Abstract
The aim of this study was to analyze the role of the TNF-TNFR system in the materno-fetal unit during both, the normal labor and the labor with risk or signs of infection. The first objective was to analyze TNFR-p55 and p75 expression profiles in the different materno-fetal compartments. The second objective was to determine the plasmatic TNF-a and TNFR levels in newborns with signs of infection and to analyze the usefulness of TNF-a and TNFR as markers of early onset neonatal sepsis and prognostic factors of clinical outcome. Finally, we analyzed the influence of -308 pb TNF-a polymorphism in the idiopatic preterm birth and in preterm premature rupture of the fetal membranes.The results showed that the normal labor represents a physiologic condition characterized by an increase in the soluble TNFR levels and a decrease of TNF-a membrane receptors expression in both maternal peripheral blood and in cord blood in comparison with non-pregnant women. These physiologic changes may provide a protection mechanism conferring a better capacity to buffering the deleterious effects of excessive TNF-a production during gestation. In the context of an intrauterin infection, sTNFR's levels increase in maternal peripheral blood, in cord blood, and in amniotic liquid suggesting a homeostatic function for these soluble receptors attenuating the deleterious effects of excessive TNF-a production associated with the pathologic labor. In the newborns TNF-a and sTNFR's reach the highest levels in presence of clinical and/or biological signs of infection in the first 24 h of life. The simultaneous determination of plasmatic TNF-a and sTNFR's levels is a prognostic factor of clinical outcome. Finally, our results demonstrate an association between TNFA2 allele and preterm premature rupture of the fetal membranes. This association is not independent of HLA-A1, B8, DR3 haplotype. TNFA2 allele and the extended haplotype A1, B8, DR3 may serve as usef
Date of Award | 20 Dec 2002 |
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Original language | Catalan |
Supervisor | Guillem Pintós Morell (Director) |