Apolipoprotein E genotype modifies the risk of behavior problems after infant cardiac surgery

Abstract

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.

FIGURE 1

APOE genotype effects, after correction for covariates, on the CBCL/1.5–5 narrow-band problem scores, DSM-IV–oriented scores, broad-band indices (internalizing and externalizing problems), and total problem score. Higher scores indicate worse performance. The APOE ε2 and ε4 groups were compared with the reference ε3ε3 group.