Research Highlights

In fiscal year 2012, ACHRI researchers received over $27 million in grants and contracts from federal, state, and private agencies, industry sponsors, and philanthropic donations. Over 120 researchers, many who are physicians at ACH, conduct research on the ACH campus. Researchers at ACHRI strive to move discoveries quickly from the laboratory bench to the bedside for the benefit of children receiving care at ACH and throughout the world.

ACNC Acquires State of the Art Instrument to Measure Body Composition in Children
Until now, there has been no single technology or instrument that allows investigators to determine the body composition (fat, muscle, bone and water) of children from birth through puberty.  The Arkansas Children’s Nutrition Center commissioned a unique Nuclear Magnetic Resonance (NMR) machine to be built to accommodate study of children from birth (~6 pounds) through 120 pounds.  Scientists at the ACNC validated the usefulness of the NMR instrument in pigs of the same size as the children they plan to study in future protocols.  This technology and instrument will allow researchers to study the same children in the same instrument in longitudinal studies from birth and greatly improve the precision and accuracy of our measurements.  

Asthma
The National Institutes of Health (NIH) has awarded investigators at the Arkansas Children’s Hospital Research Institute (ACHRI) a 5-year, $2.2 million grant to explore whether school-based telemedicine sessions with doctors can help students in rural areas control their asthma. As the most common chronic childhood disease, asthma disproportionally affects minority and low-income children and can be especially burdensome for those who live far away from asthma specialists.

The Reducing Asthma Disparities in Arkansas (RADAR) research team, led by ACHRI investigator Tamara Perry, MD, will examine 12 school districts in rural east Arkansas counties, placing video-conferencing systems in six so that recruited students with asthma can have regular education appointments with specialists in Little Rock. The remaining schools will act as control sites. Researchers believe that the students who participate in the school-based asthma education and monitoring will gain better control over their disease, with fewer episodes of acute breathing problems.

Autoimmune Disease
Immune responses typically protect the body from infectious diseases. When the immune response instead targets its own tissues, autoimmune diseases such as lupus, scleroderma, alopecia, and autoimmune hepatitis can occur. Various interacting factors are required for disease development. Dr. Kathleen Gilbert and her team at ACHRI’s Immunotoxicology Center are examining how exposure to common environmental toxicants unlocks autoimmune disease. Dr. Gilbert has studied immunotoxicity at ACHRI for a decade. In 2010, the National Institutes of Health awarded Dr. Gilbert a three-year grant of $997,000 to investigate how chronic low-level exposure to the common environmental pollutant trichloroethylene (TCE) affects immune cells and promotes autoimmunity.

Blueberry diet and atherosclerosis
Cardiovascular disease is a major killer in the United States.  Scientists at the Arkansas Children’s Nutrition Center in Little Rock, AR tested the hypothesis that feeding a diet rich in blueberries prevents the onset of atherosclerosis.  They found that the mean lesion area for mice fed a blueberry diet was significantly reduced compared to control diet mice.  Interestingly, decreases in lesions did not appear to be related to serum LDL-cholesterol and triglyceride levels. These findings may provide additional evidence for recommending increased consumption of fruits to prevent chronic inflammatory diseases.

Congenital Heart Defects
Research efforts of the Arkansas Center for Birth Defects Research and Prevention includes studies of possible epigenetic causes of Congenital Heart Defects (CHDs). Epigenetics research investigates changes in gene expression caused by mechanisms other than DNA sequence changes, and the Birth Defects Genomics Laboratory has conducted studies assessing maternal DNA methylation, an epigenetic event, and CHDs. They found that various maternal genes were differentially methylated in mothers with pregnancies affected by CHDs when compared to mothers with unaffected pregnancies. These findings provide initial evidence of a new avenue of research for CHDs and a potential target for therapeutic intervention.

