2005 Annual Report 1.What major problem or issue is being resolved and how are you resolving it (summarize project aims and objectives)? How serious is the problem? What does it matter? The brain develops with a time course of events that is influenced by many factors, including nutritional status and dietary factors. The primary goal of this research is to determine the effects of diet and nutritional status on brain development and function in children. We are particularly interested in learning how to best "feed the brain" to maximize development and cognitive function in children. Studies currently focus upon:. 1)the effects of breast feeding and formula feeding of normal infants born after a full-length pregnancy (term infants);. 2)development of new diets that promote brain development and function in normal babies born prior to full term (pre-term); and. 3)learning about the effects of nutritional status and diet intake of school children on brain function, especially as it relates to learning, memory, attention, and intelligence (generically referred to as cognition). Our research uses standardized state-of-the-art methodology and equipment to assess dietary intake and nutritional status of children. Research collaborators include nutritionists and child psychologists/ neuroscientists who work as a team to address important questions related to the influence of nutritional status and dietary intake on brain function. Our studies involve obtaining responses to a battery of physiological and behavioral tests. The tests are designed to assess specific brain functions that are predictive of future central nervous system function in such important areas as language acquisition, math skills, learning, memory, attention, and intelligence. Additionally, these tests are designed to account for factors such as age and gender. Thus, there are several major problems being addressed by these studies. We are:. 1)determining the effects of diet and nutrition on brain development and brain function; and. 2)learning about the effects of complete diets, specific nutrients, and other dietary factors on brain function. Equipped with this knowledge, it will eventually be possible to design diets that work to optimize normal brain development and maximize cognitive potential. The questions being addressed in this program are very important and consistent with the National Program - 107 goals. This research directly supports ARS Strategic Plan Goal #4, Improve the Nation's Nutrition and Health. There are very few researchers in this area and virtually no studies being conducted to address many important questions related to nutrition/dietary intake and human brain development/function. There are more than 350,000 infants born in the low birth-weight range in the US each year. These are essentially normal infants, but because they were born prematurely, their brain growth and development are hindered relative to infants born after a full-term pregnancy. Normally, brain development would be fueled by nutrients and specific factors that cross through the placenta from the mother to the fetus, and many of these same factors are also present in milk produced by mothers who have normal full-length pregnancies. The identity and actions of these factors are only partially understood, and most of our knowledge has come from studies of breast milk. Currently marketed infant formulas do not contain most of these factors, either because of expense or because their functions have not been documented sufficiently. Even though there are special formulas made just for pre-term infants, they lack many of the factors thought to be important for normal brain development. Thus, many of these children grow up to have central nervous system defects that result in hyperactivity or disorders of cognition and attention. This not only impacts the quality of life for these children and their families, but has a significant negative societal impact in terms of lost work potential, increased stress on school systems, and increased public expenses. Thus, this is a serious problem that carries with it life-long consequences. Two studies at the Arkansas Children's Nutrition Center focus on the development of new diets that will promote brain development and function, while other studies address similar important questions related to optimizing brain development and function through diet and nutrition. 2.List the milestones (indicators of progress) from your Project Plan. This research includes three ongoing projects studying the effects of diet and nutrition on psychological and biological functioning in infants and children. Two are longitudinal studies in which participants are assessed multiple times between: A) birth and age 6 years (Soy Project); and B) birth and age 3 years (Formula Supplement Project). In both projects, growth, body composition, neurophysiology and cognitive/psychological development of infants will be studied. The third project studies and evaluates the effects of the USDA school breakfast and lunch diets on neurophysiologic and cognitive functions important for learning in school-aged children. The milestones for each project are provided below. Project 1: Soy-Based Formula Studies. Researchers are studying growth, body composition, organ growth, neurophysiology and cognitive development of