Cognitive outcome and cyclo-oxygenase-2 gene (-765 G/C) variation in the preterm infant.
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.


RESULTS
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 5(1/2) 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 5(1/2) 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.


CONCLUSIONS
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.
Harding
D R
DR
Neonatal Intensive Care Unit, University of Bristol, D level, St Michael's Hospital, Bristol BS2 8EG, UK. david.harding@bristol.ac.uk
Humphries
S E
SE
Whitelaw
A
A
Marlow
N
N
Montgomery
H E
HE
D000483:Alleles; D001724:Birth Weight; D002547:Cerebral Palsy / Q000235:genetics; D002657:Child Development; D003071:Cognition; D051546:Cyclooxygenase 2 / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000523:psychology*; D008297:Male; D009048:Motor Skills; D011110:Polymorphism, Genetic; D011379:Prognosis
D051546:Cyclooxygenase 2