Diet-mediated mechanisms of breast cancer protection
Increased maturation of mammary tissue is linked to lower breast cancer risk and soy protein containing diets are known to accelerate this process.  However, the mechanisms underlying these effects are unknown.  Scientists at the Arkansas Children’s Nutrition Center in Little Rock, AR were the first to show that the soy isoflavone, genistein, regulates “tumor suppressor proteins” (named; PTEN, E-cadherin, and p53) and are involved in the mechanisms by which soy prevents breast cancer. Results provide strong rationale for increased biochemical and biological analyses of diets and dietary factors exhibiting these molecular actions, which have potentially significant health benefits for generations of women.

Early blueberry consumption dramatically increases bone quality
Osteoporosis is a major age-related disease with a high cost to the health care system. One way to push osteoporosis to an older age and reduce health care costs is to have a greater peak bone mass at the age when bone usually starts to decline, such as at menopause for women.  The higher the peak bone mass, the greater the age at which bone loss would be sufficient to increase fracture risk. Scientists at the Arkansas Children’s Nutrition in Little Rock, AR have been examining the ability of different dietary factors to increase bone formation and peak bone mass early in life.  They found that blueberries were highly effective in increasing bone density (increased total bone mass) and is due to the phenolic acid metabolites of blueberry pigments which stimulate bone formation. These results indicate that increasing berry consumption in children’s diet may be a major means of increasing bone quality and reducing later risk of osteoporosis and suggest the potential for development of phytochemical-based medicines for treatment of bone disease.  

Effects of Eating breakfast on Behavioral Regulation and Brain Activity in Preadolescents
There are very few studies documenting the effects of the USDA School Breakfast and Lunch programs on brain function and behavioral dynamics important for learning in healthy children. Scientists at the Arkansas Children's Nutrition Center have addressed this question in the largest controlled study of its type to date and have shown that well-nourished preadolescents who ate breakfast showed performance benefits and more efficient brain activity related to learning processes (i.e., attention and decision making) compared with those who skipped breakfast. These results are important in showing immediate neurophysiological and behavioral effects of a short-term variation in morning nutrition (skipping or eating breakfast) in well-nourished preadolescents. This information supports the benefits of consuming breakfast for processes is important in learning.

Food Allergy
The Food Allergy Research Program at ACHRI is part of the NIH-funded, five-center, Consortium of Food Allergy Research (CoFAR).  The NIH CoFAR Program has completed its first five years of funding (7/05-6/10) and has recently been awarded approximately $30 million for an additional five years of funding through 2015. The Food Allergy Research Program also conducts clinical trials for the development of novel forms of immunotherapy and treatments for food allergy, such as epicutaneous immunotherapy, sublingual immunotherapy and Chinese Herbal Therapy for food allergy. Particular successes have been noted in the development of oral immunotherapy for peanut allergy through collaboration with investigators at other institutions.  This work will continue to focus on peanut allergy while expanding to other food allergens in children and adults.  These research studies have garnered national media and scientific interests in recent years due to exciting advances in therapies for food allergic children and adults that provide hope for better disease outcomes for food allergic patients.  Funding for these projects is through the NIH/NIAID, the National Peanut Board, the Food Allergy Initiative, the Dorothy and Frank Robins Family, and the Alex Orum Peanut Allergy Research Fund. 

Injury Prevention
Researchers in the Injury Prevention Center began a project, Drive by the Rules Keep the Privilege , funded by the National Highway Traffic Safety Administration, aimed at increasing parental responsibility in setting and reinforcing proven strategies to decrease the risk of motor vehicle injuries in teens, specifically: 1) restricting underage drinking, 2) increasing seat belt use for all occupants of the vehicle, and 3) enforcing principles of a graduated driver’s license within the family and community, including restrictions on nighttime driving, the number of passengers riding with a teen driver, and cell/smart phone use while driving.   An external evaluation contractor will conduct observational surveys and surveys of parent/teen dyads at Division of Motor Vehicles offices and will review citation data from local law enforcement agencies in the two communities to determine effectiveness. 

