2013 Annual Report
1a.Objectives (from AD-416):
The long-term objectives of this project are to determine the influence of dietary factors on growth, physiological, psychological and cognitive development and functioning in children. These objectives are being addressed in longitudinal studies documenting the effects of differences in early diet (breast feeding or infant formula) on these measures in preterm and term babies from infancy through childhood, and in cross-sectional studies in school-aged children assessing: a) the effectiveness of USDA School Breakfast and Lunch programs in maximizing neurophysiological and behavioral functions essential for learning, with the goal of understanding the relationship between diet and processes optimizing attention and learning while in school; and b) determining neurocognitive correlates and consequences of being overweight in children and how these factors may relate to the development of childhood obesity. Over the next 5 years we will focus on the following objectives:
Objective 1. Using a longitudinal study, evaluate the effects of infant diet (breast-milk, dairy- and soy-based formulas, and monosaccharide supplemented formula) on physiological, behavioral and cognitive development in infants and children.
Sub-Objective 1.A. Determine the growth and development of infants fed one of the three major infant diets (breast-milk, milk- or soy- based formula).
Sub-Objective 1.B. Determine the effects of monosaccharide-supplemented formula on the growth and development of healthy preterm and term infants.
Sub-Objective 1.C. Determine if early infant diet is predictive of later cognitive development and information processing abilities.
Objective 2. Determine the effects of diet composition, meal patterns and meal frequency on brain function and behavioral dynamics that are important for learning and school performance in well-characterized normal and overweight school children.
Sub-Objective 2.A. Determine the effects of variations in morning nutrition (skipping or eating different meals followed by a snack) on processes important for learning in normal weight and overweight children.
Sub-Objective 2.B. Determine the effects of lunch nutrition (skipping or eating different meals followed by a snack) on learning processes in normal weight and overweight children.
Objective 3. Characterize neurocognitive function that contributes to or is a consequence of obesity in children, including brain-function correlates of food-seeking behavior.
1b.Approach (from AD-416):
Children (infants, toddlers, and school-aged youths) will be studied longitudinally to evaluate the effects of infant diet (such as, breast-milk, dairy- and soy-based formulas, and other formulas) on physiological, behavioral and cognitive development in infants and children. Nutritional status assessments, anthropometric measurements, urine and blood analysis, and measures of psychological, neuropsychological, and cognitive measures will be obtained and analyzed. The effects of diet composition, meal patterns, and meal frequency on brain function and behavioral dynamics that are important for learning and school performance in normal and overweight school children will be assessed using validated survey instruments and state-of-the-art research equipment. Neurocognitive function will be characterized that contributes to or is a consequence of obesity in children, including brain-function correlates of food-seeking behavior.
During FY13, research has focused primarily on the ongoing longitudinal Beginnings study. This study is following the brain development, and behavioral development from birth through 6 years of age of 600 children who were fed one of the three major infant diets used in the United States (breast milk, milk-based and soy-based formula) and is the world's largest prospective, longitudinal study of its kind. Our target-population enrollment goal of 200/group was reached in FY12, and during this year we completed data collection for participants through age 2 years. Assessments were made on 187 participants during 206 visits this year. These included 28 children who had their 6-year visits, bringing the total number of children who have completed the full study protocol to 207. While this represents substantial progress, with three diets and data from both boys and girls, the study is far from complete. There are, however, complete data sets through age 2 years, and we have been analyzing these and writing manuscripts. We have studied various aspects of brain function (e.g., general mental development, language development and skills) and are relating these measures of brain development (e.g., cortical neural networks, and autonomic nervous system activity). Processing and updating age/diet group and measure-specific datasets are ongoing, labor-intensive processes. Data from these studies are providing answers to questions regarding how and the extent to which early nutritional status and diet influence growth, brain maturation, and mental development during the formative period from birth through early childhood. The Beginnings study is providing a substantial amount of data on brain development and function in healthy children, and documenting the influence of different infant diets on these measures. In view of international concerns about the safety and efficacy of soy formula, the documentation of this development in infants fed this plant-based formula is of particular importance. Our studies are providing an extensive dataset which includes measures of large numbers of physiological and neurobehavioral endpoints that have been needed to address these concerns. To date our results have shown that brain development, brain function, and other measures of physiological development are within normal ranges for all three infant diet groups. We are, however, detecting diet-related differences within the normal range that may have implications for future development. Importantly, the results to date involving substantial numbers of children have not revealed any adverse effects of soy formula on study measures. A component of the Beginnings study addresses the question of whether variations in infant diet can be related to differences in brain structure and mental capacity later in development. In these cross-sectional studies brain activity during language processing is being measured using high density recordings of brain electrical activity and functional magnetic