Biomarkers of inflammation and neoangiogenesis in premature rupture of membranes

BACKGROUND: Premature rupture of membranes complicates up to 2–10% of full-term pregnancies and up to 40% of all premature pregnancies. It is believed that the main cause of premature rupture of membranes is inflammation caused by both infectious agents and autoimmune processes. Numerous studies are aimed at searching for biomarkers that can predict inflammation in premature rupture of membranes. AIM: The aim of this study was to determine the levels of pro-inflammatory cytokines such as interleukin-6, -18 and procalcitonin, as well as interferon-α and soluble endoglin, in the blood serum of pregnant women with premature rupture of membranes and women in labor with timely discharge of amniotic fluid and evaluate the possibility of using these parameters to optimize obstetric tactics. MATERIALS AND METHODS: This study included 69 patients delivered at the Clinic of Obstetrics and Gynecology of the Academician I.P. Pavlov First Saint Petersburg State Medical University from January 2022 to March 2023. The main study group consisted of 53 pregnant women with premature rupture of membranes, the control group included 16 women with term labor and timely discharge of amniotic fluid, or amniotomy performed in the first stage of labor. The levels of interleukin-6, -18, interferon-α, procalcitonin and soluble endoglin in maternal peripheral blood were assessed using enzyme-linked immunosorbent assay. Pregnancies complicated by severe preeclampsia, placenta abruption and chronic maternal diseases in the acute stage were excluded from the study. RESULTS: At the time of rupture, the minimum gestational age was 33+0 weeks and the maximum age — 41+3 weeks. The median duration of the anhydrous interval was 31.8 hours. No significant differences in interleukin-6, -18, procalcitonin and soluble endoglin concentrations were revealed in the main and control groups, interferon-α level being higher in the comparison group. The median concentration of interferon-α in pregnant women with premature rupture of membranes was 1.64 pg/ml and in women with timely discharge of amniotic fluid — 4.61 pg/ml (p = 0.001). A weak direct correlation was revealed between soluble endoglin and interleukin-18 concentrations (R = 0.26; p = 0.03), as well as a moderate direct correlation between soluble endoglin and procalcitonin levels (R = 0.4; p 0.001). CONCLUSIONS: The study did not reveal differences in the concentrations of interleukin-6, -18, procalcitonin and soluble endoglin in the comparison groups. A decrease in interferon-α level in the blood in pregnant women increases the risk of developing premature rupture of membranes. The correlations between soluble endoglin and interleukin-18 or procalcitonin concentrations may indicate an association between different mechanisms of the pathogenesis of premature rupture of membranes. In this regard, an integrated approach and analysis of a combination of several cellular bioregulators are eligible to predict infectious complications in premature rupture of membranes.