Grantor: Patient-Centered Outcomes Research Institute
Project summary: The World Health Organization reports that birth asphyxia/neonatal hypoxic ischemic encephalopathy (HIE) accounts for one million deaths annually and represents the most common cause of death and disability in neonates. Fifty percent of those are in the unstudied mild HIE spectrum. This project aims to establish the comparative effectiveness and safety of hypothermia versus normothermia in 430 infants with mild HIE representing all races born at 15 academic centers with balanced distribution of cooling practice per site existing practice standards. Engagement of families and community of those affected by HIE are central to this project.
Grantor: National Institute of Neurological Disorders and Stroke
Project summary: Hypoxic-ischemic encephalopathy (HIE) is the leading cause of newborn death and disability worldwide and presents clinically as neonatal encephalopathy that is difficult to classify within a short window after birth to inform neuroprotective interventions. Therapeutic hypothermia (TH) has dramatically improved outcomes in moderate to severe HIE when initiated within six hours of life (HOL), yet trials have not included mild HIE. The difficulties to discern the clinical severity shortly after birth and to analyze the dynamic circulation in sick newborns represent important challenges. The goal of project is to harness our novel physiological biomarkers to focus on untreated mild HIE to identify those who need treatment t. Our objective is to test dynamic biomarkers that can predict structural and functional outcomes chosen with input from stakeholders and inform physiological and metabolic disturbances specific to mild HIE.
Grantor: Eunice Kennedy Shriver National Institute of Child Health and Human Development
Project Summary: To establish unbiased measures that will differentiate developmental feeding intolerance from pathologic feeding intolerance with the goal of limiting unnecessary feeding delays, parenteral nutrition, and improving outcomes in preterm infants.
Project Summary: We are studying placental and cerebrovascular hemodynamics in fetuses with congenital heart disease (CHD) using advanced MR imaging techniques. In pregnant people with fetuses diagnosed with specific types of CHD, we are evaluating placental perfusion longitudinally to determine associated differences in placental size and histopathology. We are also studying the impact of placental perfusion on cerebral autoregulation from prenatal to the early postnatal adaptation using Doppler ultrasound and wavelet coherence analysis. This data will be used to inform a working model regarding how placental perfusion and cerebral autoregulation affect the trajectory of regional brain growth in fetuses with CHD.
Placental Hemodynamic Effects on Brain Development in Infants with Congenital Heart Disease
Grantor: American Heart Association
Project Summary: This project uses radiogenomic methodology in a prospectively recruited cohort. We are studying placental perfusion changes in pregnant people whose pregnancy is complicated by fetal CHD at two timepoints along with their associated placental transcriptomic profile. We will use this data to create candidate biomarkers of placental function in vivo and then assess their prevalence and utility in circulating maternal blood. Secondarily, we are studying how placental nutrient transporter capacity affects the trajectory of regional fetal brain development in those with CHD to begin to understand why fetuses and neonates with CHD have delayed brain maturation and smaller brain volume beginning in the second half of pregnancy.
Project Summary: Medical advances in recent years have allowed premature babies to survive at younger ages than ever before. This is the first program in Texas and one of a handful in the country. The goal is to help these babies not just survive but thrive and have the best possible future. We create an integrated Fetal and Neonatal Developmental Neuro-NICU program at UT Southwestern (UT/Children’s Health/THD Parkland) first and only Neuronicu in the state of Texas to provide excellence in care, diversity and collaboration. The expanded integrated program will lead to better care, improved neonatal outcomes across the lifespan and a competitive specialty program regionally and nationally.
Project summary: Neonatal encephalopathy (NE) resulting from birth asphyxia constitutes a major global public health burden for millions of infants every year, and despite therapeutic hypothermia, half of neonates have poor neurologic outcomes. As new neuroprotective interventions are being studied in clinical trials, there is a critical need to establish physiological surrogate markers of therapeutic efficacy, to guide patient selection and/or to modify the therapeutic intervention. A real time evaluation of the coupling of cerebral blood flow and neuronal activity “neurovascular bundle” is therefore proposed in order to determine the severity of injury and identify infants that could potentially benefit from added therapies.
Project Summary: Birth asphyxia constitutes a major global public health burden for millions of infants. Hypothermia remains the sole neuroprotective therapy available, yet as many as half of treated infants have poor outcomes. The overarching goal of the research project is to assess cerebrovascular function in a spectrum of mild, moderate and severe HIE to determine how changes in cerebrovascular function reflect the extent of cerebral injury as detected by MRI and occurrence of seizures. Dysfunctional autoregulation will be further examined in newborns with moderate to severe HIE undergoing hypothermia therapy to test how it is modulated with a deeper/longer hypothermia regimen and during the rewarming process.