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Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery
J William Gaynor1, Marsha Gerdes, Elaine H Zackai
1Division of Cardiothoracic Surgery, The Children's Hospital of Philadelphia, PA 19104, USA. gaynor@email.chop.edu
Insights
Apolipoprotein E epsilon2 allele carriers experienced poorer neurodevelopmental outcomes after infant heart surgery. This genetic factor impacts cognitive development independently of other risk factors.
Area of Science:
- Pediatric Cardiology
- Neurodevelopmental Pediatrics
- Human Genetics
Background:
- Congenital heart defect repair can lead to adverse neurodevelopmental outcomes in children.
- Significant variability exists in developmental outcomes among children with similar cardiac defects.
- Apolipoprotein E (APOE) gene polymorphisms are linked to neurological recovery after central nervous system injury.
Purpose of the Study:
- To investigate the association between apolipoprotein E genotype and neurodevelopmental dysfunction in infants post-cardiac surgery.
- To evaluate the impact of APOE polymorphisms on cognitive outcomes at one year of age.
Main Methods:
- Prospective study of infants (<6 months) undergoing cardiopulmonary bypass for congenital heart defect repair.
- Assessment of neurodevelopmental outcomes at 1 year using the Bayley Scales of Infant Development.
- Analysis of APOE genotype in relation to Psychomotor Developmental Index (PDI) scores.
Main Results:
- The apolipoprotein E epsilon2 allele was significantly associated with worse neurologic outcomes (P=.036).
- Patients with the APOE epsilon2 allele showed an approximate 7-point decrease in the Psychomotor Developmental Index.
- No significant effect of the apolipoprotein E epsilon4 allele on neurodevelopmental outcomes was detected.
Conclusions:
- APOE epsilon2 allele carriers exhibit significantly lower PDI scores at one year post-infant cardiac surgery.
- The observed effect of APOE epsilon2 is independent of ethnicity, socioeconomic status, cardiac defect type, and deep hypothermic circulatory arrest.
- Genetic variations influencing neuroresiliency and neuronal repair are critical risk factors for neurodevelopmental dysfunction following infant cardiac surgery.
Background:
There has been increasing recognition of adverse neurodevelopmental sequelae in some children after repair of congenital heart defects. Even among children with the same cardiac defect, significant interindividual variation exists in developmental outcome. Polymorphisms of apolipoprotein E have been identified as a risk factor for worse neurologic recovery after central nervous system injury.
Methods:
A single-institution prospective study of patients
Results:
One-year evaluation was performed in 244 patients. After adjustment for preoperative and postoperative covariates-including gestational age, age at operation, sex, race, socioeconomic status, cardiac defect, and use of deep hypothermic circulatory arrest-the apolipoprotein E epsilon2 allele was associated with a worse neurologic outcome as assessed by the Psychomotor Developmental Index of the Bayley Scales of Infant Development (P =.036). Patients with the apolipoprotein E epsilon2 allele had approximately a 7-point decrease in the Psychomotor Developmental Index.
Conclusions:
Apolipoprotein E epsilon2 allele carriers had significantly lower Psychomotor Development Index scores at 1 year of age after infant cardiac surgery. The effect was independent of ethnicity, socioeconomic status, cardiac defect, and use of deep hypothermic circulatory arrest. An effect of the apolipoprotein E epsilon4 allele was not detected. Genetic polymorphisms that decrease neuroresiliency and impair neuronal repair after central nervous system injury are important risk factors for neurodevelopmental dysfunction after infant cardiac surgery.
