Genetic factors are important determinants of neurodevelopmental outcome after repair of tetralogy of Fallot

Objective: Adverse neurodevelopmental sequelae are common in children with congenital heart defects. Tetralogy of Fallot is part of the clinical phenotype of many genetic syndromes. We evaluated the determinants of neurodevelopmental outcome in patients with tetralogy of Fallot. Methods: We performed a subgroup analysis of children with tetralogy of Fallot undergoing complete repair before 6 months of age who were enrolled in a trial assessing apolipoprotein E genotype as a predictor of neurodevelopmental outcome. Assessment included genetic evaluation, neurologic examination, and the Bayley Scales of Infant Development-II, yielding the Mental Developmental Index and Psychomotor Developmental Index. Results: Sixty children were tested at 1 year of age. A confirmed or suspected genetic syndrome was identified in 18.3%. The mean Mental Developmental Index was 89 ± 13, and the mean Psychomotor Developmental Index was 81 ± 17. Scores for the Mental Developmental Index (76 ± 13 vs 92 ± 11) and Psychomotor Developmental Index (63 ± 13 vs 85 ± 15) were significantly lower for patients with genetic syndromes. The presence of a genetic syndrome was a predictor of lower Mental Developmental Index and Psychomotor Developmental Index (P = .002 and P = .001). The presence of tetralogy of Fallot with pulmonary atresia and the apolipoprotein E ε2 allele were predictive of a lower Mental Developmental Index (P = .001 and P = .035). No other preoperative or operative variables were predictive of worse neurodevelopmental outcome. Conclusions: At 1 year of age after repair of tetralogy of Fallot, most patients had neurodevelopmental scores within the normal range. Genetic syndromes and the apolipoprotein E ε2 allele were important risk factors for neurodevelopmental dysfunction and accounted for some interindividual differences in outcome.