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

Gaynor, J. William; Nord, Alexander; Wernovsky, Gil; Bernbaum, Judy; Solot, Cynthia; Burnham, Nancy; Zackai, Elaine H.; Heagerty, Patrick J.; Clancy, Robert R.; Nicolson, Susan C.; Jarvik, Gail P.; Gerdes, Marsha

doi:10.1542/peds.2008-2281

Cited by 87 publications

(87 citation statements)

References 32 publications

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“…A previous study (Gaynor et al. 2009) also did not find a significant effect regarding ADHD specifically. However, this study was conducted using children of preschool age who were much younger than those of this study.…”

Section: Discussionmentioning

confidence: 81%

“…Interestingly, these results in adolescents are opposite to what was found (Gaynor et al. 2009) in CHD patients of preschool age (i.e., the ε2 allele is deleterious while the ε4 allele is neuroprotective).…”

Section: Discussionmentioning

confidence: 99%

“…We previously identified and validated an association of APOE genotype with early neurodevelopmental outcomes after cardiac surgery in neonates and infants with CHD (Gaynor et al. 2003, 2009, 2014). The APOE ε2 allele (described in Materials and Methods) was associated with worse performance at 12–14 months of age after surgery and with an increased risk of behavior problems at 4 years of age, while the APOE ε4 allele was associated with better outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Organizational topology of brain and its relationship to ADHD in adolescents with d‐transposition of the great arteries

et al. 2016

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ObjectiveLittle is currently known about the impact of congenital heart disease (CHD) on the organization of large‐scale brain networks in relation to neurobehavioral outcome. We investigated whether CHD might impact ADHD symptoms via changes in brain structural network topology in a cohort of adolescents with d‐transposition of the great arteries (d‐TGA) repaired with the arterial switch operation in early infancy and referent subjects. We also explored whether these effects might be modified by apolipoprotein E (APOE) genotype, as the APOE ε2 allele has been associated with worse neurodevelopmental outcomes after repair of d‐TGA in infancy.MethodsWe applied graph analysis techniques to diffusion tensor imaging (DTI) data obtained from 47 d‐TGA adolescents and 29 healthy referents to construct measures of structural topology at the global and regional levels. We developed statistical mediation models revealing the respective contributions of d‐TGA, APOE genotype, and structural network topology on ADHD outcome as measured by the Connors ADHD/DSM‐IV Scales (CADS).ResultsChanges in overall network connectivity, integration, and segregation mediated worse ADHD outcomes in d‐TGA patients compared to healthy referents; these changes were predominantly in the left and right intrahemispheric regional subnetworks. Exploratory analysis revealed that network topology also mediated detrimental effects of the APOE ε4 allele but improved neurobehavioral outcomes for the APOE ε2 allele.ConclusionOur results suggest that disruption of organization of large‐scale networks may contribute to neurobehavioral dysfunction in adolescents with CHD and that this effect may interact with APOE genotype.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Organizational topology of brain and its relationship to ADHD in adolescents with d‐transposition of the great arteries

et al. 2016

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“…50 In comparison with normative populations, survivors of infant heart surgery have more problems with reasoning, learning, executive function, inattention and impulsive behavior, language skills, and social skills. [51][52][53] The past decade has heightened awareness of neurocognitive challenges in children with CHD, and American Heart Association recommendations now provide guidance to pediatric caregivers about the need for regular screening for those at high risk. Nucleosome with histone octamer and DNA, with H3K4 methylation bound by CHD7, H3K27 methylation, and H2BK120 ubiquitination is shown.…”

Section: Neurodevelopment In Chdmentioning

confidence: 99%

Trends in Congenital Heart Disease

2016

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“…1 Small studies at individual institutions have shown that children with CHD undergoing surgery in infancy have more problems with reasoning, learning, executive function, inattention and impulsive behavior, language skills, and social skills compared with peers without CHD. [2][3][4][5] Lower abilities in these areas may lead to poor school performance, strained interpersonal relationships, and behavior problems. Survivors of cardiac surgery in infancy are more likely than the general population to require remedial services, including tutoring and special education, as well as physical, occupational, and speech therapy.…”

Section: What This Study Addsmentioning

confidence: 99%

Neurodevelopmental Outcomes After Cardiac Surgery in Infancy

2015

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, for the International Cardiac Collaborative on Neurodevelopment (ICCON) Investigators abstract BACKGROUND: Neurodevelopmental disability is the most common complication for survivors of surgery for congenital heart disease (CHD). METHODS:We analyzed individual participant data from studies of children evaluated with the Bayley Scales of Infant Development, second edition, after cardiac surgery between 1996 and 2009. The primary outcome was Psychomotor Development Index (PDI), and the secondary outcome was Mental Development Index (MDI).RESULTS: Among 1770 subjects from 22 institutions, assessed at age 14.5 6 3.7 months, PDIs and MDIs (77.6 6 18.8 and 88.2 6 16.7, respectively) were lower than normative means (each P , .001). Later calendar year of birth was associated with an increased proportion of high-risk infants (complexity of CHD and prevalence of genetic/extracardiac anomalies). After adjustment for center and type of CHD, later year of birth was not significantly associated with better PDI or MDI. Risk factors for lower PDI were lower birth weight, white race, and presence of a genetic/extracardiac anomaly (all P # .01). After adjustment for these factors, PDIs improved over time (0.39 points/year, 95% confidence interval 0.01 to 0.78; P = .045). Risk factors for lower MDI were lower birth weight, male gender, less maternal education, and presence of a genetic/extracardiac anomaly (all P , .001). After adjustment for these factors, MDIs improved over time (0.38 points/year, 95% confidence interval 0.05 to 0.71; P = .02).CONCLUSIONS: Early neurodevelopmental outcomes for survivors of cardiac surgery in infancy have improved modestly over time, but only after adjustment for innate patient risk factors. As more high-risk CHD infants undergo cardiac surgery and survive, a growing population will require significant societal resources.

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

Cited by 87 publications

References 32 publications

Organizational topology of brain and its relationship to ADHD in adolescents with d‐transposition of the great arteries

Organizational topology of brain and its relationship to ADHD in adolescents with d‐transposition of the great arteries

Trends in Congenital Heart Disease

Neurodevelopmental Outcomes After Cardiac Surgery in Infancy

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