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Vol 70, No 1 (2021)

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Original Research

Cytokine profile in women with threatened miscarriage and intestinal dysbiosis

Bezmenko A.A., Sadovaya N.D., Meshkova M.E., Malakhova E.A.

Abstract

HYPOTHESIS/AIMS OF STUDY: Systemic endotoxinemia resulting from intestinal dysbiosis activates the Th1 immune response and excessive production of proinflammatory cytokines, which can cause abortion. This study was aimed at assessing interleukin levels in women with the threat of miscarriage and exploring their dependence on intestinal microbiocenosis and the level of endotoxinemia.

STUDY DESIGN, MATERIALS AND METHODS: The study involved 87 women aged 18 to 43 years in pregnancy from six to 22 weeks. The main group consisted of 50 women with a threatened miscarriage. The control group included 37 women with normal pregnancy. A qualitative and quantitative analysis of intestinal microbiocenosis was performed by real-time PCR, with endotoxin and interleukin levels evaluated using conventional methods.

RESULTS: In patients of the main group, intestinal dysbiosis of grade I was detected in 30 % (n = 15), of grade II in 46 % (n = 23), and of grade III in 24 % (n = 12) of cases. In the control group, intestinal microflora disorders corresponded to grade I dysbiosis in 67.6 % (n = 25) and grade II dysbiosis in 32.4 % (n = 12) of cases, there being no cases of severe dysbiosis revealed. The level of endotoxin in pregnant women of the main group was 0.57 ± 0.02 nmol / ml and was classified as “increased”. The endotoxin level in the blood serum of pregnant women of the control group was 0.34 ± 0.02 nmol / ml and was characterized as “low” (p < 0.001). A strong correlation was found (r = 0.8, p < 0.001) between the grade of intestinal dysbiosis and the level of endotoxinemia. The cytokine profile in patients of the main group was characterized by increased concentrations of pro-inflammatory cytokines (IL-1β — 4.9 ± 1.6 pg / ml, IL-6 — 4.8 ± 1.5 pg / ml) and a decreased concentration of anti-inflammatory cytokine (IL-10 — 18.0 ± 4.5 pg / ml), when compared to the control group (IL-1β — 1.8 ± 0.2 pg / ml, IL-6 — 2.1 ± 0.2 pg / ml, IL-10 — 30.3 ± 4.4 pg/ml). There were a statistically significant moderate positive correlation between the level of endotoxinemia and the concentration of pro-inflammatory cytokines and a weak negative correlation between the endotoxin level and the concentration of anti-inflammatory IL-10.

CONCLUSION: Endotoxinemia, which occurs as a result of intestinal microflora dysbiosis and activates pro-inflammatory pathways, can really be as a triggering factor in the pathogenesis of miscarriage in pregnant women.

Journal of obstetrics and women's diseases. 2021;70(1):51-58
pages 51-58 views

Placental inflammatory changes and their association with the vaginal microbiota before delivery

Dadayeva D.G., Sosnina A.K., Tral T.G., Tolibova G.K., Budilovskaya O.V., Krysanova A.A., Savicheva A.M., Kogan I.Y.

Abstract

HYPOTHESIS/AIMS OF STUDY: Infection of the amniotic cavity and placenta is one of the leading causes of adverse pregnancy outcomes. In the majority of cases, intra-amniotic infection is associated with the normal microbiota of the lower urogenital tract. The aim of the study was to explore the relationships between the placental inflammatory changes, vaginal microbiota and labor course.

STUDY DESIGN, MATERIALS AND METHODS: We examined 124 women at 37-41 weeks of gestation. The vaginal discharge at admission was taken for microbiological evaluation, with the delivered placenta sent for histological examination.

RESULTS: In 17.7% of cases, histological examination of the placenta revealed inflammatory changes. A statistically significant correlation was noted between the placental inflammatory changes and Staphylocossus spp. presence in the vaginal discharge at admission (р = 0.0004). The placental inflammatory changes were associated with the membrane rupture to delivery interval more than 6 hours (р = 0.01) and the labor duration more than 7 hours (р = 0.0004). Prelabor rupture of membranes did not significantly affect the placental inflammatory changes (p = 1.0).

