CTN Research - Kaiser

Physiological Disturbances Associated with Neonatal Intraventricular Hemorrhage: Annually, nearly 5,000 extremely low birth weight (ELBW, birth weight ≤1000 g) infants in the US develop severe intraventricular hemorrhage (IVH, grades III and IV); this devastating complication of prematurity is associated with long-term adverse neurodevelopmental sequelae, such as cognitive, behavioral, and learning disabilities, as well as cerebral palsy. Unfortunately, identifying the ELBW infants who are at highest risk for developing IVH and who could benefit most from specific interventions has been difficult and based on retrospective studies. Our overall goal is to prospectively evaluate and understand disturbed physiological phenomena associated with IVH in order to predict those infants most at risk and to develop best care clinical practices that may subsequently limit severe brain injury in ELBW infants. While the etiology of IVH is multifactorial, disturbances of cerebral blood flow (CBF) and cerebral autoregulation play important roles; both are influenced by alterations of gas exchange and systemic hemodynamics associated with routine intensive care procedures. Extremes of CO2 may have deleterious effects on infants' CBF because the arterial CO2 tension (PaCO2) is a potent mediator of cerebral vascular tone and influences cerebral blood supply. Hypotension or hypertension may cause cerebral hypo- or hyperperfusion, respectively, leading to IVH in infants with impaired cerebral autoregulation by an ischemia/reperfusion mechanism. Because disturbances of PaCO2, blood pressure (BP), and heart rhythm are common in ELBW infants undergoing intensive care, our central hypothesis is that alterations and extremes of these physiological factors that influence CBF and cerebral autoregulation in ELBW infants may initiate IVH and serve as important predictors of ELBW infants most at risk of IVH, thereby allowing identification of a high-risk subgroup of infants who may benefit most from intervention.

Doppler ultrasound is a widely used non-invasive method to study neonatal cerebral hemodynamics; it was first used in newborns in 1979. Determining cerebral blood flow (CBF) velocity by ultrasound is based upon the Doppler principle where a change in the frequency of a sound wave is caused by the relative motion between an observer and a sound source. The procedure is non-invasive, safe, easily performed at the bedside without disturbing the infant, provides real-time information, and is ideal for making serial measurements from stable or sick infants. Additional advantages of using Doppler ultrasound to measure CBF velocity (an indirect measure of CBF) are that no radioactive materials or chemicals (such as xenon or nitrous oxide) are used, manipulations are not required (as with venous plethysmography), and the technique does not require alterations of oxygen concentration (as with near infrared spectroscopy). Dynamic monitoring is another important benefit of this technique because it allows continuous and instantaneous measurements of CBF velocity. Thus, this method offers a non-invasive approach to investigate how disturbances of CBF velocity in VLBW infants may be linked with brain injury.