infants receiving breast milk, milk-based formula, or soy-based formula over their first six years of life (it will take 8-10 years total to complete this investigation). It will provide the first, systematic comparative evaluation of the acute and longer term effects of these basic diets on these fundamental physical, physiological, and cognitive aspects of infant and child health and development. Year 1 (FY 2004): Office of Scientific Quality Research (OSQR) peer review of the project, consisting of this research project, is completed and certified. Year 2 (FY 2005): Recruitment for this study will be ~30% complete. We anticipate 3-4 abstracts and/or brief reports based on preliminary diet-related findings in 3-month-old infants will be submitted. Year 3 (FY 2006): The total number of subjects has been increased by 300 because our initial results indicate that infants fall into several different categories within each diet group and a large number is needed to detect statistical differences. Recruitment for this study (total n=600) will and we have roughly 75/diet group now or roughly 30% enrolled. We expect to enroll another 90 for the next year (approximately 50% enrolled). We anticipate 3-4 abstracts and/or brief reports based on preliminary diet-related findings in 3-month-old infants will be submitted. These initial reports will deal with brain electrical activity measures (event-related potentials) of:. 1)auditory;. 2)startle responses;. 3)language development;. 4)social interactions; and/or. 5)comparative brain development. Preliminary findings in 6-month-old infants will also be submitted. These reports will include comparisons with 3-month data to track diet-related developmental differences in brain electrical activity measures (event-related potentials) of language development and brain electrical activity assessed during resting periods. Year 4 (FY 2007): We expect to enroll another 90 subjects (increasing to n = 405, or 68% of total). We anticipate 3-4 abstracts and/or brief reports based in 3- and 6-month-old infants, related to auditory startle responses and social interactions. Preliminary findings in 9- and 12-month-old infants will also be submitted. These reports will include comparisons with earlier visits to track diet-related developmental differences in brain electrical activity measures of language development and brain electrical activity assessed during resting periods. Initial analyses of metabolic data (plasma and urine levels of soy phytochemicals and their metabolites) collected in 3- and 6-month-old infants will be conducted and preliminary findings reported. Year 5 (FY 2008): We expect to enroll another 95 subjects (increasing to n = 500, or 83% of total). Data from the 3-month-old infants will be completed and written up for publication. We anticipate 3-4 abstracts and/or brief reports based on additional diet-related findings in 6-, 9-, and 12-month-old infants on measures listed above. Up-dating analyses and reports of metabolic data (plasma and urine levels of soy phytochemicals and their metabolites) collected in 3- and 6-month-old infants. Project 2: Low Birth Weight Formula Supplement Study. This project involves enhancing the composition of infant formula through the addition of specific sugars (monosaccharides) normally available to developing infants through the placenta or via breast milk. The aim is to improve brain development and function in premature low birth weight infants by providing nutritional benefits not currently available in formula. Year 1 (FY 2004): Office of Scientific Quality Research (OSQR) peer review of the project, consisting of this research project, is completed and certified. Year 2 (FY 2005): By the end of 2005, all breast milk and blood samples will have been collected, processed, and the supplement formulated, manufactured, and tested. The milk composition will be published. Begin recruitment and study (growth, health, cognitive and physiological measures) of term and low birth weight infants. Year 3 (FY 2006): Based upon new information, this project will:. 1)determine the oligosaccharides in placental and cord blood;. 2)conduct initial studies in infant pigs; and. 3)conduct safety trials in adults. Thus, these three new studies have already been approved by the IRB or are in review currently. We plan to conduct these studies and in the order listed above. We will use the information from these studies to formulate the diet, get it manufactured and begin the study. We also plan to publish the results of the breast milk analyses and perhaps we will have enough data on the placental study to submit an abstract on those data. We will begin recruitment and study (growth, health, cognitive and physiological measures) of term and low birth weight infants. Year 4 (FY 2007): We expected to recruit about one-third (n=90) of the projected study population. Abstracts and brief reports based on updated initial and 6-month-old infants will be submitted. These will continue to track diet-related developmental differences in brain electrical activity measures of language development and brain electrical activity assessed during resting periods, and will include evaluations of data related to auditory startle responses and social interactions. Year 5 (FY 2008): It is expected that recruitment should be about