Pediatric Pharmacology
In fiscal year 2010, the Pediatric Pharmacology Research Unit (PPRU) at Arkansas Children’s Hospital participated in over 20 clinical trials involving 170 children and adolescents. These clinical trials focused on a number of drug treatments from a wide variety of disease areas, including drugs for the treatment of infections, high blood pressure, gastritis, epilepsy, organ transplants, and pain.

Influence of Diet in Early Childhood Development
Scientists at the Arkansas Children's Nutrition Center (ACNC) have compared brain responses to speech sounds in infants who were breast fed or formula fed (milk-based or soy formula) when they were 3 and 6 months old. They found that speech sounds were processed faster in breast-fed than formula-fed infants, but discrimination of different speech sounds was greatest in soy-fed infants. These findings are of general developmental significance in showing the extent to which language sounds are automatically evaluated in early stages of cortical processing in infants, that these processes are differentially modulated by infant diet and, the absence of diverse influences of soy formula on brain function processes during the first postnatal 6 months. These findings provide comparative information regarding infant diet to parents and physicians and should help reduce the concerns of parents and industry regarding the use of soy formula.

Impact of early diet on reproductive organ development in infants 
Soy infant formula is either banned or restricted in some countries because of concerns that it may have adverse effects on reproductive organ development in children.  Scientists at the Arkansas Children’s Nutrition in Little Rock, AR imaged the reproductive organs (ovary, breast, uterus, testis, and prostate) in infants that were fed breast milk, milk formula or soy formula using ultrasonography and determined the shape and size of each organ.  We found that infants in all three groups grew at essentially the same rate and the reproductive organs of infants fed soy formula did not differ from those of breast-fed infants.  The results suggest that soy formula does not adversely affect reproductive organ development, and thus fail to support restricted use of soy formula.

Effects of Infant formula vs Breast Feeding on Bone Formation in Neonates
Although breast feeding is the gold standard for infant nutrition, the majority of infants in the U.S. are formula fed (cow milk-based or soy-formula). It is important to know if the diet (breast milk or commercial formulas) produces significant differences in health outcomes of American infants.  Scientists at the Arkansas Children’s Nutrition Center have conducted studies comparing bone development in a piglet model of breast and formula feeding. Interestingly, piglets fed either cow-milk or soy formula (the same formula sold for infants) had better quality bone than breast-fed piglets. This appears to be due to as yet unidentified factors in milk and soy which stimulate bone growth. These results suggest that milk formula or soy formula consumption during early development may increase bone mass and this may lead to greater peak bone mass in adults and lower the risk of osteoporosis in later life.  Studies are underway to determine if similar results occur in children.

Maternal Overweight Programs Multiple Aspects of Energy Balance in Offspring
The worldwide epidemic of obesity has developed rapidly over only a few generations and the correlation between maternal obesity and childhood obesity is much stronger than with paternal obesity. This suggests that additional factors associated with the intrauterine environment of overweight women may predispose their children to obesity. Data from scientists at the Arkansas Children’s Nutrition Center suggest that fetal exposure to an overweight mother during pregnancy programs several hormonal systems that regulate energy balance in babies and causes fat accumulation. Overfeeding female rats prior to breeding with lean males produces male offspring that: make more fat; store more fat in their liver; are less able to degrade (breakdown) body fat; become obese; and have increased levels of blood hormones, such as insulin and  the fat derived hormone adiponectin. These data suggest that overweight pregnant rats send signals to the fetus that permanently change the way their offspring metabolize energy.  This has important implications for strategies to prevent childhood obesity in children of overweight or obese women.

Soy protein consumption reduces body fat stores and fatty liver
Obesity continues to be a health problem and increased storage of fat in the liver is a major consequence of obesity that can result in frank liver disease.  The incidence of pediatric non-alcoholic steatohepatitis (fatty liver disease) is increasing in the United States along with childhood obesity and treatment or preventive measures are needed.  We studied the effects of soy protein in rats and found reduced body weight gains, lower total body fat, and decreased liver fat stores.  These data suggest that diets containing soy protein could prevent fat buildup in the liver and perhaps be important as a treatment for children with extreme fatty liver disease.

