University dissertation from Dept of Obstetrics and Gynecology, Lund, Sweden

Abstract: The aim of the research presented in this thesis was to provide extended background knowledge concerning several biochemical markers, used for the medical evaluation of pregnant women with suspected or confirmed preeclampsia, in order to improve the reliability of monitoring. Plasma levels of beta-2 microglobulin, cystatin C and beta trace protein are known to reflect renal filtration in non-pregnant settings, and the plasma proteins, C-reactive protein and serum amyloid A protein, are known to be sensitive markers of inflammation. Despite pregnancy-related renal hyperfiltration, the plasma levels of beta-2 microglobulin, cystatin C and beta trace protein remained virtually unchanged in the first and second trimesters, with an elevation (20-40%) in the third trimester in a cross-sectional study including 398 women with uncomplicated pregnancies. In a case-control study including 57 women diagnosed with preeclampsia and 218 women with uncomplicated pregnancies, the protein levels were elevated further in women with preeclampsia, and the three plasma proteins had similar diagnostic capacities for the diagnosis of preeclampsia. The placental expression of cystatin C, a strong extracellular protease inhibitor, was up-regulated in the preeclamptic placenta at the mRNA and protein level in a study including placental tissue samples from 13 normal and 22 preeclamptic pregnancies. Real-time polymerase chain reaction (RT-PCR) and in situ hybridization were used for the mRNA expression analysis and immuno-histochemistry and Western blotting were used for the protein expression analysis. In a cross-sectional study including 27 healthy women undergoing planned Caesarean section at term, the concentrations of beta-2 microglobulin, cystatin C and beta trace protein in the uterine vein and the antecubital vein were analysed. No significant concentration gradients were detected, indicating that utero-placental synthesis is not a major source of these proteins in the maternal circulation. The acute-phase proteins, C-reactive protein and serum amyloid A protein were not increased in women with preeclampsia compared with women with normal pregnancy in a study of 299 healthy normotensive women with uncomplicated pregnancies and 57 women with preeclampsia. The acute-phase proteins therefore did not reflect the suggested inflammatory response to preeclampsia. The plasma levels of beta-2 microglobulin, cystatin C and beta trace protein are potential markers of preeclampsia and for the monitoring of renal deterioration as the condition progresses. The proteins could be useful in optimizing the monitoring and timing of delivery of women with preeclampsia.

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