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.