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Session H: Developmental Pediatrics

Background: The Apolipoprotein E (APO E) 4 allele is associated with poor outcome after brain injury in adults but may be protective in very young children. Cerebral palsy (CP) is a subset of brain injury secondary to a neurological insult in the developing brain. Objective: To investigate the relationship between the APO E 4 allele and severity of motor impairment in CP. Design: A cross-sectional study of APO E genotypes and gross motor function classification among individuals with CP. Participants: One hundred and seventy-nine individuals with CP at the University of Virginia or its satellite clinic; mean age was 9 years 1 month; 56% were males. Method: Genomic DNA was extracted from buccal swabs for APO E genotyping by Taqman fluorescent resonance energy transfer assays on each participant. Functional motor severity was assessed using the Gross Motor Function Classification System (GMFCS), grouped as Levels I and II (less severe group) and Levels III to V (more severe or nonindependent ambulators). A χ2 analysis was performed to assess the association between the presence of the APO E 4 allele and severity. Results: Thirty percent of participants had at least one APO E 4 allele. A significantly higher proportion of participants with an APO E 4 allele were in the low severity group (p<0.05). In addition, while 61% of the patients with one APO E 4 allele were considered less severe, 80% of the group with two APO E 4 alleles were classified as less severe. An APO E 4 allele appeared to have the greatest protective effect for brain injury occurring in the perinatal period (p<0.05) and with gestational age >36 weeks (p<0.05). Conclusions: In contrast to adults, the APO E 4 allele appears to confer protection and/or facilitate recovery after brain injury in the fetus or newborn. This finding has important implications for future clinical trials that mimic the salutary effects of APO E. It is important to know whether the APO E 4 isoform is helpful or harmful in the immature brain.