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NICU Clinical Research. Infant Body Composition Reference Data for Preterm Infants Ellen Demerath, Ph.D., Sara Ramel, MD, and Michael Georgieff, MD

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spotlight on research

NICU Clinical Research

Infant Body Composition Reference Data for Preterm Infants Ellen Demerath, Ph.D., Sara Ramel, MD, and Michael Georgieff, MD

Early infancy is a very critical growth period. Changes in body composition during this time may have an effect on future obesity risk and potentially cognition. Research in this area may help better care for premature babies in the future by matching the clinical treatment and nutrition of infants to their individual needs. Our study uses air displacement plethysmography (PEA POD) to determine percent body fat and lean muscle mass in preterm infants (30 – 36 weeks) shortly after birth. This data will be used to create reference curves, similar to the growth curves that are currently used to plot weight, length and head circumference. This study is funded by COSMED USA, Inc.

The Role of Linear Growth and Fat-Free Mass Gain in Determining Cognitive Outcomes in Extremely Preterm Infants

Sara Ramel, MD, Michael Georgieff, MD, and Ellen Demerath, PhD

Infants experiencing catch-up growth are at risk for disproportionate growth (gaining weight without gaining appropriate height) which predisposes them to future obesity, metabolic syndrome and cardiovascular disease. These infants may also be at risk for further cognitive delay. Careful monitoring of linear growth (how the baby grows in length) and fat-free mass gains, along with strategic nutrition management, may improve long-term outcomes in this vulnerable population. This study aims to better understand the relationship between linear growth, fat-free mass gains and later cognition. We hope to also identify nutritional changes that might affect fat-free mass gains during and after initial hospitalization and cognition at 1 year corrected age in very low birth weight (less than 3 pounds, 5 ounces) preterm infants. This study is funded by the Amplatz Scholar Award through the Minnesota Medical Foundation.

Spotlight on Research

Hypothalamic-Pituitary-Adrenal Axis Stress Responses in Small for Gestational Age Infants

Erin Osterholm, MD and Megan Gunnar, PhD

The purpose of this study is to better understand how newborn infants respond to stressful situations. We know that conditions in pregnancy that lead to smaller than expected infant size may affect several adult medical problems including heart disease, high blood pressure, and diabetes. These problems have been linked to increased levels of the hormone cortisol, which helps the body deal with stress. In this study, we non-invasively measure the levels of the hormone cortisol in saliva from the infant’s mouth before and after usual events in the NICU like blood draws and physical exams. We hope to learn more about how the hormone systems of infants are affected by the day to day medical care they require, so that we can minimize some of these changes in the future. We will also study whether these changes contribute to how infants grow muscle and fat as they get older. This study is supported by a grant from MedImmune for Follow-up Care of the Preterm Infant.

Preterm Preschool Executive Function (PPEF) Project Jane Brumbaugh, MD, Kathleen Thomas, Ph.D., and Amanda Hodel

Neurodevelopment and cognitive function are among the most important outcome measures following preterm birth. The impact of moderate to late preterm birth (birth at 32-36 weeks gestation) on executive function remains incompletely defined. Executive function refers to a collection of interrelated brain processes that control purposeful, goal-oriented behaviors, including working memory, inhibitory control, sustained attention, and planning. The objective of this study is to characterize executive function in children born moderate to late preterm at 4 years of age. Children complete tasks designed to challenge the domains of executive function. Results of this work will increase our understanding of executive function, dysfunction, or delay in development in moderate to late preterm children. This study is funded by the Center for NeuroBehavioral Development at the University of Minnesota.

Early Evaluation of Memory Function in Term Survivors of Hypoxic-ischemic Encephalopathy Katie Pfister, MD

Babies with hypoxic-ischemic encephalopathy (HIE) suffered from a period of time with low or no blood flow and/or oxygen to the brain around the time of birth. Because of this injury to the brain, these babies are at risk for developmental problems ranging from mild delays and learning disabilities to cerebral palsy and severe intellectual delay. During infancy, it is difficult to accurately predict the developmental outcome of babies with HIE, especially those with a more mild or moderate injury. Many of the infants who appear to have typical development as infants and toddlers go on to have difficulties once they get to school age, specifically with learning, attention and memory. The brain is still developing for the first two years of life, so it would be ideal to find learning problems early in life when the infant may benefit more from therapy. This study will use a special type of EEG called event-related potentials (records the electrical activity of the brain) to evaluate whether or not abnormal memory function is detectable in the first few weeks of life in babies with HIE and whether or not any abnormality remains or resolves by one year of age.

