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.

项目总结 健康昼夜节律生物学的发展对婴儿健康至关重要--昼夜节律失调的婴儿 睡眠障碍、消化问题和神经认知缺陷的风险更高。最近确定的一个因素 被认为携带婴儿昼夜节律生物学的是母乳，它在一天中发生了戏剧性的变化，就其 营养、免疫和荷尔蒙成分。例如，母乳中的皮质醇水平是 早晨生产的牛奶比晚上生产的牛奶含量更高，尽管有大量的 人与人之间和人内的差异，这一点还没有被很好地理解。此外，对昼夜节律的干扰 由于人工光照、肥胖和其他现代生活方式，母乳喂养的母亲普遍存在生物学问题 可能破坏母乳的自然昼夜节律变化的因素。我们试图测试一个基础模型 可能扰乱牛奶皮质醇自然昼夜节律的母体和环境因素，与 确定改善婴儿健康的干预目标的长期目标。牛奶皮质醇被选为我们的 这第一项研究的主要结果是皮质醇是产后基因时钟的重要调节器 全身的组织和广泛使用的生物标记物，通常是昼夜健康的标志，以及牛奶皮质醇 进入婴幼儿循环，对发育中的婴幼儿有规划作用。我们假设得很好- 建立直接(如光)和间接(如肥胖、睡眠、压力和抑郁)的昼夜节律调节器 生物学通常也会调节母乳成分的昼夜变化。在大学生的帮助下 在R15地区奖的支持下，我们建议招募105名纯母乳喂养的学生 并测量可能调节乳汁皮质醇昼夜变化的环境和母体因素。 在超过一周的时间里，母亲们将被要求提供24小时牛奶样本，并佩戴Actiwatch Spectrum Plus 以跟踪环境光线暴露和睡眠模式。此外，将使用基线评估来获取 母亲的身高和体重、慢性压力和抑郁症状；电子日记将测量 这项技术可用于监测母亲的急性压力，并记录婴儿的日常喂养和睡眠模式。一种多水平增长曲线模型 方法将用于检查人内(目标1)和人与人之间(目标2)对昼夜节律的预测 牛奶皮质醇的变化。我们预测，当母亲经历更高(与更低)水平的 昼夜节律不协调的光线，睡眠障碍，和/或急性应激暴露，他们将表现出相对迟钝 牛奶皮质醇的昼夜节律，其特征是早晨牛奶皮质醇相对较低，而晚上牛奶皮质醇相对较高 皮质醇。此外，我们预测，肥胖、慢性压力和/或抑郁发生率较高的母亲 与非肥胖者相比，非慢性肥胖者的乳汁皮质醇中的昼夜节律减弱。 有压力的，或没有抑郁的母亲。研究结果有望极大地促进我们对 母乳中昼夜节律生物学的驱动因素，并可能有助于确定新的干预目标，以增强 通过支持母乳中的昼夜节律来实现婴儿的昼夜节律。