Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery

J. William Gaynor, Marsha Gerdes, Elaine H. Zackai, Judy Bernbaum, Gil Wernovsky, Robert R. Clancy, Mark F. Newman, Ann M. Saunders, Patrick J. Heagerty, Jo Ann D'Agostino, Donna McDonald-McGinn, Susan C. Nicolson, Thomas L. Spray, Gail P. Jarvik

Research output: Contribution to journalArticlepeer-review

194 Scopus citations

Abstract

Background: There has been increasing recognition of adverse neurodevelopmental sequelae in some children after repair of congenital heart defects. Even among children with the same cardiac defect, significant interindividual variation exists in developmental outcome. Polymorphisms of apolipoprotein E have been identified as a risk factor for worse neurologic recovery after central nervous system injury. Methods: A single-institution prospective study of patients ≤6 months of age undergoing cardiopulmonary bypass for repair of congenital heart defects was undertaken to evaluate the association between apolipoprotein E genotype and postoperative neurodevelopmental dysfunction. Developmental outcomes were evaluated at 1 year of age by using the Bayley Scales of Infant Development. Results: One-year evaluation was performed in 244 patients. After adjustment for preoperative and postoperative covariates-including gestational age, age at operation, sex, race, socioeconomic status, cardiac defect, and use of deep hypothermic circulatory arrest-the apolipoprotein E ε2 allele was associated with a worse neurologic outcome as assessed by the Psychomotor Developmental Index of the Bayley Scales of Infant Development (P = .036). Patients with the apolipoprotein E ε2 allele had approximately a 7-point decrease in the Psychomotor Developmental Index. Conclusions: Apolipoprotein E ε2 allele carriers had significantly lower Psychomotor Development Index scores at 1 year of age after infant cardiac surgery. The effect was independent of ethnicity, socioeconomic status, cardiac defect, and use of deep hypothermic circulatory arrest. An effect of the apolipoprotein E ε4 allele was not detected. Genetic polymorphisms that decrease neuroresiliency and impair neuronal repair after central nervous system injury are important risk factors for neurodevelopmental dysfunction after infant cardiac surgery.

Original languageEnglish
Pages (from-to)1736-1745
Number of pages10
JournalJournal of Thoracic and Cardiovascular Surgery
Volume126
Issue number6
DOIs
StatePublished - Dec 2003

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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