RELAXIN AND IMMUNE FACTORS AS PREDICTORS OF BIOLOGICAL PREPARATION FOR LABOUR

Abstract

Introduction. Biological preparedness for childbirth plays an important role in ensuring the normal course of spontaneous labour, as well as determining the criteria for preinduction and induction of labour with obstetrics pathologies. Recent studies have shown that labour involves a complex interaction between maternal and fetal factors that contribute to cervical maturation and myometrial contraction. In its turn it prompts the search for predictors that allow early identification of pathologies and improve the prognosis. The Relaxin hormone may function as one of the aforementioned predictors due to the emerging evidence for its involvement in the pathogenesis of abortion. Studies show that Relaxin plays a key role in the adaptation of a female 51 body by targeting the cervix among other organs. Relaxin acts on the cervix by degrading extracellular matrix components through activation of proteolytic enzymes, known as matrix metalloproteinases (MMPs). Remodeling of the cervix is a combination of endocrine and immune interactions. One of the hallmarks of cervix remodeling is infiltration of leukocytes prior to labour. These tissue granulocytes become the source of proinflammatory cytokines that upregulate MMPs. Relaxin controls the local inflammatory response by modulating matrix metalloproteinases. Thus, understanding the regulatory role of Relaxin in systemic production of cytokines and its effect on neutrophils at different stages of cervical maturation is of great interest. Aim: characterise the interplay between Relaxin, cytokines and their joint role in regulation of proteolytic enzymes to establish new criteria for prognosis of cervical maturation. Materials and methods. 69 pregnant women of gestational age 38-40 weeks were examined. The examined women were divided into 3 clinical groups, depending on the degree of cervix maturity at the time of hospitalisation. The degree of cervix maturity was assessed by the EH Bishop scale. Group I consisted of 23 patients with a mature cervix (9-13 points), group II included 21 pregnant women with an immature cervix (6-8 points), group III contained 25 pregnant women with a completely immature cervix (0-5 points). The control group consisted of 15 women of gestational age 35-36 weeks, who were pregnant for the first time. Women of the control group were examined prior to the start of physiological processes of remodeling of cervical tissues before labour and displayed no signs of premature labour. Control group was compared to women from the I, II and III groups by disease history and somatic data. All pregnant women underwent standardized clinical examination and immunological testing. Serum concentration of cytokines IL-6 and TNF-α, MMP-1 and MMP-9, and Relaxin levels were determined by enzyme-linked immunosorbent assay using commercial kits. Statistical analysis of the results was performed using the program "STATISTICA-6". Statistical significance was calculated by Student's t-test. Spearman's rank correlation coefficient was determined between the obtained parameters. The differences were considered accurate with a significance level of p<0.05. Results. The average age of the examined pregnant women was 25 years 7 months (18-33). All patients of the examined groups could be compared to each other by their age, genital features and menstrual function (p ≤ 0.05). The study has shown that the lowest serum concentration of Relaxin was found in women with immature or completely immature cervix, which accounted to 189.7±34.6 pg / ml and 208, 9±27.6 pg / ml, respectively. This suggests that serum concentration of Relaxin could serve as a possible predictor of biological readiness of the body for labour. Furthermore, serum Relaxin concentration can serve as a prognostic marker of the effectiveness of induction and preinduction of labour. The data presented shows that women with mature cervix display maximum levels of matrix metalloproteinases MMP9 and MMP-1. Specifically, the concentration was 1.8 times higher than in the group of women with immature cervix. Thus, maturation of the cervix uterus involves a significant increase in the concentration of matrix metalloproteinases by peripheral neutrophils with a gradual increase in their proteolytic activity. Our study showed that high serum concentrations of the proinflammatory cytokines in pregnant women with a mature cervix before labour were higher compared to women with an immature or completely immature cervix. The interplay between proinflammatory cytokines and other modulators presented here during the preparation of the body for labour was evident from the observed correlation. We observed a strong correlation between the level of Relaxin and matrix metalloproteinases (r = 0, 78), as well as positive correlation between their content and the cytokines of interest. Conclusion. The study allowed to identify the most prognostically significant molecular predictors that characterize the body's preparation for labour, which include the "birth hormone" Relaxin. Furthermore, our analysis implicates immune mechanisms in regulating cervical maturation before labour.