Preventing Brain Injury in Infants With Congenital Heart Disease

Infants with cyanotic congenital heart disease undergoing surgery in the neonatal period have a high rate of brain injury resulting in seizures, stroke, cerebral palsy, and neurodevelopmental delays. Neuroimaging abnormalities are found in 30% to 60% of cases and neurodevelopmental impairments occur in more than half of these children. The mechanisms of brain injury in these children are not fully understood. Experimental animal models have shown that the abundant release of glutamate in the brain during hypoxic-ischemic insult results in brain injury. Blocking glutamate receptors by administration of the anticonvulsant topiramate has been shown to prevent such injury in animal studies. This study is an open pilot trial of peri-operative topiramate administration to infants with cyanotic congenital heart disease to test the feasibility of this approach and generate preliminary data about markers of brain injury (serum S100B levels and urine metabolomics) and neurodevelopment at 18 months of age. If the approach is feasible and the preliminary data are encouraging a larger efficacy trial will be designed. Although topiramate has been used in neonates and infants to treat seizures and in a pilot study in term infants with hypoxic-ischemic encephalopathy, this is the first study of its effects on markers of brain injury and neurologic outcomes in infants with cyanotic congenital heart disease.

Inclusion criteria

• Age less than 2 months
• Cyanotic congenital heart disease requiring surgery

Exclusion criteria

• Genetic syndromes with high risk of neurodevelopmental delay
• Gestational age less than 35 weeks at birth
• Multiple organ failure or multiple organ anomalies