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