OBJECTIVE: The severity of the proinflammatory response may determine outcome in the critically ill. Genetic variation in the promoter region of the gene encoding the proinflammatory cytokine interleukin-6 (IL-6; -174 CC genotype) may encode enhanced production of IL-6. Our objective was to determine whether the CC genotype is associated with worse early illness severity, neurologic injury, and lower developmental scores among surviving preterm children. METHODS: Genotype was determined from dried blood spots that were taken for neonatal screening tests 7 days or more after birth; outcome was independently assessed as part of a longitudinal study of children of < or =32 weeks' gestational age. RESULTS: CC genotype was associated with worse intensive care indices. Significant hemorrhagic brain injuries occurred in 5 (19\%) of 27 children with CC genotype compared with 7 (6\%) of 121 children with GC or GG genotype, and images consistent with white matter damage (ventriculomegaly or cystic periventricular leukomalacia) occurred in 9 (26\%) of CC patients compared with 9 (7\%) in GC/GG children. Disability occurred significantly more often in CC children: 8 (31\%) compared with 16 (13\%). A similar trend was also noted in children with cerebral palsy (15\% compared with 7\%, respectively). Developmental, cognitive, and motor scores at 2 years and 5.5 years were independent of genotype among children with or without disability. CONCLUSIONS: In a population of surviving children who were born at < or =32 weeks' gestational age, variation of the gene that may increase IL-6 synthesis is associated with disabling brain injury but not cognitive development despite association with worse early critical care indices.
%0 Journal Article
%1 Harding2004
%A Harding, David R
%A Dhamrait, Sukbhir
%A Whitelaw, Andrew
%A Humphries, Steve E
%A Marlow, Neil
%A Montgomery, Hugh E
%D 2004
%J Pediatrics
%K Cerebral Hemorrhage; Palsy; Developmental Disabilities; Female; Genotype; Humans; Infant, Newborn; Premature; Premature, Diseases; Interleukin-6; Leukomalacia, Periventricular; Male; Severity of Illness Index
%N 4
%P 941--947
%R 10.1542/peds.2003-0494-F
%T Does interleukin-6 genotype influence cerebral injury or developmental progress after preterm birth?
%U http://dx.doi.org/10.1542/peds.2003-0494-F
%V 114
%X OBJECTIVE: The severity of the proinflammatory response may determine outcome in the critically ill. Genetic variation in the promoter region of the gene encoding the proinflammatory cytokine interleukin-6 (IL-6; -174 CC genotype) may encode enhanced production of IL-6. Our objective was to determine whether the CC genotype is associated with worse early illness severity, neurologic injury, and lower developmental scores among surviving preterm children. METHODS: Genotype was determined from dried blood spots that were taken for neonatal screening tests 7 days or more after birth; outcome was independently assessed as part of a longitudinal study of children of < or =32 weeks' gestational age. RESULTS: CC genotype was associated with worse intensive care indices. Significant hemorrhagic brain injuries occurred in 5 (19\%) of 27 children with CC genotype compared with 7 (6\%) of 121 children with GC or GG genotype, and images consistent with white matter damage (ventriculomegaly or cystic periventricular leukomalacia) occurred in 9 (26\%) of CC patients compared with 9 (7\%) in GC/GG children. Disability occurred significantly more often in CC children: 8 (31\%) compared with 16 (13\%). A similar trend was also noted in children with cerebral palsy (15\% compared with 7\%, respectively). Developmental, cognitive, and motor scores at 2 years and 5.5 years were independent of genotype among children with or without disability. CONCLUSIONS: In a population of surviving children who were born at < or =32 weeks' gestational age, variation of the gene that may increase IL-6 synthesis is associated with disabling brain injury but not cognitive development despite association with worse early critical care indices.
@article{Harding2004,
abstract = {OBJECTIVE: The severity of the proinflammatory response may determine outcome in the critically ill. Genetic variation in the promoter region of the gene encoding the proinflammatory cytokine interleukin-6 (IL-6; -174 CC genotype) may encode enhanced production of IL-6. Our objective was to determine whether the CC genotype is associated with worse early illness severity, neurologic injury, and lower developmental scores among surviving preterm children. METHODS: Genotype was determined from dried blood spots that were taken for neonatal screening tests 7 days or more after birth; outcome was independently assessed as part of a longitudinal study of children of < or =32 weeks' gestational age. RESULTS: CC genotype was associated with worse intensive care indices. Significant hemorrhagic brain injuries occurred in 5 (19\%) of 27 children with CC genotype compared with 7 (6\%) of 121 children with GC or GG genotype, and images consistent with white matter damage (ventriculomegaly or cystic periventricular leukomalacia) occurred in 9 (26\%) of CC patients compared with 9 (7\%) in GC/GG children. Disability occurred significantly more often in CC children: 8 (31\%) compared with 16 (13\%). A similar trend was also noted in children with cerebral palsy (15\% compared with 7\%, respectively). Developmental, cognitive, and motor scores at 2 years and 5.5 years were independent of genotype among children with or without disability. CONCLUSIONS: In a population of surviving children who were born at < or =32 weeks' gestational age, variation of the gene that may increase IL-6 synthesis is associated with disabling brain injury but not cognitive development despite association with worse early critical care indices.},
added-at = {2014-07-19T20:23:27.000+0200},
author = {Harding, David R and Dhamrait, Sukbhir and Whitelaw, Andrew and Humphries, Steve E and Marlow, Neil and Montgomery, Hugh E},
biburl = {https://www.bibsonomy.org/bibtex/2bdeaf200e3df63e64f6f10a6c4e82aff/ar0berts},
doi = {10.1542/peds.2003-0494-F},
groups = {public},
interhash = {e85951bfad4669a4b3f42081b8b71c5f},
intrahash = {bdeaf200e3df63e64f6f10a6c4e82aff},
journal = {Pediatrics},
keywords = {Cerebral Hemorrhage; Palsy; Developmental Disabilities; Female; Genotype; Humans; Infant, Newborn; Premature; Premature, Diseases; Interleukin-6; Leukomalacia, Periventricular; Male; Severity of Illness Index},
month = Oct,
number = 4,
pages = {941--947},
pii = {114/4/941},
pmid = {15466088},
timestamp = {2014-07-19T20:23:27.000+0200},
title = {Does interleukin-6 genotype influence cerebral injury or developmental progress after preterm birth?},
url = {http://dx.doi.org/10.1542/peds.2003-0494-F},
username = {ar0berts},
volume = 114,
year = 2004
}