PROJECT SUMMARY Optimizing early cognitive development is critical, as children with impaired cognition are at greater risk for neuropsychiatric disorders later in life. While it is known that breastfeeding promotes better cognitive development, few studies have identified specific components of breast milk that are involved in this process. One component that may be relevant is a group of non-digestible complex carbohydrates known as human milk oligosaccharides (HMOs). Animal studies reveal that certain HMOs enhance cognitive outcomes of memory, attention, and impulse control, and the relationship may be driven by several mechanisms. First, some HMOs are a source of sialic acid important for brain development. Second, HMOs are a source of prebiotics important for gut microbe development, which is likely to play a role in cognitive development and a focus of the parent R01. Although the first year of life is a critical window for brain development, it is unknown whether HMOs affect structural-functional organization of infant cognition. In this application, Dr. Paige Berger’s goal is to determine associations between HMOs and magnetic resonance imaging (MRI) measures of infant brain development (brain white matter myelination, cortical maturation). During the K99 phase, she will build on an existing NIH sponsored study (R01DK110793) by Dr. Michael Goran. In the parent R01, Hispanic mothers and normal birth weight infants are being followed, with frequent assessment of HMOs up to 24 months. In the proposed project, Dr. Berger will leverage the data and resources on HMOs in a subset of exclusively breastfeeding mother-infant pairs (n=65) at 1 and 6 months. Since brain white matter myelination and cortical maturation were not measured in the parent R01, Dr. Berger will collect these in infants at 1 and 6 months. The K99 hypothesis is that in normal birth weight infants (≥2500 g), brain white matter myelination and cortical maturation will be positively associated with HMOs. Dr. Berger will focus her K99 training on the development of expertise in structural-functional organization of infant cognition, and hone her skills in conducting clinical nutrition research in mother-infant pairs. She will learn the skills and techniques needed to complete the proposed research under her expert team (Drs. Goran, Bradley Peterson, Lars Bode, Leann Birch, Douglas Vanderbilt). Collectively, her expert team has a strong track record of training postdoctoral scholars transitioning to independence. In the R00 phase, Dr. Berger will apply the skills acquired during the mentored phase to initiate a new line of work in low birth weight infants (<2500 g), examining associations between HMOs and cognitive development. The proposed work will provide Dr. Berger with data and support to develop efficient and effective clinical trials, with future implications to validate the roles of HMOs that may have positive effects on cognitive development in a high-risk infant population.

PROJECT NARRATIVE Completion of the proposed study is an important first step in understanding how specific human milk oligosaccharides (HMOs) that are unique to mother’s milk, shape early brain and cognitive development in normal birth weight and low birth weight infants, at elevated risk for cognitive deficits. Results will provide data and support to develop efficient and effective clinical trials, with future implications to validate the roles of HMOs that may have positive effects on early brain and cognitive development.