Biomarcadores predictores de preeclampsia y efectividad del tratamiento con aspirina en gestantes de alto riego

Zusammenfassung

OBJECTIVES: Predicting preeclampsia is a major challenge in contemporary obstetrics. Many of the associated changes in the pathogenesis of preeclampsia precede the establishment of clinical disease. That's why the search for markers that reflect this variation in the placental environment and in the maternal circulation can lead to the implementation of a screening program in pregnant women for the detection of those that present high risk and to establish on them an adequate follow-up and the taking of opportune preventive measures. Today screening tools are based on a set of clinical markers, ultrasound and biomarkers in serum but its implementation is only possible in specialized centers. Serum biomarkers have great advantages over the use of other types of predictor variables. On the one hand, they are non-invasive, reproducible tests that show changes in early stages of PE, in many cases prior to alterations detected with other techniques, which allows an earlier detection of the disease. All these reasons make biomarkers ideal candidates for the prediction and diagnosis of preeclampsia. Therefore, in this study we focused on evaluating the clinical utility of biomarkers in serum individually and combined by designing predictive algorithms in the three trimesters of pregnancy in order to achieve an effective screening method applicable to general practice. Likewise, the evolution of these biomarkers throughout pregnancy is evaluated and their evolution is compared in women treated with aspirin vs placebo, at the same time as the efficacy of this drug is determined as preventive treatment of preeclampsia. METHODOLOGY: The present doctoral thesis is a descriptive and analytical prospective study made on the basis of a clinical trial carried out in the Hospital Universitario Virgen de la Arrixaca of Murcia, which has been developed within the framework of a multicenter research project. 'Combined multi-marker screening and randomized patient treatment with aspirin for evidence based pre-eclampsia prevention. ASPRE ''. We included 119 patients at high risk of preeclampsia who agreed to participate in the clinical trial in the period from September 2015 to October 2016. Each participant was assigned a random number, which determined whether they received placebo or Aspirin 150 mg. Subsequently, the data collection, the processing of the samples, the analytical determinations and the analysis of the results were carried out. CONCLUSIONS: The studies carried out in this Doctoral Thesis have led us to the following conclusions: - An early screening strategy for PE has been developed on pregnant women at high risk a priori through the combination of interleukin-6 and Lipoprotein (a), which, applied at the end of the first trimester, manages to detect 100% of the cases of Preterm PE with a specificity of 83.3% and 91.6% in all cases of PE with a specificity of 97.2%. - The model of risk prediction in the second and third trimesters of pregnancy led us to a model that used AST as a biochemical marker and BMI as a maternal variable, which showed moderate efficacy in the 3rd trimester but poor in the 2nd trimester of gestation. - Significant differences were observed in the group treated with aspirin with respect to the one treated with placebo in the concentrations of triglycerides, IL-6 and glucose in the second trimester and of sFlt-1 in the third trimester of pregnancy, which could explain part of the mechanism of action of aspirin in the prevention of preeclampsia.