two-thirds complete by the end of the year. Preliminary findings in 12-month-old infants will be submitted. These reports will include comparisons with neonatal and 6-month data to track diet-related developmental differences in brain electrical activity measures of language development and brain electrical activity assessed during resting periods. Data from the initial neonatal assessments will be submitted for publication. We anticipate 3-4 abstracts and brief reports based on updated findings in 6- and 12-month-old infants on measures listed above. These reports will include comparisons across study visits to track diet-related developmental differences study measures, e.g., brain electrical activity measures of language development and brain electrical activity assessed during resting periods. Preliminary findings in 2-year-old babies will also be analyzed and submitted for presentation and publication. These reports will include comparisons across visits to track diet-related developmental differences in brain electrical activity measures of language development, brain electrical activity assessed during resting periods, and other behavioral and physiological measures. Project 3: School Breakfast-Lunch Studies. This series of studies is designed to evaluate the effects of the USDA school breakfast and lunch diets on neurophysiologic and cognitive functions important for learning in school-aged children and provide data to help improve the influence of these food assistance programs on processes important in learning. Year 1 (FY 2004): Office of Scientific Quality Research (OSQR) peer review of the project, consisting of this research project, is completed and certified. Year 2 (FY 2005): Recruitment and data analysis for this study will be completed and the initial full-study papers summarizing the results from ~100 children will be submitted for publication. The protocol for the next study in this series will be submitted for IRB approval and piloting conducted and recruitment (n=185, ~6/month; 20% attrition rate) and data acquisition initiated. Year 3 (FY 2006): Recruitment and testing of all subjects in the initial school breakfast study has been completed and the data will be processed. We anticipate 2-3 articles on measures relating autonomic (e.g., heart rate, respiration) and brain electrical activity (EEG), attention, memory, and performance. The protocol for the next study in this series will be submitted for IRB approval, and piloting of the protocol conducted, and recruitment (n=185, ~ 6/month; 20% attrition rate) and data acquisition initiated. Year 4 (FY 2007): It is expected that subject recruitment for this study will be completed. Data will be processed and 2-3 abstracts and brief reports will be submitted. Year 5 (FY 2008): 2-3 full-study papers summarizing the results from ~ 150 children will be submitted. Development of the protocol for the next study in this series will be submitted for IRB approval. 4a.What was the single most significant accomplishment this past year? SKIPPING BREAKFAST TENDS TO SLOW HEART RATE AND REDUCES ATTENTION Identifying the disparity between children not eating breakfast versus those consuming breakfast is necessary to understand the full benefits of a healthy start to the day. Scientists at the Arkansas Children's Nutrition Center, at Little Rock, AR, have demonstrated that children who skip breakfast have a lower heart rate than when they eat breakfast. Extended morning fasting counteracts the natural circadian rhythm in which heart rate increases in the morning hours. Children who eat breakfast also show faster reaction times and changes in EEG activity associated with increased attention. Thus, not consuming breakfast tends to slow heart rate and reduce attention which further reemphasizes the importance of a healthy breakfast to start the day. 4b.List other significant accomplishments, if any. INFANTS FED SOY FORMULA HAVE BRAIN ACTIVITY SIMILAR TO MILK-FORMULA FED INFANTS Additional information is needed that evaluates the brain activity of infants fed soy based formula versus infants fed other formulas. Scientists at the Arkansas Children's Nutrition Research Center, Little Rock, AR, have determined through preliminary data that infants fed soy formula have basal brain activity similar to that of breast-fed infants or infants fed milk-based formula. This is important and reduces concerns about high levels of phytoestrogens in soy-fed infants. Such findings may have an impact on the acceptance of soy-fed formulas worldwide. 4c.List any significant activities that support special target populations. None. 5.Describe the major accomplishments over the life of the project, including their predicted or actual impact. "Failure-to-Thrive" is a condition in which children do not grow properly, even though they have adequate nutrition. The Arkansas Children's Nutrition Center has studied these children and found that they utilize energy less efficiently than children who grow normally. The Arkansas Children's Nutrition Center has also established the world's largest and most complete study on the effects infant feeding has on brain development and function. Thus far, researchers have observed that infants fed milk-based diets differ from breast-fed and soy-fed infants in some brain functions, while in other brain functions, soy-fed infants differ from breast-fed and milk-fed infants. It appears from our preliminary findings that brain development and function associated with all three "diets" results in the same end results; however, the infants reach them in different ways. The questions being addressed in this program are very important and consistent with the National Program - 107 goals. This research directly supports ARS Strategic Plan Goal #4, Improve the Nation's Nutrition and Health. 