Growth and Development

Lungs

Laryngeal Mask Airway for Surfactant Administration Kari Roberts, MD

Respiratory distress syndrome (RDS) is a disease process where premature infant lungs are not able to produce a detergent-like substance, called surfactant, which coats the airsacs and helps keep them open. Current mainstays of treatment for RDS include mechanical ventilation (breathing machine), nasal continuous positive airway pressure (nCPAP) (prongs in the nose which push air into the lungs and help keep the airsacs open) and/or surfactant medication. Administration of surfactant currently requires placement of a breathing tube so the surfactant medication can be delivered into the lungs and the infant being on a breathing machine afterwards. This study investigates using a different device, called a laryngeal mask airway (LMA) to administer surfactant into the lungs of infants on nCPAP. If proven effective, infants with RDS may be able to benefit from surfactant medication while avoiding having a breathing tube placed and being on a breathing machine. Infants may be eligible for this study if they are born between 28 and 36 weeks gestation and have signs of RDS. This study is funded by the Minnesota Medical Foundation and Children’s Hospital Association.

TOLSURF: Trial of Late Surfactant to Prevent Bronchopulmonary Dysplasia (BPD) Catherine Bendel, MD and Tom George, MD

Bronchopulmonary dysplasia (BPD) is the chronic lung disease that develops in some preterm infants who require prolonged ventilation (breathing machine). Many different therapies have been tried to decrease the risk of developing BPD, including surfactant (a detergent-like substance in the lungs) therapy and inhaled nitric oxide (iNO) (a natural substance made in the lungs and blood vessels) therapy individually; however, no single therapy has been effective. The purpose of this multi-center study is to see if giving additional doses of surfactant combined with iNO during the first month of life will improve lung function and decrease the risk of BPD. Infants who may qualify to participate are ≤ 28+0 weeks gestation at birth and day of life 7 – 14 at the time of enrollment. Funding for this study is provided by the National Heart, Lung and Blood Institute.

Heart

Pulse Oximetry Screening for Critical Congenital Heart Disease Lazarus Kochilas, MD, Jamie Lohr, MD, and Ted Thompson, MD

This study is designed to detect infants with critical congenital heart disease before hospital discharge and to detect problems related to confirming the diagnosis (performance of an echocardiogram, reading of an echocardiogram, communication of results). This study uses pulse oximetry (a non-invasive method of measuring the percentage of haemoglobin (Hb) which is saturated with oxygen) to screen for possible congenital heart disease in healthy newborn infants ≥35 weeks gestational age. This study is enrolling infants from the Newborn Nurseries at the Fairview System Hospitals (Lakes, Red Wing, Ridges, Southdale and UMACH) and is a forerunner to screening being performed at the state and national levels. Support for this study is provided by the Fairview Health System and University of Minnesota Amplatz Children’s Hospital.

because our smallest patients deserve our biggest brains
Because our smallest patients deserve our biggest brains.

NICU Clinical Research

IntestinalTract

SPOT (Spotting Perforations on Time) Nicole Birge, MD

Premature infants are at risk for developing inflammation of their intestines, which may then lead to a perforation (hole) in the intestines. In some infants, perforation may occur without any signs of inflammation. A perforation of the intestines may be difficult to diagnose using x-rays, which can cause a delay in diagnosis and treatment. This study will determine if a blood test can diagnose perforation in premature infants. Infants are eligible to participate if they weigh less than 1000 grams (2 pounds, 3 ounces) at birth. This study is funded by the Children’s Hospital Foundation and the Minnesota Department of Health.

Developmental Changes in Intestinal Microflora and Inflammatory Markers in Newborns with Cyanotic Heart Disease

Caroline George, MD

The importance of developing a protective and tolerant intestinal microflora (bacteria) following birth is well established for the overall health of a newborn. How congenital heart disease and associated therapies affect the establishment of intestinal microflora in newborn infants is not known. This study will identify newborns with congenital heart disease requiring surgical repair in the newborn period as well as control age-matched infants that require hospitalization for non-cardiac reasons who are tolerating full enteral feedings (by way of the gastrointestinal tract). By evaluating changes in the bacteria in stool between babies with heart disease and those without during the first 3-4 weeks of life, we will compare the bacteria colonization patterns and measure markers of intestinal inflammation between infants. These findings might then help us to evaluate whether or not therapies that promote protective intestinal microflora are safe and effective in these infants.

