Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery.
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 <or=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 epsilon2 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 epsilon2 allele had approximately a 7-point decrease in the Psychomotor Developmental Index.


CONCLUSIONS
Apolipoprotein E epsilon2 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 epsilon4 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.
Gaynor
J William
JW
Division of Cardiothoracic Surgery, The Children's Hospital of Philadelphia, PA 19104, USA. gaynor@email.chop.edu
Gerdes
Marsha
M
Zackai
Elaine H
EH
Bernbaum
Judy
J
Wernovsky
Gil
G
Clancy
Robert R
RR
Newman
Mark F
MF
Saunders
Ann M
AM
Heagerty
Patrick J
PJ
D'Agostino
Jo Ann
JA
McDonald-McGinn
Donna
D
Nicolson
Susan C
SC
Spray
Thomas L
TL
Jarvik
Gail P
GP
D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D002508:Cephalometry; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000209:etiology* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006330:Heart Defects, Congenital / Q000235:genetics / Q000601:surgery*; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D011379:Prognosis; D011446:Prospective Studies
D001057:Apolipoproteins E