors that may disrupt natural circadian rhythms in milk cortisol, with the long-term goal of identifying targets of intervention to improve infant health. Milk cortisol was chosen as our primary outcome in this first study given that cortisol is an important puerperal regulator of genetic clocks in tissues throughout the body and a widely used biomarker of circadian health generally, and milk cortisol readily passes into infant circulation and has programming effects on the developing infant. We hypothesize that well- established direct (i.e. light) and indirect (i.e. obesity, sleep, stress and depression) regulators of circadian biology generally will also regulate circadian changes in human milk composition. With the help of undergraduate students supported by this R15 AREA award, we propose to recruit a sample of 105 exclusively breastfeeding mothers and measure environmental and maternal factors that may regulate circadian variation in milk cortisol. Over 1 week, mothers will be asked to provide 24-hour milk samples and to wear the Actiwatch Spectrum Plus to track ambient light exposure and sleep patterns. In addition, baseline assessments will be used to capture mothers' height and weight, chronic stress, and depressive symptoms; electronic daily diaries will measure mothers' acute stress and to capture daily infant feeding and sleep patterns. A multilevel growth-curve modeling approach will be used to examine within-person (Aim 1) and between-person (Aim 2) predictors of circadian variation in milk cortisol. We predict that on days when mothers experience higher (compared to lower) levels of circadian-incongruous light, sleep disturbance, and/or acute stress exposure, they will exhibit relatively blunted circadian rhythms in milk cortisol, characterized by relatively low morning milk cortisol and high evening milk cortisol. Moreover, we predict that mothers with higher rates of obesity, chronic stress, and/or depressive symptoms will have blunted circadian rhythms in their milk cortisol when compared to non-obese, non-chronically stressed, or non-depressed mothers. The results of study promise to significantly advance our understanding of the drivers of circadian biology in human milk, and may help identify novel targets for interventions that enhance infant circadian biology by bolstering circadian rhythms in human milk.

项目摘要 健康昼夜节律生物学的发展对于婴儿健康至关重要 - 昼夜节律生物学失调 最近确定的因素 人们认为婴儿昼夜节律生物学是人类牛奶，它在一天中发生了巨大变化 营养，免疫学和荷尔蒙组成。例如，人乳中的皮质醇水平为三倍 与晚上生产的牛奶相比，早晨生产的牛奶中的牛奶更高，尽管有大量 人际关系和人际关系变化尚不清楚。而且，昼夜节律的破坏 生物学在母乳喂养中很常见，因为人造光暴露，肥胖和其他现代生活方式很常见 可能会破坏人类牛奶中自然昼夜节律变化的因素。我们试图测试基础模型 在牛奶皮质醇中可能破坏自然昼夜节律的母体和环境因素中 确定干预目标以改善婴儿健康的长期目标。牛奶皮质醇被选为我们的 鉴于皮质醇是重要的遗传调节剂，这是第一项研究的主要结果 整个身体的组织，通常是昼夜循环健康的广泛使用的生物标志物，牛奶皮质醇很容易 进入婴儿循环，并对发育中的婴儿产生编程影响。我们假设这是一个很好的 建立的直接（即光）和间接（即肥胖，睡眠，压力和抑郁症）的调节器 生物学通常还将调节人奶成分的昼夜节律变化。在大学的帮助下 该R15地区奖的学生支持，我们建议招募105个独家母乳喂养样本 母亲并测量可能调节牛奶皮质醇变异的环境和母体因素。 在1周以上，将要求母亲提供24小时的牛奶样品并佩戴Actiwatch Spectrum Plus 跟踪环境光曝光和睡眠方式。此外，将使用基线评估来捕获 母亲的身高和体重，慢性压力和抑郁症状；电子每日日记将测量 母亲的急性压力并捕获每天的婴儿喂养和睡眠方式。多层增长曲线建模 方法将用于检查人际关系（AIM 1）和人际关系（AIM 2）昼夜节律的预测指标 牛奶皮质醇的变化。我们预测，在母亲经历更高（与较低）水平的天数 昼夜节律的光，睡眠障碍和/或急性压力暴露，他们会暴露于相对钝的 牛奶皮质醇中的昼夜节律，其特征是早晨牛奶皮质醇和高牛奶 皮质醇。此外，我们预测，肥胖，慢性压力和/或抑郁率较高的母亲 与非肥胖相比，症状会在其牛奶皮质醇中钝化昼夜节律 压力或不沮丧的母亲。研究结果有望大大提高我们对 昼夜节律生物学的驱动因素，可能有助于确定增强干预措施的新目标 婴儿昼夜节律生物学通过增强人类牛奶中的昼夜节律。