Apolipoprotein E genotype modifies the risk of behavior problems after infant cardiac surgery.
OBJECTIVE
The goal was to evaluate polymorphisms of the APOE gene as modifiers of neurobehavioral outcomes for preschool-aged children with congenital heart defects, after cardiac surgery.


METHODS
A prospective observational study with neurodevelopmental evaluation between the fourth and fifth birthdays was performed. Attention and behavioral skills were assessed through parental report.


RESULTS
Parents of 380 children completed the neurobehavioral measures. Child Behavior Checklist scores for the pervasive developmental problem scale were in the at-risk or clinically significant range for 15% of the cohort, compared with 9% for the normative data (P < .00001). Attention problem scores were in the at-risk or clinically significant range for 12% of the cohort, compared with 7% for the normative data (P = .0002). The Attention-Deficit/Hyperactivity Disorder Rating Scale-IV, Preschool Version, was completed for 378 children; 30% scored in the clinically significant range for inattention and 22% for impulsivity. After adjustment for covariates, the APOE epsilon2 allele was significantly associated with higher scores (worse problems) for multiple Child Behavior Checklist indices, including somatic complaints (P = .009), pervasive developmental problems (P = .032), and internalizing problems (P = .009). In each case, the epsilon4 allele was associated with a better outcome. APOE epsilon2 carriers had impaired social skills, compared with epsilon4 carriers (P = .009).


CONCLUSIONS
For preschool-aged children with congenital heart defects requiring surgery, parental rating scales showed an increased prevalence of restricted behavior patterns, inattention, and impaired social interactions. The APOE epsilon2 allele was associated with increased behavior problems, impaired social interactions, and restricted behavior patterns.
Gaynor
J William
JW
Division of Cardiothoracic Surgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. gaynor@email.chop.edu
Nord
Alex S
AS
Wernovsky
Gil
G
Bernbaum
Judy
J
Solot
Cynthia B
CB
Burnham
Nancy
N
Zackai
Elaine
E
Heagerty
Patrick J
PJ
Clancy
Robert R
RR
Nicolson
Susan C
SC
Jarvik
Gail P
GP
Gerdes
Marsha
M
D001057:Apolipoproteins E / Q000235:genetics*; D001288:Attention / Q000502:physiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D002653:Child Behavior Disorders / Q000453:epidemiology* / Q000235:genetics*; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006330:Heart Defects, Congenital / Q000601:surgery*; D006801:Humans; D007175:Impulsive Behavior / Q000235:genetics; D007398:Interpersonal Relations; D008297:Male; D011184:Postoperative Period; D015995:Prevalence; D011446:Prospective Studies; D011795:Surveys and Questionnaires
D001057:Apolipoproteins E