resonance imaging (fMRI) in 8-year-old children who were fed either breast milk, milk formula, or soy formula as infants. The emphasis on language processing was based on early findings in the Beginnings study indicating subtle diet-related differences in processing speech sounds. This is the first study to use these technologies together to study the effects of infant diet on brain function in older children. The combination of electrophysiological and fMRI methods allows us to more precisely identify regions within the brain that are activated during language processing and therefore to more clearly understand how diet-related effects on brain function are mediated. In addition, MRI technology allows us to determine whether there are infant-diet-associated differences in brain structure, e.g., variations in the amount of white matter, evident in preadolescents. During this year total enrollment in this study was brought to 69. Of these, 59 have successfully completed the study protocol. We expect to complete enrollment of the planned target population of 20/infant-diet-type this year. We have been processing both imaging and electrophysiological data as they are collected, and will statistically analyze these data for group differences once the planned group populations have been reached. We have made significant progress in characterizing brain structure and neurocognitive function associated with body composition (lean vs. obese) in children, including brain-function correlates of food-seeking behavior. We have initiated a pilot study using fMRI procedures in which we are comparing brain function and behavior in normal weight (lean) and obese children in response to food images (which activate the food rewarding network) and under conditions requiring the child to demonstrate inhibition behavior (such as would be required to resist consuming unhealthy foods). In addition, we have used "Diffusion Tensor Imaging" to study brain "white matter", which is a covering of neuronal tracks or pathways used for communication of one brain region with another. We have also studied the regional brain "gray matter" to map the volume of specific brain areas and to assess total brain volume in these children. To date data have been successfully acquired on 10 normal weight and 8 obese children. Preliminary findings are suggesting that compared to lean children, obese children have a reduced ability to activate those brain regions necessary for inhibitory behavior required to make healthy food choices. The methodology being developed and standardized in these studies will form the basis for future studies on childhood obesity and brain function.
Heart rate development in breast-fed and formula-fed infants differs among boys but
not girls. Sex differences in the effects of dietary factors on physiology have been
documented in adults, but whether such effects are present during early development
has not been determined. Scientists at the Arkansas Children's Nutrition Center in
Little Rock, Arkansas, are studying the development of breast-fed and formula-fed infants (soy and milk formulas) and have found evidence of diet-related gender-specific influences on the development of a fundamental physiological parameter: heart rate. Based on measures of resting heart rate across the first two years of life, they observed that after 6 months, heart rate was faster in breast-fed than formula-fed boys, but similar in girls across diet groups. Since heart rate influences the delivery of blood-borne nutrients that fuel brain and body functions, the presence of diet- and gender-specific interactions on heart rate during early development has potential long-term implications for physiological and mental development. These findings further our understanding of the influence of early dietary factors on development, and similar results for formula-fed groups should help reduce concerns of parents and industry regarding the safety of soy formula.
Brain processes promoting discrimination of speech sounds are more developed in soy
formula-fed than milk formula-fed infants at 4 months. The majority of infants are
formula-fed by 6 months of age, but little is known about how different infant
formulas influence the early postnatal development of brain processes that are
important for language recognition. To address this question, scientists at the
Arkansas Children's Nutrition Center in Little Rock, Arkansas, compared brain responses to two syllables "ba" and "pa" (one presented more often than the other) in 4-month-old infants fed either milk formula or soy formula. Researchers found that brain processes that increase the ability to distinguish between these two speech sounds were less developed in infants fed milk formula. These results provide new information regarding early diet-related influences on the development of brain
processes fundamental to learning and neural plasticity, and should help reduce
concerns of parents and industry regarding the use of soy formula.
Early development of heart rate regulation differs between breast-fed and formula-fed infants. Heart rate control is critical to health, behavioral and cognitive function, yet it is not known if differences in infant diet are associated with differences in the development of heart rate control. In their longitudinal investigation (Beginnings study) of the development of breast-fed, soy formula-fed, and milk formula-fed infants, scientists at the Arkansas Children's Nutrition Center in Little Rock, Arkansas, are providing the first information regarding this question. Findings in 465 infants based on measures of resting heart rate across the first two years of life revealed that vagal tone--a parameter of the autonomic nervous system that regulates cardiac function by slowing heart rate--was within the normal range across groups but was lower after 6 months in breast-fed than formula-fed infants. Variations in vagal tone have been related to mental development and emotional behavior in infants, children, and adults. These findings provide new information regarding the influence of early infant diet on neurodevelopment and suggest that variations in early diet may contribute to the development of individual differences in autonomic heart rate control which is important in the regulation of attention, emotion, mental abilities and behavior. Further, these results should help reduce concerns of parents and industry regarding the use of soy formula.