2006 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? Why 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)learning about the effects of nutritional status and diet intake of children on brain function, especially as it relates to learning, memory, attention, and intelligence (generically referred to as cognition); and. 3)development of new diets that promote brain development and function in normal babies born prior to full term (pre-term). 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. These 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 by year the currently approved milestones (indicators of research progress) This research includes three ongoing projects studying the effects of diet and nutrition on psychological and biological functioning in infants and children. One is an ongoing prospective, observational longitudinal study in which participants are assessed multiple times between birth and puberty (Soy Project). A second project studies and evaluates the effects of the diet on neurophysiologic and cognitive functions important for learning in school-aged children. Thus far, focus has been on USDA school breakfast and lunch diets. A third project is still in the preliminary stages and it focuses on diets that will promote extra-uterine brain growth and development in children between birth and age 3 years (Formula Supplement Project). In projects 1 and 3, growth, body composition, neurophysiology and cognitive/psychological development of infants will be studied. 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: 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. Project 3: 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): This project will:. 1)conduct initial studies in infant pigs; and. 2)conduct safety trials in adults. These studies have already been approved by the IRB. 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. Abstracts and/or reports will be prepared and submitted. Year 5 (FY 2008): Assuming that the data from year 4 (2007) are positive and suggest that we can proceed, and assuming all the resource limitations have been resolved, it is expected that recruitment for the infant studies will begin and studies will be initiated. We anticipate an abstract based on updated findings in 6-month-old infants on developmental measures described in the protocol. 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. 4a.List the single most significant research accomplishment during FY 2006. New "Beginnings" for Soy Formula Research Some international countries and national scientific entities have questioned the safety of soy formula in infants. The Arkansas Children's Nutrition Center, Little Rock, AR "Beginnings study" is the largest longitudinal study undertaken to date to document the early and long term developmental effects of breast vs. formula (milk-based; soy-based) feeding using a battery of physiological, cognitive, behavioral, and growth measures in healthy infants. Our research was used at the 2006 National Institute of Health expert panel review to demonstrate that soy-fed infants do not differ in the brain function testing we have done to date. This is providing an unprecedented multidimensional accounting of the influence of early diet on growth, physiological, cognitive and behavioral development in a large sample of participants that are followed from infancy through childhood. (NP-107 Goal #4, Improve the Nation's Nutrition and Health) 4b.List other significant research accomplishment(s), if any. Increasing Mental Cognition with Breakfast A greater understanding of the full impact of school breakfast is needed to communicate the importance of a healthy start of the day for each student. The Arkansas Children's Nutrition Center, Little Rock, AR "School Breakfast study" is the most extensive investigation to date documenting the effects of a the USDA School Breakfast Program approved meal on neurophysiological and behavioral functions important in learning. As a result of the research, the study has identified physiological processes associated with improved information processing and performance following breakfast, and that significant short-term fasting-related decreases heart rate which may indicate greater cardiovascular reactivity to diet restrictions in children. Such results demonstrate the need for school youth to partake in this meal at the beginning of the day. (NP-107 Goal #4, Improve the Nation's Nutrition and Health) 4c.List significant activities that support special target populations. None. 5.Describe the major accomplishments to date and 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 Arkansas Children's Nutrition Center has: a) identified physiological processes associated with improved information processing and performance following breakfast; and, b) shown significant short-term fasting-related decreases in heart rate that may index greater cardiovascular reactivity to diet restrictions in children. The prospective, longitudinal observational study of infants fed breast milk, milk-based formula or soy-based formula is providing an unprecedented multidimensional accounting of the influence of early diet on growth, physiological, cognitive and behavioral development in a large sample of participants that are followed from infancy through childhood. The questions being addressed in this program are 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). Newspapers/Magazines: ACNC scientists: gave radio interviews (KARN); had stories published in several newspapers (Arkansas Democrat/Gazette, Daily Health News, Washington Post, LA Times, Chicago Sun Times, Dallas Morning News); and articles in magazines (Parent, Cooking Light, Science World, Science News, Science Watch). Local Presentations: ACNC investigators and staff have given numerous talks and presentations in the local community, including: Physiology/Biophysics Pharmacology/Toxicology; to the ACH Clinical Staff; 5-A-Day Health Fair; Arkansas Cancer Research Center; Baptist Health Fair; Healthy Kids Summit; the ACH Health Fair; Life Quest; Arkansas Children's Hospital Research Institute; and the Annual Capital Research Expo. We have given more than 16 tours through the ACNC for various groups, including: ACH board and donors; dietetic interns; students; parents, organizations, candidates and perspective subjects, 4H. National and International Meetings and Presentations: The ACNC research team has presented more than 25 presentations at national and international meetings. Workshops and Special Meetings: ACNC was represented at the recent NIH Panel review of soy formula and genistein and was the organizer of the 6th International Conference on Soy Health held in Chicago where several ACNC investigators presented. ACNC Investigators gave several invited talks and participated in several invited workshops on such issues as health effects of soy, milk proteins, fruits and rice, as well as other nutritional issues to the North Little Rock School District, Arkansas Dietetic Association, American Council on Fitness and Nutrition, American Heart Association, and Small Fruits Research Group. Review Publications Jing, H., Pivik, R.T., Gilchrist, J.M., Badger, T.M. 2005. Effects of breast milk, milk formula and soy formula on global field power of event-related potentials to speech sounds at 6, 9, and 12 months of age [abstract]. Annual Meeting of Society for Neuroscience, Washington, D.C., November 12-16, 2005. Program No. 643.7. Jing, H., Pivik, R.T., Dykman, R.A. 2006. An approach to scaling event-related potentials for comparisons of topographic shapes using regression analysis. Journal of Neuroscience Methods. 151(2):239-249. Pivik, R.T. 2006. Effects of morning nutrition on phasic modulation of EEG alpha activity during an attentional task in preadolescents. Annual Meeting of the Society for Neuroscience, Washington, D.C., November 12-16, 2005. Program No. 876.10. Pivik, R.T., Dykman, R.A., Tennal, K., Gu, Y., Badger, T.M. 2006. Skipping breakfast: gender effects on resting heart rate measures in preadolescents [abstract]. The FASEB Journal. 20(4):A187. Pivik, R.T. 2005. Preliminary results of a longitudinal study of infants fed soy formula: brain development and function. In: Proceedings of the "Effects of Soy on Growth and Development: How Much Do We Know?", Chicago, Illinois. 2005 CDROM. Jing, H., Pivik, R.T., Gilchrist, J.M., Badger, T.M. 2006. EEG power spectral changes in breast fed, milk-formula fed or soy-formula fed infants in the first 6 months of life. The FASEB Journal. 20(4):A598. Li, J., Pivik, R.T., Jing, H., Gilchrist, J.M. 2006. Cortical event-related potentials to speech sounds in 3-month old breast and formula-fed infants. Online Methods in Children's Language Processing, March 21-22, 2006, CUNY Graduate Center, New York, New York. Available: http://qcpages.qc.cuny.edu/~efernand/childlang/posters.htm.