Preventing Brain Injury in Newborns With Congenital Heart Disease

Abstract

Miller, MDCM, MAS; on behalf of aCCENTBackground and Purpose-Newborns with congenital heart disease are at high risk for brain injury and adverse neurodevelopmental outcomes. MRI enables the objective determination of the severity of brain injury in critically ill newborns with congenital heart disease. We will rationalize the use of MRI as a surrogate for neurodevelopmental outcome and describe novel randomization techniques that can be used in trials in this population. Methods-This article describes the evidence for the use of MRI and the link with neurodevelopmental outcome established in newborns. We also discuss the use of adaptive randomization techniques for future clinical trials in newborns with congenital heart disease. These strategies will be highlighted using an example. Results-Brain injuries occur with high frequency in newborns with congenital heart disease. It is not until school age that the full extent of neurological sequelae becomes apparent and the rapid pace of innovation in neonatal cardiac surgery prevents timely evaluation of changes in care. MRI provides a timely, safe, and reliable outcome measure and has been extensively studied in newborns with other conditions in which the link between brain injury and neurodevelopmental outcome has been established. Clinical trials using MRI as an outcome measure as well as adaptive randomization can improve the efficiency of such trials. Conclusions-Clinical trials of brain protection are urgently needed in newborns with congenital heart disease given the unacceptable frequency of brain injury in this population; MRI provides an early surrogate marker of long-term neurodevelopmental outcome and adaptive randomization can be used to improve the efficiency of these clinical trials. Key Words: brain injury Ⅲ congenital heart disease Ⅲ MRI Ⅲ neurodevelopment Ⅲ randomized, controlled trials E xperts have called for large clinical trials in the prevention of pediatric strokes based on the example set by pediatric oncology groups; oncology clinical trials have vastly improved the survival and outcomes of pediatric oncology survivors. 1 The incidence of stroke in the newborn is 20 per 100 000 live births and leads to a high risk of significant long-term neurological impairments for survivors, 2 including cerebral palsy, 3 cognitive deficits, visual disturbances, and epilepsy. 4 MRI is increasingly being used to detect stroke in the newborn. A number of imaging features of stroke are now recognized as predictors of adverse neurodevelopmental outcome. 3,5 Newborns with congenital heart disease (CHD) are at increased risk for brain injury and adverse neurodevelopmental outcomes. High-resolution MRI and diffusion tensor imaging enable us to objectively determine the severity of brain injury in these newborns. Periventricular leukomalacia and neonatal strokes have both been reported to be the most significant lesions in terms of severity and incidence in infants that undergo CHD repair 6,7 ; modifiable risk factors have been identified for both giving the ho...

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