Published online June 29, 2009
PEDIATRICS Vol. 124 No. 1 July 2009, pp. 241-250 (doi:10.1542/peds.2008-2281)

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ARTICLE

Apolipoprotein E Genotype Modifies the Risk of Behavior Problems After Infant Cardiac Surgery

J. William Gaynor, MD^a, Alex S. Nord, BA^b, Gil Wernovsky, MD^c,d, Judy Bernbaum, MD^e, Cynthia B. Solot, MA, CCC^f, Nancy Burnham, RN, MSN, CRNP^a, Elaine Zackai, MD^g, Patrick J. Heagerty, PhD^h, Robert R. Clancy, MDⁱ, Susan C. Nicolson, MD^j, Gail P. Jarvik, MD, PhD^b and Marsha Gerdes, PhD^k

^a Divisions of Cardiothoracic Surgery
^c Pediatric Cardiology
^d Critical Medicine
^e General Pediatrics
^g Genetics
ⁱ Neurology
^j Cardiothoracic Anesthesiology
^k Psychology
^f Center for Childhood Communication, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
Departments of^b Medicine (Medical Genetics)
^h Biostatistics, University of Washington, Seattle, Washington

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 2 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 4 allele was associated with a better outcome. APOE 2 carriers had impaired social skills, compared with 4 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 2 allele was associated with increased behavior problems, impaired social interactions, and restricted behavior patterns.

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Key Words: congenital heart defects • genetic predisposition to disease • apolipoprotein E • behavioral symptoms • attention-deficit/hyperactivity disorder • impulsive behavior • autistic disorder

Abbreviations: ADHD—attention-deficit/hyperactivity disorder • CBCL/1.5–5—Child Behavior Checklist for ages 1.5 to 5 years • CHD—congenital heart defect • DHCA—deep hypothermic circulatory arrest • DSM-IV—Diagnostic and Statistical Manual of Mental Disorders; Fourth Edition • NEPSY—Neuro-PSYchology • PKBS—Preschool and Kindergarten Behavior Scale • PLS-4—Preschool Language Scale-4 • TLS—total language score • PDP—pervasive developmental problem • CNS—central nervous system

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Accepted Mar 30, 2009.

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