Evidence from human and animal studies show that chronic stress exposure and obesity synergize to elevate circulating stress and pro-inflammatory signals. What is less clear and particularly important for nursing mothers, however, is whether these signals translate to milk and affect infant development. Human milk contains many hormonal and immunological signals including cytokines, adipokines, immunoglobulins (Ig), and growth factors that mediate infant health and development; however, it is not known whether and to what extent maternal stress and obesity may alter these and produce adverse growth trajectories for infants. Because stressor exposure and diet are difficult to manipulate in postpartum women, social subordination in group-housed rhesus macaques represents a translational model to assess how maternal factors may affect milk immunobiology and negatively impact infant growth and health. To disentangle prepartum maternal stress from postpartum stress, fifty-six newborns will be cross-fostered to mothers of the same or different ranks. In addition, half of the mother-infant dyads will be maintained on a low calorie diet through lactation while the other half will be switched to a rich dietary condition. Behavioral assessments of maternal care, nursing patterns, and social rank will be obtained throughout lactation. Food intake in the mothers and infants during weaning will be monitored through automated feeders.
Aim 1 will test the hypothesis that chronic social stress and adiposity will synergize to increase stress and inflammatory signals in milk.
This aim will be accomplished by measuring cortisol, cytokine and adipokine markers in milk and serum from lactating rhesus monkeys of different social rank (dominant vs. subordinate) and postpartum diet exposure (high calorie vs. low calorie).
Aim 2 tests the hypothesis that chronic social stress and adiposity will interact to decrease immune defense components in milk. Milk levels of sIgA in lactating dams will be evaluated in parallel with stress and inflammatory markers studied in Aim 1. Finally, Aim 3 will determine the contribution of milk signals studied in aims 1 and 2 to infant growth and health trajectories. Specifically, it will test the hypothesis that pro-inflammatory cytokines and adipokines significantly predict infant growth in addition to milk energy in a rich dietary environment. Taken together, findings from this study will better define how milk signals induced by maternal stress and obesity may affect infant growth and health, consistent with the mission of NICHD. Furthermore, findings from this study will lead to prospective studies to determine what interventions alleviate these adverse effects of maternal stress and obesity on infant health.
Findings from this study will show how stress and obesity influence the immune and hormonal constituents of mother's own milk and subsequent infant growth. In addition, for mothers who are unable to breastfeed, a greater understanding of milk's bioactive factors may help improve the development of human milk substitutes in relation to infant health.