Early fruit consumption and breast health
Breast cancer risk is highly modified by environmental factors including diet.  Foods high in antioxidants, such as fruits, may reduce the incidence of adult onset of chronic diseases, including breast cancer. Scientists at the Arkansas Children’s Nutrition Center in Little Rock, AR evaluated blueberry effects on development of the mammary gland using rat and mouse models. They found that early exposure (in utero/prepubertal) to blueberry-supplemented diets promoted mammary gland differentiation (maturation) in rats and mice, as well as increased production of the “tumor suppressors proteins” (PTEN and E-cadherin). These results provide strong support for the healthy benefits of increased fruit consumption at an early stage of mammary development for breast cancer protection.         

Rice diet and prevention of atherosclerosis
Consumption of a traditional Asian diet high in soy and rice has been implicated in the lower incidence of cardiovascular disease in Asia than in the Western countries. Scientists at the Arkansas Children’s Nutrition Center in Little Rock, AR tested whether a rice-based diet inhibits the initiation of atherosclerosis using a hyperlipidemic mouse model. Rice-fed mice showed significantly reduced atherosclerotic lesions compared with control diet-fed mice. The mechanisms of action appear to involve antioxidant properties of rice.  These important observations may help to design a nutritional approach to prevent atherosclerosis. Future studies at the ACNC are aimed at finding the mechanism by which rice prevents cardiovascular disease.

Nursing Research
The Arkansas Children’s Hospital nursing staff were very productive in research and evidence-based practice in the 2010 fiscal year. ACH nurses led 44 projects that generated knowledge through research or translated research into practice through evidence-based practice initiatives. Staff shared their findings and clinical expertise through 5 journal articles and 49 presentations.  
Jaye Henderson, MSN, RN completed a study examining the effect of hardiness education on hardiness and burnout in inpatient nurses. She learned that the education was effective in improving hardiness and reducing burnout. This provides insight into interventions that may help nurses cope with the stresses of inpatient care.

Luann Jones, DNP, APN, NNP-BC continues her work evaluating an oral feeding pathway in the NICU. At 3 months post pathway implementation, there was a trend toward a shorter transition to oral feedings and reduced length of stay. The one year follow-up data are now being collected.
Joanne Kaye, RN, CPN, Jaye Henderson, MSN, RN and Carol Wright, BS, MAHA, RN and the ACH 4B, 4C, 3E and 4E teams completed a project piloting hourly rounds on the inpatient medical-surgical units. Parent satisfaction with nursing care improved on the inpatient units. Broader implementation of hourly rounds at ACH is now under way.

Anita Mitchell, PhD, APN a UAMS College of Nursing investigator, completed a pilot study in the NICU to examine physiologic effects of eye examinations for retinopathy of prematurity (ROP). She learned that there was a significant increase in apnea events in the 24-48 hours after an eye examination. This has important implications for the safety of infants before and after eye examinations, a common NICU procedure.
Angie McJunkins, RN, CPN in collaboration with Drs. Sunny Anand, Whit Hall and Angela Green completed a randomized trial of two pain assessment tools in children with cognitive impairment. The team learned that pain assessment tools that have been validated in children with cognitive impairment are more likely to detect pain than tools designed for the general population. This has important implications for measuring pain in this vulnerable population of children.

Trenda Ray, PhD, APN, PNP-BC completed research focusing on the association between self-efficacy and physical activity in children with congenital heart disease. Only 38% were meeting CDC guidelines for physical activity. There was a significant association between self-efficacy and physical activity participation: children with higher self-efficacy were more likely to be physically active. Of note, over 30% of the children were overweight or obese. This research provides insight into cardiovascular risk factors in children with congenital heart disease.