CONCLUSION: Predisposing factors for the development of ascending bacterial infection of the placenta are an abnormal vaginal microbiota with the presence of opportunistic bacteria before delivery, a long membrane rupture to delivery interval, and a prolonged labor.

Journal of obstetrics and women's diseases. 2021;70(1):59-68
pages 59-68 views

Serotonin and cyclic sleep organization in healthy full-term newborns

Zvereva N.A., Milyutina Y.P., Evsyukova I.I.

Abstract

RELEVANCE: The growth of neuropsychiatric diseases caused by perinatal pathology indicates the need to study the biochemical markers of brain damage in the newborn for the timely prevention of adverse consequences. Serotonin in early ontogenesis provides intensive development of neuronal structures and cortical networks involved in the mechanisms of formation of cyclic sleep organization — a fine criterion of morphofunctional development of the brain.

AIM: The aim of the work is to study the content of serotonin in healthy full-term newborns in comparison with the quantitative and qualitative characteristics of the electropoligraphic sleep pattern.

MATERIAL AND METHODS: 84 healthy newborns were examined, which, depending on the gestational age, were divided into 3 groups: I — 37 weeks (20 people), II — 38 weeks (24 people), III — 39-40 weeks (40 people). The content of serotonin in platelet-rich plasma of blood from the umbilical cord vein and in platelet suspension prepared from venous blood taken from mothers and children on the first day of life and again on day 5 was determined by high-performance liquid chromatography with electrochemical detection. A quantitative and qualitative analysis of the sleep electropoligram was performed 7-12 hours after birth.

RESULTS: The content of serotonin in platelet-rich plasma in umbilical cord blood in children does not depend on the method of birth, is 2 times lower than in the venous blood of mothers (0.379 ± 0.116 microns/l, versus 0.756 ± 0.200 microns/l, but there is a high correlation between the indicators (r = 0.8, p < 0.05). At the gestational age of 39-40 weeks, the level of serotonin in platelet-rich plasma and in venous blood platelets is significantly higher than in those born at 37 weeks. In the latter, the increase in the content of serotonin in platelets continues after birth (at day 1, 0.539 ± 0.149 nM/109 Tr, and on day 5 — 0.846 ± 0.094 nM/109 Tr; p < 0.05), whereas the indicators for those born at 39-40 weeks of pregnancy. They do not change (0.797 ± 0.190 nM/109 Tr and 0.749 ± 0.142 nM/109 Tr, respectively). A significant increase in the content of serotonin in the platelet-rich plasma and in the platelets of the child in the period from 37 to 39 weeks, both during intrauterine development and in the first days of life, correlates with an increase in the representation of the orthodox phase in the sleep cycle.

CONCLUSION: The general pattern of changes in serotonin content and cyclic sleep organization in the early neonatal period in healthy newborns, depending on gestational age, indicates the possibility of using the obtained standard values of serotonin as a biochemical marker of functional brain development.

Journal of obstetrics and women's diseases. 2021;70(1):69-76
pages 69-76 views

Uterotonic drugs in obstetric bleeding prevention and treatment

Ziganshin A.M., Bektasheva I.I., Mudrov V.A.

Abstract

One of the main causes of maternal mortality is obstetric bleeding, among which 2/3 of cases are bleeding in the early postpartum period. The existing methods of preventing and stopping uterine bleeding in the postpartum period do not always allow achieving the desired result due to the ineffectiveness of the measures taken. The aim of this study was to assess the effectiveness of existing uterotonic drugs in the obstetric bleeding prevention and treatment. We performed a detailed systematic analysis of modern domestic and foreign literature on uterotonic drugs being used to prevent and stop obstetric bleeding, with their main parameters considered. The study used such information databases as eLIBRARY.RU, Scopus, PubMed, MEDLINE, ScienceDirect, and Cochrane Library from inception to December 2020. Despite a significant number of studies devoted to exploring the possibilities of uterotonic drugs, currently there are no methods with absolute therapeutic efficacy, which requires research to develop new drugs based on their synthetic analogues.

