Neonatology Research

Growth and Development

Infant Body Composition Reference Data for Preterm Infants

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

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 Effects of Illness and Nutrition on Growth and Cognition in 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) that predisposes them to future obesity, metabolic syndrome and cardiovascular disease. Higher levels of inflammation in the blood might also be associated with slower growth, particularly fat-free mass gain. These infants may also be at risk for further cognitive delay. Careful monitoring of linear growth (how your baby grows in length) and fat-free mass gains, along with strategic nutritional manipulations and reduction of systemic inflammation, may improve long term outcomes in this vulnerable population. This study aims to better understand the effects of illness and nutrition on growth and cognition in very low birth weight (less than 3 pounds, 5 ounces) preterm infants. This study is funded by The March of Dimes®.

Preterm Epo Neuroprotection Trial (PENUT Trial)

Raghavendra Rao, MD, Sara Ramel, MD, Nancy Fahim, MD, and Erin Stepka, MD

The purpose of this study is to prevent neurodevelopmental impairment associated with extreme prematurity (babies born at 24 to 28 weeks gestation). Premature infants born before 28 weeks gestational age are at high risk for developing long-term problems with their growth and development. These problems include cerebral palsy, deafness, blindness, and mental retardation. We know that premature infants are most vulnerable in the first days after birth, but their brain remains at risk for injury until they are close to their due date. A medicine called Erythropoietin (Epo) may lessen the risk of long-term developmental problems if given when the baby’s brain is at risk. This medicine is commonly used in preterm infants to help them make red blood cells. The dose used for making red blood cells has been well tested and is safe in these babies, but the dose needed for brain protection is higher. We want to find out if Epo can work to protect premature babies from having neurological problems (brain problems), and if the higher dose of Epo is safe for premature babies. This study is funded by the National Institute of Neurological Disorders and Stroke (NINDS) and is being conducted in collaboration with neonatologists at The University of Washington.

Pain Management

IV Acetaminophen for Acute Pain Management in Infants and Children (age <2 years)

Chandra Castro, MD, Kumar Belani, MD, Catherine Bendel, MD, Megan Clinton, MD, Daniel Guillaume, MD

Pain is an unfortunate part of any surgery or serious injury. This clinical study will investigate whether adding intravenous (IV) acetaminophen (the active drug in Tylenol®) to typical pain treatment will treat pain better. We hope that by adding IV acetaminophen babies will need less opioid (narcotic) pain medication. IV acetaminophen is currently used in children 2 years and older, adolescents, and adults for pain and fever. Giving acetaminophen by mouth or in the rectum is well understood in babies and children of all ages. However, less is known about the use of IV acetaminophen in children under two years of age. The Food and Drug Administration (FDA) has not yet approved the use of IV acetaminophen in children less than two years. A number of neonates and infants have already received IV acetaminophen in clinical trials. This clinical study will help us better understand how well IV acetaminophen works to treat pain, how the body of an infant handles the medication and what the proper dose for this medication is in babies. Infants born at 28 weeks gestation or later and less than 29 days old who have had recent surgery or injury may be eligible to participate. This study is funded by Cadence Pharmaceuticals, Inc.

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.

Blood

Neonatal Thrombocytopenia and Its Treatment

Michael Georgieff, MD

Thrombocytopenia (low platelet count in the blood) affects 20 to 35% of all babies admitted to the NICU and up to 70% of extremely low birth weight infants (weight less than 2 pounds, 3 ounces). Platelets are small cells in the blood that help stop bleeding. Very often, sick babies in the NICU have low platelet counts. This may cause the baby to have problems with bleeding. At this time, giving platelets through an IV is the only treatment for a low platelet count in newborn babies. In adults, however, new medications that cause the body to make more platelets have just been approved by the FDA, and are being used to treat low platelet counts. After those medications are given, the platelet count begins to go up in about 4-6 days. It is at its highest at 10 days after the start of the medicine. After 14 days it goes down to where it was before the start of the medicine. Because of this, only babies expected to have a low platelet count for at least two weeks would be good candidates to receive this treatment in the future. In about 4 out of 5 infants who have a low platelet count, it gets better before two weeks, and right now we cannot tell which babies will go on to have low platelet counts for a long time. This study will only look at how to identify babies who might do better with a new treatment in the future. Babies enrolled in this study will not receive medication or a new treatment. This study is part of a Program Project Grant sponsored by the National Institutes of Health.

