PATHOGENETIC VALIDATION OF ADDITIONAL OBJECTIVE CRITERIA FOR POSSIBLE EFFECTIVE PREGNANCY PROLONGATION AFTER PREMATURE MEMBRANE RUPTURE

The goal of present study was a search for pathogenetical reasoning of an opportunity for prolongation of pregnancy complicated by premature rupture of membranes at a gestational term of 22-34 weeks. The patients were subject to due observation and expectant treatable of pregnancy with prevention of possible infectious and inflammatory complications, as well as monitoring of systemic inflammatory response markers, immune state, and cytokine profile of blood in pregnant women with this disorder. 

We conducted a comprehensive clinical and laboratory examination of fifty pregnant women, whose pregnancy was complicated by premature membrane rupture at 22-34 weeks of gestation. A control group consisted of 40 women with normal pregnancy. For assessment of cellular composition of the blood, a BC3000+ hematological analyzer was used. Distinct subsets of peripheral blood lymphocytes were studied by flow cytometry using monoclonal antibodies («FACS Calibur» «Becton Dickinson», USA). Blood levels of cytokines (IL-2, IL-6, IL-8, TNFα, IL-4, IL-10) were determined by ELISA using test systems (ZAO “VectorBest”, Novosibirsk, Russia). Stereoultrastructural study of membranes was performed with a scanning electron microscope «Hitachi S-450”. 

The findings suggest that the failure of membranes emerging du to systemic metabolic disorders and changes in peripheral blood cells (leukocytosis, lymphopenia due to CD19+ B lymphocytes). Moreover, one could observe reduced counts of CD16+CD56+ T cells (natural killer cells) that showed certain parallelism with increased levels of proinflammatory cytokines (IL-6, IL-8, TNFα) in blood from pregnant PROM, as well as a decrease in IL-10 and IL-4 contents antagonized their proinflammatory effects to certain extent. An opportunity of incomplete pregnancy prolongation for patients with premature rupture of membranes was based on thorough assessment of their somatic and obstetric status and general condition of the fetus, when adequate and comprehensive therapy was applied. In the course of pregnancy prolongation, we found a progressive increase in pro-inflammatory cytokine levels (IL-2, IL-6, IL-8, TNFα), a steady decrease in CD19+ B cell counts, CD3+СD4+ helpers, natural killer cells, increased levels of cytotoxic CD3+CD8+ T cells .The pathogenesis-based criteria for necessary termination of the pregnancy for women with PROM are identified, including an increase in acute-phase proteins levels in blood, development of neutrophilic leukocytosis, lymphopenia, increase of pro-inflammatory cytokine levels in blood (IL-1β, IL-6, IL-8, TNFα), along with progressive reduction of CD3+СD4+ lymphocytes, CD16+CD56+ and CD19+ В lymphocytes. 

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