Abstract
Objective: In a newborn mouse model of brain damage induced by infusion of lipopolysaccharide and subthreshold hypoxic ischemic insult, animals bearing a loss of function mutation of the TLR4-gene were protected against the severe axonal and neuronal loss observed in wild-type animals (PNAS 100:8514–9). We speculate that intrauterine infection and polymorphisms of the innate immune system, like the CD14–159T-, the TLR4–896G and the NOD2–3020insC-polymorphism, might influence the occurence of brain lesions in preterm infants.
Methods: Genotyping of 1262 VLBW-infants (841 enrolled during previous trials, 421 enrolled between September 2003 and November 2004 in our current trial) by PCR and restriction enzyme digestion.
Results: Genotyping was successful in 1243 infants. The CD14–159C/T-polymorphism was associated with the development of IVH. Number of infants (% infants with IVH) according to genotype and intrauterine infection as the cause of preterm birth: CC no infection: 252 (11.9); CC infection: 70 (14.3); CT no infection: 510 (14.9); CT infection 152 (21.7); TT no infection: 190 (21.1); TT infection 69 (29.0). We compared infants with CC-genotype and CT genotype without infection to infants with TT-genotype and CT-genotype with intrauterine infection as the cause of preterm birth in our previous trials and found a significant difference (p=0.003 Fisher's exact test). We were able to confirm these data in our current trial (p=0.03, total p=0.0002, Fisher's exact test). In a multivariate logistic regression analysis including gestational age, the reason of preterm delivery and the CD14-genotype as independent and IVH as dependent variables, only the CD14 genotype (OR 1.39, 95%CI 1.1–1.7, p=0.004) and gestational age (OR 1.31, 95%CI 1.2–1.4, p<0.001) were significant predictors of IVH.
Conclusion: The CD14–159T-allele is associated with an increased rate of IVH in preterm infants.
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Göpel, W., Härtel, C., Kattner, E. et al. 152 Intraventricular Haemorrhage in Very Low Birth Weight Infants: Genotype - Environment Interactions. Pediatr Res 58, 380 (2005). https://doi.org/10.1203/00006450-200508000-00181
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DOI: https://doi.org/10.1203/00006450-200508000-00181