Eyes

Drop ROP Inge De Becker, MD, Erick D. Bothun, MD, and Jill S. Anderson, MD

Retinopathy of prematurity (ROP) is the abnormal development of blood vessels in the retina inside the eye. ROP is common in extremely premature children, and it can sometimes lead to blindness, even with the best currently available treatment. The purpose of this multi-centric study is to learn whether giving eye drops called Betaxolol will prevent ROP from developing, or will help ROP be milder and less dangerous to a child's vision. Infants may be eligible for this study if they weigh less than 1,000 grams (2.2 pounds) at birth. This study is funded by the Smith-Kettlewell Research Institute.

eROP Study: Telemedicine Approaches to Evaluating Acute-phase ROP Erick D. Bothun, MD, Inge De Becker, MD, and Jill S. Anderson, MD

  • As mentioned above, premature babies are at risk for developing retinopathy of prematurity (ROP). The purpose of this multi-center study is to evaluate the safety, reliability and cost-effectiveness of using a highly specialized camera system called a RetCam Shuttle to take images of the retina (where the abnormal growth of blood vessels occurs in ROP) in babies who are at risk of developing sight-threatening ROP and are in need of a diagnostic evaluation by an ophthalmologist experienced in ROP. The images are then transmitted electronically to a reading center, graded, and the results are compared to a diagnostic examination performed by the ophthalmologist at the same time the images were taken. Infants who may qualify for this study weigh less than 1251grams (2 pounds, 8 ounces) at birth. This study is sponsored by the National Institutes of Health.

Bench (Lab) Research

Mechanisms of Candida albicans Invasion Cheryl Gale, MD

The fungus Candida albicans is a leading cause of life-threatening infections in premature infants. Antifungal antibiotics are effective in curing the disease in only ~50-60% of cases, thus there is a need for better therapies. Candida albicans exhibits a number of shapes and one, the long, filamentous hypha, is thought to be responsible for tissue invasion and injury in patients. This study uses molecular biology (gene knockouts and modifications) and cell biology (microscopy of hyphae during growth and invasion) to understand how Candida albicans uses changes in its shape (morphogenesis) to cause invasive disease. With this knowledge, we hope to develop improved strategies to prevent and treat fungal infections in premature infants. This work is funded by the National Institutes of Health.

Yeast (Candida) Interactions with Neonatal Mucosa and Skin Catherine Bendel, MD

As mentioned above, the yeast Candida can be a major cause of infection in the preterm infant. The source of these infections is the particular yeast that is a part of the normal flora on the baby's skin or in their intestines. Our laboratory is interested in better understanding how the yeast interacts with the mucosa/skin to adhere and colonize normally; as well as the risk factors leading to abnormal invasion, inflammation and wide-spread infection. We have both animal and tissue culture models to evaluate these interactions, with the ultimate goal of developing therapies to prevent infection from ever happening. This work is funded by the Division of Neonatology.

Neonatal Iron Deficiency Michael Georgieff, MD

Iron deficiency is one of the most common nutrient deficiencies worldwide, affecting two billion people and up to 30% of all pregnant women and their babies. We study the effect of iron deficiency in newborn babies and its effects on the developing brain, especially those areas of the brain involved in learning and memory. We are studying the mechanisms by which iron is necessary for normal growth, development and interconnection of the nerves in the brain, why iron deficiency early in life leads to long term learning and memory problems, and whether other dietary supplements to either the mother during pregnancy or the baby after delivery can lessen the effects of early iron deficiency. These studies are funded by the National Institutes of Health, the Minnesota Medical Foundation, and Alfred and Ingrid Lenz Harrison.

Nutrition and Brain Development Raghavendra Rao, MD

Nutrients such as iron and glucose are important for normal brain growth and function. Deficiency of these nutrients is common in babies who are born premature or after certain pregnancy complications. Our research focuses on the effects of such deficiencies on the brain. Using powerful magnets (approximately 6 times more powerful than those used in clinical practice) and molecular methods, we study how nutritional deficiencies affect brain development. With this knowledge, we hope to develop strategies for optimizing brain development in babies. This work is funded by the National Institutes of Health.

Fetal and Neonatal (Developmental) Origin of Adult Diseases Phu V. Tran, Ph.D.

Early-life environment (i.e., micronutrient deficiency, hypoglycemia, intrauterine growth restriction, hypoxic-ischemic encephalopathy) can have long-term impact on adult health by increased risk of obesity, diabetes, hypertension, cardiovascular disease, neurocognitive decline. Utilizing preclinical models, we investigate how early-life environment causes permanent change in expression of molecules (e.g., proteins, hormones) that maintain physiological homeostasis, including stress responses, fear and anxiety, and learning and memory. In particular, we focus on growth factors that play critical roles in the neuroendocrine system, a major regulatory system that can be influenced by early-life environment. With this knowledge we hope to uncover molecules that can be targeted for therapeutic development and provide insights into how fetal/neonatal conditions contribute to the risk of adult diseases. These will be essential in developing strategies for treatment and prevention of adulthood pathophysiologies. This work is supported by the Minnesota Medical Foundation, Viking’s Children’s Fund, Center for NeuroBehavioral Development at the University of Minnesota Seed Grant, and the National Institute of Child Health and Human Development.