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 ε2 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 ε4 allele was associated with a better outcome. APOE ε2 carriers had impaired social skills, compared with ε4 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 ε2 allele was associated with increased behavior problems, impaired social interactions, and restricted behavior patterns.

[1]  E. Walker,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[2]  J. Gaynor,et al.  Inattention, Hyperactivity, and School Performance in a Population of School-Age Children With Complex Congenital Heart Disease , 2008, Pediatrics.

[3]  G. Vingerhoets,et al.  Behavior and Self-Perception in Children with a Surgically Corrected Congenital Heart Disease , 2007, Journal of developmental and behavioral pediatrics : JDBP.

[4]  G. Vingerhoets,et al.  Neuropsychological performance in school-aged children with surgically corrected congenital heart disease. , 2007, The Journal of pediatrics.

[5]  G. DuPaul,et al.  Parent and Teacher Ratings of Attention-Deficit/Hyperactivity Disorder in Preschool: The ADHD Rating Scale-IV Preschool Version , 2007 .

[6]  B. Herpertz-Dahlmann,et al.  Attentional dysfunction in children after corrective cardiac surgery in infancy. , 2007, The Annals of thoracic surgery.

[7]  M. Wainwright,et al.  Association of Apolipoprotein E Genotype and Cerebral Palsy in Children , 2007, Pediatrics.

[8]  A. Sands,et al.  Determinants of neuropsychological and behavioural outcomes in early childhood survivors of congenital heart disease , 2006, Archives of Disease in Childhood.

[9]  R. Guerrant,et al.  Role of apolipoprotein E4 in protecting children against early childhood diarrhea outcomes and implications for later development. , 2007, Medical hypotheses.

[10]  B. Herpertz-Dahlmann,et al.  Long-Term Behavior and Quality of Life After Corrective Cardiac Surgery in Infancy for Tetralogy of Fallot or Ventricular Septal Defect , 2007, Pediatric Cardiology.

[11]  M. Poca,et al.  Influence of APOE polymorphism on cognitive and behavioural outcome in moderate and severe traumatic brain injury , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[12]  W. Strittmatter,et al.  Apolipoprotein E and brain injury: implications for children , 2005, Developmental medicine and child neurology.

[13]  D. Wypij,et al.  Prediction of IQ and Achievement at Age 8 Years From Neurodevelopmental Status at Age 1 Year in Children With D-Transposition of the Great Arteries , 2004, Pediatrics.

[14]  E. Zackai,et al.  Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery. , 2003, The Journal of thoracic and cardiovascular surgery.

[15]  Joel Schwartz,et al.  Apolipoprotein E Genotype Predicts 24-Month Bayley Scales Infant Development Score , 2003, Pediatric Research.

[16]  Gil Wernovsky,et al.  Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: the Boston Circulatory Arrest Trial. , 2003, The Journal of thoracic and cardiovascular surgery.

[17]  K. Uzark,et al.  Parenting stress and children with heart disease. , 2003, Journal of pediatric health care : official publication of National Association of Pediatric Nurse Associates & Practitioners.

[18]  B. Herpertz-Dahlmann,et al.  Long term behavioural outcome after neonatal arterial switch operation for transposition of the great arteries , 2002, Archives of disease in childhood.

[19]  J. Newburger,et al.  Influence of Parental Stress and Social Support on the Behavioral Adjustment of Children with Transposition of the Great Arteries , 2002, Journal of developmental and behavioral pediatrics : JDBP.

[20]  이정미,et al.  The Performance of Autistic Children on the Korean Wechsler Preschool and Primary Scale of Intelligence , 2002 .

[21]  T. Achenbach,et al.  The Child Behavior Checklist and related forms for assessing behavioral/emotional problems and competencies. , 2000, Pediatrics in review.

[22]  D. Bichell,et al.  Developmental outcome after surgical versus interventional closure of secundum atrial septal defect in children. , 1999, Circulation.

[23]  D. Wypij,et al.  Developmental and neurological status of children at 4 years of age after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. , 1999, Circulation.

[24]  A. Roses,et al.  Apolipoprotein E and the CNS Response to Injury , 1998, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[25]  A. Roses Apolipoprotein E, a Gene with Complex Biological Interactions in the Aging Brain , 1997, Neurobiology of Disease.

[26]  W. White,et al.  Preliminary report of a genetic basis for cognitive decline after cardiac operations. The Neurologic Outcome Research Group of the Duke Heart Center. , 1997, The Annals of thoracic surgery.

[27]  B. Craig,et al.  Behavioral adjustment of children with surgically palliated complex congenital heart disease. , 1996, Journal of pediatric psychology.

[28]  G. Holmes,et al.  Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary arrest , 1995 .

[29]  J. Simpson,et al.  Parent and teacher perceptions of child behaviour following cardiac surgery , 1994, Acta paediatrica.

[30]  David S. Smith,et al.  A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery. , 1994 .

[31]  A. B. Hollingshead,et al.  Four factor index of social status , 1975 .