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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL071834-04
Application #
7059314
Study Section
Special Emphasis Panel (ZRG1-RPHB-3 (01))
Program Officer
Pearson, Gail D
Project Start
2003-08-01
Project End
2008-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
4
Fiscal Year
2006
Total Cost
$749,952
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Grasty, Madison A; Ittenbach, Richard F; Knightly, Carol et al. (2018) Hearing Loss after Cardiac Surgery in Infancy: An Unintended Consequence of Life-Saving Care. J Pediatr 192:144-151.e1
Kim, Daniel Seung; Li, Yatong K; Kim, Jerry H et al. (2018) Autosomal dominant mannose-binding lectin deficiency is associated with worse neurodevelopmental outcomes after cardiac surgery in infants. J Thorac Cardiovasc Surg 155:1139-1147.e2
Schultz, Amy H; Ittenbach, Richard F; Gerdes, Marsha et al. (2017) Effect of congenital heart disease on 4-year neurodevelopment within multiple-gestation births. J Thorac Cardiovasc Surg 154:273-281.e2
Bean Jaworski, Jessica L; Flynn, Thomas; Burnham, Nancy et al. (2017) Rates of autism and potential risk factors in children with congenital heart defects. Congenit Heart Dis 12:421-429
Diaz, Laura K; Gaynor, J William; Koh, Shannon J et al. (2016) Increasing cumulative exposure to volatile anesthetic agents is associated with poorer neurodevelopmental outcomes in children with hypoplastic left heart syndrome. J Thorac Cardiovasc Surg 152:482-9
Kim, Daniel Seung; Kim, Jerry H; Burt, Amber A et al. (2016) Burden of potentially pathologic copy number variants is higher in children with isolated congenital heart disease and significantly impairs covariate-adjusted transplant-free survival. J Thorac Cardiovasc Surg 151:1147-51.e4
Gaynor, J William; Ittenbach, Richard F; Gerdes, Marsha et al. (2014) Neurodevelopmental outcomes in preschool survivors of the Fontan procedure. J Thorac Cardiovasc Surg 147:1276-82; discussion 1282-1283.e
Kim, Daniel Seung; Kim, Jerry H; Burt, Amber A et al. (2014) Patient genotypes impact survival after surgery for isolated congenital heart disease. Ann Thorac Surg 98:104-10; discussion 110-1
Gaynor, J William; Jarvik, Gail P; Gerdes, Marsha et al. (2013) Postoperative electroencephalographic seizures are associated with deficits in executive function and social behaviors at 4 years of age following cardiac surgery in infancy. J Thorac Cardiovasc Surg 146:132-7
Kim, Daniel S; Stanaway, Ian B; Rajagopalan, Ramakrishnan et al. (2012) Results of genome-wide analyses on neurodevelopmental phenotypes at four-year follow-up following cardiac surgery in infancy. PLoS One 7:e45936

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