Abstract
Introduction: Development of the preterm brain is adversely affected by inflammation. Depending upon the organ, the insult and the temporal relationship between injury and assay cylcooxygenase (COX: prostaglandin H synthase) may have both anti-inflammatory and pro-inflammatory actions. The gene encoding the inducible form of cyclooxygenase, COX-2, is polymorphic for a GC substitution within the promoter region of the gene (at position −765). In vitro the G allele increases COX-2 activity relative to the C allele.
Aim: To determine if the COX-2 -765 GC polymorphism influences neuro-developmental progress after preterm birth.
Patients/Methods: 209 surviving Caucasian preterm infants of median gestation 30 weeks (range 22–32 weeks) had COX-2 genotype determined. Neuro-cognitive outcomes were: any disability and Griffiths Developmental Quotient (DQ) at 2 yrs and General Cognitive ability (GCA) at 5 ½ yrs (British Ability Scales-11).
Results: Genotypes were: GG 139 (66%), GC (32%), CC (1%). When comparing COX-2 G allele (GG+GC) with COX-2 CC genotype, there were no associations with neuro-developmental outcomes. However, COX-2 C allele (GG+GC) was associated with worse DQ and GCA when compared to COX-2 GG genotype. COX-2 C allele (GC+CC) was not associated with disability.
Pearson Chi Square, Mann Whitney U or Student T Test: n (%), median (interquartile range), mean (SE) as appropriate. NS is not significant. There were no differences in family/social variables across genotypes.
Conclusion: The presence of a C allele at position -765 of the COX-2 gene, encoding relatively low COX-2 activity in vitro, is associated with worse neuro-cognitive performance at 2 and 5 ½ years of age in children born at < 33 weeks gestation. The use of COX-2 inhibitors as anti-inflammatory agents in the preterm may be deleterious.
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Harding, D., Montgomery, H., Humphries, S. et al. 104 Does Common Variation In The Cylcooxygenase-2 Gene Affect Neuro-Cognitive Outcome after Premature Birth?. Pediatr Res 56, 481 (2004). https://doi.org/10.1203/00006450-200409000-00127
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DOI: https://doi.org/10.1203/00006450-200409000-00127