An estimated 30-40,000 children are born each year with congenital heart disease (CHD) and often require surgical intervention during the first year of life. A dramatic reduction in surgical mortality has been accompanied by increasing recognition of adverse neurodevelopmental sequelae. Following repair of CHD, there is a pattern of neurodevelopmental sequelae characterized by cognitive dysfunction; speech and language abnormalities; impaired executive function; impaired visual-spatial and visual-motor skills; attention deficit disorder; and learning disabilities. Need for early intervention, rehabilitation, and special education reduces the quality of life for the children and their families. Central nervous system (CNS) injury in children with CHD is the result of an interaction of patient factors and environmental influences. Cerebral ischemia during surgical repair has been proposed to be a primary mechanism. The type of support during surgery (deep hypothermic circulatory arrest [DHCA] or continuous cardiopulmonary bypass) has been identified as a risk factor. However, these factors do not explain the incidence or pattern of neurodevelopmental dysfunction suggesting that other patient-specific factors may be determinants of CNS injury. Genetic polymorphisms which may increase susceptibility to CNS injury have not been explored in children with CHD. Apolipoprotein-E (APOE) is a regulator of cholesterol metabolism. There is an association between Alzheimer's Disease and the APOE-4 allele. APOE genotype is a determinant of neurologic recovery following CNS injury. There is an association of APOE genotype with cognitive decline after cardiac surgery in adults. In October 1998, we initiated a study to evaluate neurologic dysfunction and APOE genotype in infants with CHD. Two hundred and forty-four infants have undergone one-year evaluation. The findings demonstrate a significant effect of the APOE c2c2 and c2c3 genotypes to predict a worse outcome as assessed by the Psychomotor ? Developmental Index (PDI) of the Bayley Scales of Infant Development. We propose to evaluate this cohort at 4 years of age to test the hypothesis that APOE genotype predicts cognitive impairment, impaired attention and executive function, as well as impairment of fine motor and visual-motor skills. ? ?
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