6.What science and/or technologies have been transferred and to whom? When is the science and/or technology likely to become available to the end-user (industry, farmer, other scientists)? What are the constraints, if known, to the adoption and durability of the technology products? None. 7.List your most important publications in the popular press and presentations to organizations and articles written about your work. (NOTE: List your peer reviewed publications below). National and International Meetings and Presentations: The ACNC research team has presented more than 12 presentations at national and international meetings, including two presentations that were chosen from over 16,000 by the Public Information Committee to be included in a Press Book Submission that is distributed to national and international media services. Our group was chosen to be interviewed by several media outlets on their work. Local Presentations: The ACNC investigators and staff presented many local presentations at research groups at the University of Arkansas for medical Sciences, the Arkansas Children's Hospital and at several service organizations: Departments of Psychiatry, Pharmacology/Toxicology, etc. Workshops and Special Meetings: The Brain Development and Function Group of the ACNC organized and sponsored an international symposium entitled: Cortical Event Related Potentials and Early Language Development: Variations with Age, Gender and Nutrition. Scientist from four countries attended the two-day event. Review Publications Pivik, R.T., Dykman, R.A. 2004. Cardiovascular effects of morning nutrition in preadolescents. Physiology and Behavior. 82(2-3):295-302. Gilchrist, J.M., Wiggins, P.A., Brackenbury, J., Crook, T.A., Brodie, M., Stanley, L., Badger, T.M. 2004. Effects of diet on metabolism, body composition, and brain function in infants/children. Arkansas Chapter of the American Dietetic Association Annual Meeting. Paper No. 203. Crook, T.A., Wiggins, P.A., Gilchrist, J.M., Dykman, R.A. 2004. Body composition among children ages 8 to 15 who had inadequate growth in early childhood. Arkansas Chapter of the American Dietetic Association Annual Meeting. Paper No. 102. Pivik, R.T., Dykman, R.A. 2004. The effects of eating breakfast on the contingent negative variation response in preadolescents: gender correlates. Society of Psychophysiological Research. 41(S1). Paper No. 26. Pivik, R.T., Dykman, R.A. 2004. Contingent negative variation in preadolescents: gender correlates. Society of Psychophysiological Research. 41(S1). Paper No. 24. Pivik, R.T., Dykman, R.A. 2004. Endogenous blinks and the contingent negative variation: synergistic interactions. Society of Psychophysiological Research. 41(S1). Paper No. 25. Dykman, R.A., Pivik, R.T. 2004. The effects of eating breakfast on the contingent negative variation response in preadolescents. Program No. 202.18. Abstract Viever/Itinerary Planner. Washington, DC: Society for Neuroscience. Pivik, R.T., Jing, H., Gilchrist, J.M., Dykman, R.A. 2004. Thinking outside the breast: ERP comparisons of speech stimuli processing in 3-month-old breast and milk fed infants. Society of Psychophysiological Research. 41(S1). Paper No. 27. Jing, H., Pivik, R.T., Gilchrist, J.M., Dykman, R.A., Badger, T.M. 2004. Sex differences in processing speech stimuli in 3-month-old breast-fed infants: an ERP study. Program No. 665.4. Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience. Pivik, R.T., Dykman, R.A., Badger, T.M. 2005. Eating or skipping breakfast: effects on resting EEG activity and heart rate. The FASEB Journal. 19(4):A434. Jing, H., Dykman, R.A., Pivik, R.T., Gilchrist, J.M., Badger, T.M. 2005. Auditory event-related potentials in breast-fed, milk-fed, and soy-fed infants at 3 and 6 months of age. The FASEB Journal. 19(4):A1000. Carpenter, J.S., Gilchrist, J.M., Chen, K., Gautam, S., Freedman, R.R. 2004. Hot flashes, core body temperature, and metabolic parameters in breast cancer survivors. The Journal of the North American Menopause Society. 11(4):375-381. Jing, H., Dykman, R.A., Gilchrist, J.M., Pivik, R.T. 2005. Power spectral characteristics of resting eeg in breast-fed, milk-fed, and soy-fed infants at 3 months of age. Society for Neuroscience - Cognitive Neuroscience Meeting, April 10-12, 2005. Supplement 1, p. 56. Casey, P.H., Black, M., Cook, J., Goolsby, S., Frank, D., Berikowitz, C., Cutts, D., Zaldivar, N., Heeren, T., Levenson, S. 2004. Food insecurity is not associated with overweight status in 2 year old children. American Pediatric Society / The Society for Pediatric Research. 55(4):221A. Stuff, J.E., Casey, P.H., Szeto, K., Gossett, J., Weber, J., Simpson, P., Champagne, C., Connell, C., Harsha, D., Robbins, J., Mccabe-Sellers, B., Bogle, M.L. 2005. Household food insecurity and adult chronic disease in the lower Missisippi Delta. The FASEB Journal. 19(4):A986.