My research focus has been the effects of insufficient oxygen (hypoxia) and blood flow (ischemia) on the brain of infants born at term or near term. If severe enough, hypoxia-ischemia can lead to serious brain injury and ultimately delayed development and cerebral palsy. Hypoxia-ischemia represents a condition in which brain development has been normal until the time of hypoxia-ischemia. Effective treatments could minimize the extent of injury; my research has centered on brain cooling as a potential therapy for this condition.

Institutions

WIH

Research Description

My major area of research is the modification of brain injury by temperature. I have been involved in animal investigations to delineate the neuroprotective effects of reductions of brain temperature (2-3°C), the effects of modest brain cooling on brain metabolic rate and cerebral blood flow, and the thermal characteristics of regional brain during cooling. The animal investigations that I have completed have provided important background work for the recently completed clinical trials of reduction in brain temperature as a neuroprotective strategy following perinatal asphyxia. I have been extensively involved in one of the two largest trials of brain cooling conducted by the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network. This trial has now been completed, the primary outcome has been published, and I am currently working on the analysis of important secondary outcomes. I have been using the data of this trial to investigate the potential deleterious effects of elevated temperatures in infants with hypoxia-ischemia and given routine care following birth. I am involved in determining the utility of the amplitude integrated EEG as a prognostic tool for neurodevelopment. The latter information will help determine if the amplitude integrated EEG is a good diagnostic tool for identification of potential candidates for future trials of neuroprotective interventions.

I am presently the Principal Investigator for the Brown site of the NICHD Neonatal Research Network, and I coordinate all Network studies ongoing in the Neonatal Intensive Care Unit of Women and Infants' Hospital. The Neonatal Network is a consortium of 16 academic centers that pool their patients for the conduct of clinical investigations. Current studies include a randomized trial of different modes of ventilator support to reduce the extent of chronic lung disease among infants < 28 weeks gestation, a randomized trial of different oxygen saturation goal range to reduce the extent of retinopathy of prematurity among infants < 28 weeks gestation, new modalities to diagnose systemic candida infections, and pilot studies to gather preliminary data for a trial of the use of inositol to reduce the extent of retinopathy of prematurity among infants < 28 weeks gestation. I am on multiple working study groups within the Network to plan and implement future studies. In addition to the studies listed above, the Network maintains an important database of morbidity and mortality among very low birth weight infants (birth weight < 1500 grams) and is linked to neurodevelopmental outcome at 18-22 months of corrected age. I have been involved in studies to use this database and examine short-term outcomes as a function of admission temperature to the Neonatal Intensive Care Unit, neurodevelopmental outcome of infants with a normal cranial ultrasound, and the neurodevelopmental outcome of infants undergoing CPR at birth.

My final area of research has been collaborative research with investigators at the University of Texas Southwestern Medical Center and the Thermotek Corporation to develop new cooling devices to facilitate brain cooling with less variability in body temperature. This work involves pilot studies in animals (being conducted in Dallas) and ultimately application to infants undergoing cooling.

Awards

2005 Master of Arts ad eundem, Brown University, Providence, RI

Affiliations

Texas Perinatal Association, 1981
Dallas County Medical Society, 1987
Society for Pediatric Research, 1988
Texas Pediatric Society, 1992
American Pediatric Society, 1995
Fellow, American Academy of Pediatrics, 2004

Funded Research

1. Principal Investigator, University of Texas Southwestern Medical Center, 2 S07 RR05426-20 Biomedical Research Support Grant, "Newborn Piglet Brain Blood Flow: An Evaluation of Regional Differences", July 1981-June 1982.


2. Principal Investigator, American Heart Association, No. 83714, "Cerebral Hemodynamics of Sodium Bicarbonate in Newborn Swine", July 1983-June 1985.


3. Principal Investigator, National Institutes of Health, No. 1-R23-NS-22398, "Cerebrovascular and Metabolic Effects of Brain Ischemia", September 1985-August 1988.


4. Co-Investigator, National Institutes of Health, No. 1R01-HD-20720, Fetal Hormonal Adaptation to Intrauterine Stress", July 1986-June 1989.


5. Principal Investigator, United Cerebral Palsy, No. R-411-91, "Is Modest Hypothermia Beneficial for Ischemic Neonatal Brain", October 1, 1991-September 30, 1993.


6. Principal Investigator, United Cerebral Palsy, No. R-411-93, "Neonatal Neuroprotection Provided by Modest Hypothermia", October 1, 1993-September 30, 1995.


7. Co-Investigator, National Institutes of Health, No. 5-U10-HD21373, "Multicenter Network of Neonatal Intensive Care Units," April 1999-March 2001.


8. Consultant, Principal Investigator, Myra Wyckoff, M.D., Neonatal Resuscitation Program, "Randomized Controlled Trial of Albumin or Normal Saline on Resuscitation in an Asphyxiated Hypotensive Neonatal Model", January 2002-January 2003.


9. Co-Investigator, National Science Foundation, No. CTS50222504, Principal Investigator, Yildiz Bayazitoglu, PhD, "Thermal Modeling of the Head and Neck, October 2002-January 2004.


10. Principal Investigator, National Institutes of Health, "Multicenter Network of Neonatal Intensive Care Units", April 2001-March 2006, No. 1-U10-HD40689-03 (PI Role 2001-2003).


11. Co-Investigator, ThermoTek, Inc., "Comparison of ThermoTek and Cincinnati Sub-Zero Cooling Systems," October 2005–December 2005.


12. Co-Principal Investigator, NICHD "Multicenter Network of Neonatal Intensive Care Units", April 2001–March 2006, No. 5-U10-HD027904-13 (current year).

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