Human Milk as a Pathway for Intergenerational Transmission: The Impact of Maternal Anxiety on Milk Immune Components and Infant Uncinate Fasciculus Microstructure

Abstract

Infancy is a unique time characterized by a profound link between mothers and infants. Infants rely on their mothers for all aspects of their survival, making mothers arguably the most salient influence in their lives. This close relationship provides infants with a range of beneficial resources for growth and development; however, when mothers lack access to resources to cope with stressors themselves, this can lead to adverse outcomes for infants. Traits such as anxiety, could either act as a resource for mothers (e.g., low trait anxiety) or a stressor (e.g., high trait anxiety). High trait anxiety may result in chronic activation of the stress response system due to evaluation of neutral stimuli as a threat. One result of chronic activation of stress is the dysregulation of the immune system, likely contributing to the long-term health outcomes we observe. Notably, human milk contains immune mediators such as Interleukin-6 and C-reactive protein, potentially exposing infants to maternal immune system function and, indirectly, to maternal stress. Though there is strong evidence that human milk supports healthy infant brain development, there is a paucity of information on the effects of increased exposure to immune system biomediators within milk, including which maternal factors may impact them. As immune biomediators influence developing white matter (WM) structure, specifically in areas that mediate our stress response, they may contribute to the development of adverse mental and physical health outcomes. Therefore, investigating tracts that connect regions involved in the stress response, such as the uncinate fasciculus (UF), may help characterize one pathway for the intergenerational transmission of stress. Utilizing maternal self-reports, milk samples, and infant diffusion tensor imaging during the first year postpartum from the UNC/UMN Baby Connectome Project, this dissertation sought to address two questions: 1) Does maternal trait anxiety impact concentrations of milk immune components, and 2) Do milk immune components impact infant UF fractional anisotropy (FA; an estimate of directional dependence of water reflecting myelin integrity) during the first-year post birth? Results from this study found no significant relationships between maternal trait anxiety and IL-6 presence (OR = 0.95, p = 0.15) but did find a significant positive relationship with CRP (B = 0.06, p = .048). The second, exploratory analysis found that presence of IL-6 was related to increased right UF FA (F(1,24) = 4.30, p = .050, η^2 = 0.16), but not left UF FA (F(1, 24) = 2.36, p = 0.138, η^2 = 0.10). These results provide evidence that maternal factors influence milk immune components and milk immune components influence infant neurodevelopment; however, more research is needed to definitively characterize these relationships.