Djukic, M.Gibson, C.MacLennan, A.Goldwater, P.Haan, E.McMichael, G.Priest, K.Dekker, G.Hague, W.Chan, A.Rudzki, Z.van Essen, P.Khong, T.Morton, M.Ranieri, E.Scott, H.Tapp, H.Casey, G.2009-10-192009-10-192009Australian and New Zealand Journal of Obstetrics and Gynaecology, 2009; 49(3):247-2530004-86661479-828Xhttp://hdl.handle.net/2440/51203Journal compilation © 2009 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Copyright © 2009 John Wiley & Sons, Inc.Aim: Cytokine polymorphisms may alter the fetal inflammatory response, increasing susceptibility to cerebral palsy (CP). This study investigates associations between selected inflammatory mediator and cytokine gene polymorphisms (Toll-like receptor-4 (TLR-4) Asp299Gly, interleukin-6 G-174C and interleukin-4 C-589T) and CP from 443 CP infants and 883 control infants. Results were correlated with viral nucleic acids in the same samples. Results: At all gestational ages (GA), TLR-4 was associated with a decreased risk of developing CP (homozygous/heterozygous odds ratio (OR) 0.70, 95% confidence interval (CI) 0.50–0.98) and interleukin (IL)-6 was associated with an increased risk of developing hemiplegia (OR 1.38, 95% CI 1.05–1.83). For infants born 32–36 weeks GA, there was a tenfold increase in the risk of quadriplegic CP with homozygous/heterozygous IL-6 (OR 10.42, 95% CI 1.34–80.82). Viral exposure in combination with IL-4 in preterm infants was associated with a fourfold increased risk of quadriplegia (homozygous/heterozygous OR 4.25, 95% CI 1.21–14.95). In very preterm infants, the absence of detectable viral exposure in combination with IL-4 decreased the risk of developing CP (homozygous/heterozygous OR 0.31, 95% CI 0.13–0.76). Conclusion: Polymorphisms in TLR-4 may be associated with a decreased risk of CP. Polymorphisms in IL-6 or IL-4 may act as susceptibility genes, in the presence of viral exposure, for the development of hemiplegic and quadriplegic CP. These associations require confirmation but they suggest a hypothesis for CP causation due to double jeopardy from neurotropic viral exposure and genetic susceptibility to infection.encerebral palsyinterleukin-4interleukin-6Toll-like receptor 4Journal article002009091010.1111/j.1479-828X.2009.00999.x0002670678000032-s2.0-7034976221738718Goldwater, P. [0000-0003-4822-8488]Haan, E. [0000-0002-7310-5124]McMichael, G. [0000-0002-6811-5301]Dekker, G. [0000-0002-7362-6683]Hague, W. [0000-0002-5355-2955]Khong, T. [0000-0002-2404-007X]