Infection

Impact of Breast Milk-Acquired Cytomegalovirus Infections on Clinical Outcomes in Premature Infants

Erin Osterholm, MD and Mark Schleiss, MD

Infections with human cytomegalovirus (CMV) are common in children and babies. Most CMV infections that occur after birth do not cause illness or long-term issues, but CMV sometimes causes serious illness. Infants commonly acquire CMV infection by breastfeeding and normal term infants usually have no symptoms. In premature infants however, the spectrum of CMV disease is unknown. There is also no consensus on whether efforts should be made to prevent or treat breast milk-acquired CMV infections in premature infants. The goal of this study is to determine the rate of transmission of CMV via breast milk and the range of illness caused by CMV in very low birth weight infants in the University of Minnesota Children's Hospital NICU. This study is funded by the University of Minnesota Department of Pediatrics Cross Divisional Research Grant.

Intestinal Tract

SCAMP

Catherine Bendel, MD

The purpose of this study is to evaluate the safety and effectiveness of 4 different antibiotic treatment regimens (i.e. 4 different combinations of multiple antibiotics) for infants with complex infections involving the abdomen and intestines. The antibiotics evaluated are ampicillin, gentamicin, metronidazole, clindamycin and piperacillin-tazobactam. Each individual antibiotic is FDA-approved and commonly prescribed for infants. Currently there is not enough information about how the bodies of neonates use these antibiotics when given together, rather than individually. The study involves collecting small amounts of blood and urine to measure the pharmacokinetics of each medicine, especially in relation to what other medications are being given; as well as obtaining cultures to determine how effective the various combinations are at treating these complex infections. Ultimately, this study will also help us to understand the proper dose and combination of these antibiotics in treating our NICU patients. Infants less than or equal to 32 weeks gestational age, or greater than or equal to 34 weeks gestational age at birth, who have a complicated intra-abdominal infection may be eligible to participate in this study which is funded by a contract with the National Institutes of Child Health and Human Development and Duke University through its Duke Clinical Research Institute. Multiple NICUs across the country are participating in this study.

The Role of the Intestinal Microbiome in Neonatal Health and Disease

Cheryl Gale, MD

The microorganisms that colonize the human intestinal tract have important roles in the development of immunity and metabolism and, when out of balance, can contribute to the development of disease. In addition, in premature infants, some intestinal microbes invade the immature and fragile intestinal mucosae, going on to cause serious life-threatening infections. In this project, the kinds and amounts of microorganisms in the premature infant intestinal tract (from fecal samples in diapers) will be characterized over time and compared to clinical features of infants. In this way, microbiomes associated with healthy outcomes, and the clinical treatments associated with the establishment of these healthy microbiomes, will be discovered. Infants of any gestational age admitted to the NICU soon after birth may be eligible for this study. This research is funded by the Minnesota Vikings Children’s Fund and the Division of Neonatology.

Bench (Lab) Research

Discovery of Strategies to Prevent Fungal Disease in Premature Infants

Cheryl Gale, MD

Candida species cause life-threatening fungal diseases in immunocompromised patients such as premature infants. Candida normally colonizes the intestinal tract and can invade into patients when their intestinal barrier is weakened by inflammation or immaturity. The goal of this research is to understand how the presence of fungal and bacterial organisms that normally live within the intestine (the intestinal microbiota) might increase the risk for Candida invasion and to learn how Candida penetrates into infant intestinal cells. With the knowledge gained from these studies, we hope to discover new therapies that prevent fungal invasion and fungal-associated diseases in premature infants and, in the future, other at-risk patient populations. This work is funded by the Minnesota Vikings Children’s Fund, the Minnesota Medical Foundation and the Division of Neonatology. 

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.

Inflammation and Brain Development

Tate Gisslen, MD

Infection and inflammation during pregnancy are the cause of nearly half of premature births. After birth, inflammation continues to affect these babies. Inflammation during this important time in their brain development might lead to long-term learning and memory problems. Our research focuses on discovering the mechanisms by which inflammation interferes with normal brain development so that we may find methods to improve long-term learning outcomes in these babies. This work is funded by the Minnesota Vikings Children’s Fund and the Division of Neonatology.

Fetal and Neonatal (Developmental) Origin of Adult Diseases

Phu V. Tran, PhD

Early-life environment (i.e., micronutrient deficiency, hypoglycemia, intrauterine growth restriction, hypoxic-ischemic encephalopathy) can have a long-term impact on adult health by increasing the risks of obesity, diabetes, hypertension, cardiovascular disease, and 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, the Minnesota Vikings Children’s Fund, a Center for NeuroBehavioral Development at the University of Minnesota Seed Grant, and the National Institute of Child Health and Human Development.