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