RT Journal Article
SR Electronic
T1 Cognitive outcome and cyclo-oxygenase-2 gene (−765 G/C) variation in the preterm infant
JF Archives of Disease in Childhood - Fetal and Neonatal Edition
JO Arch Dis Child Fetal Neonatal Ed
FD BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health
SP F108
OP F112
DO 10.1136/adc.2006.099499
VO 92
IS 2
A1 D R Harding
A1 S E Humphries
A1 A Whitelaw
A1 N Marlow
A1 H E Montgomery
YR 2007
UL http://fn.bmj.com/content/92/2/F108.abstract
AB Background: Cyclo-oxygenase (COX) inhibition by indomethacin does not result in an improvement in long-term neurocognitive outcome, despite reducing the incidence of both severe intraventricular haemorrhage and white matter injury visible on ultrasound. Diffuse brain injury after preterm birth may have inflammatory origins. These two points suggest that, in the preterm brain, COX inhibition may have a dominant proinflammatory or neuropathological role. The inducible form of the COX2 gene is polymorphic: the −765 C (rather than G) variant of the gene is associated with reduced COX2 activity. Objective: To test the hypothesis that the C allele of COX2 is associated with worse neurodevelopmental outcomes after premature birth. Outcomes: Cerebral palsy, disability, Griffith’s developmental quotient at 2 years and British Ability Scales-11 general cognitive ability and motor performance (movement assessment battery for children) at 5½ years were compared with COX2 genotype. Results: The C allele (GC 65 (31%), CC 3 (1%)) was independently associated with worse cognitive performance at 2 and 5½ years: C allele mean (SEM) developmental quotient 92.7 (1.7), v GG 97.6 (1.5), p = 0.039; C allele mean (SEM) general cognitive ability, 94.3 (2.2) v GG 100.9 (1.7), p = 0.028. Conclusion: An antineuropathological role for COX2 in the preterm brain may help account for the lack of effect of indomethacin treatment in improving neurocognitive outcomes in children born preterm, despite reported reduction in apparent brain injury.