Journal of obstetrics and women's diseases. 2021;70(1):77-88
pages 77-88 views

The role of dyslipidemia in the pathogenesis of perinatal complications in pregnant women with diabetes mellitus

Kapustin R.V., Tsybuk E.M., Alexeyenkova E.N., Kopteyeva E.V., Arzhanova O.N., Oparina T.I., Tumasova Z.N.

Abstract

HYPOTHESIS/AIMS OF STUDY: The prevalence of diabetes mellitus in pregnant women is increasing. Physiological hyperlipidemia is usually developed during the last third of gestation, increases during pregnancies complicated by diabetes mellitus. Abnormal lipid profiles are associated with adverse perinatal outcomes. However, the associations between maternal dyslipidemia and pregnancy complications in women with different diabetes mellitus types remain unclear. The aim of this study was to assess the lipid profile in women with different types of diabetes mellitus (Type 1, Type 2, and gestational diabetes) based on the therapy in the third trimester of pregnancy, to investigate the associations between serum lipid profile and perinatal complications, and to determine possible prognostic value of lipids in the development of adverse pregnancy outcomes.

STUDY DESIGN, MATERIALS AND METHODS: The study included 277 women who were divided into several groups depending on the type of diabetes mellitus and its therapy method, a group of patients with preeclampsia, and the control group. We analyzed the clinical and laboratory data of outpatient and inpatient cards of pregnant women in the period between 2010 and 2017. Maternal blood samples were collected between 28 and 32 weeks of gestation. The samples were assayed for fasting triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and very-low-density lipoprotein cholesterol concentrations, as well as the atherogenic index of plasma. We also assessed the incidence of gestational arterial hypertension, preeclampsia, intrauterine growth restriction, and preterm birth.

RESULTS: Pregnant women with various types of diabetes mellitus were characterized by a significant rise in serum triglycerides and very-low-density lipoprotein cholesterol levels, an increase in the atherogenic index of plasma, and a significant decrease in antiatherogenic, high-density lipoprotein cholesterol levels. These changes were most pronounced in pregnant women with pregestational diabetes mellitus types and in groups receiving insulin therapy. Correlation analysis revealed weak positive correlations between serum triglycerides concentrations and macrosomia (r = 0.26) and between the atherogenic index of plasma and severe preeclampsia (r = 0.26). The analysis of the ROC curve showed that triglycerides, very-low-density lipoprotein cholesterol, and the atherogenic index of plasma are predictors of severe preeclampsia.

CONCLUSION: Diabetic pregnancies are associated with increased dyslipidemia, which plays an essential role in the pathogenesis of perinatal complications. Evaluating lipid profile markers in the third trimester of diabetic pregnancy may be valid predictors of severe preeclampsia.

Journal of obstetrics and women's diseases. 2021;70(1):89-100
pages 89-100 views

The role of genetic markers of thrombophilia in the structure of the causes of placenta-associated complications in pregnant women with thrombocytopenia

Mysik O.L., Zaynulina M.S., Baranov V.S., Klikunova K.A., Zhivopistseva A.M.

Abstract

HYPOTHESIS/AIMS OF STUDY: Disorders of the hemostatic system continue to occupy one of the leading places in the structure of the causes of infertility and miscarriage. While being associated with reproductive losses, hemostatic disorders are a significant link in the pathogenesis of placenta-associated pregnancy complications. The consumption of platelets and blood clotting factors can be a consequence of inherited thrombophilia and the cause of adverse clinical outcomes of pregnancy. Women with congenital and acquired thrombophilia are at high risk of developing both thrombotic and gestational complications of pregnancy. The aim of this study was to assess the frequency of genetic markers of thrombophilia in pregnant women with thrombocytopenia and to determine the risk of developing obstetric complications depending on thrombophilia gene polymorphisms in the examined women.

STUDY DESIGN, MATERIALS AND METHODS: This multicenter prospective study involved 299 pregnant women in the third trimester of pregnancy. Two groups of patients were included in the study: the main group (n = 249) consisted of individuals with thrombocytopenia, whereas the control group (n = 50) comprised women with normal platelet counts during physiological pregnancy. All patients underwent a complete clinical, anamnestic and laboratory examination. To identify thrombophilia gene polymorphisms, molecular genetic blood testing was conducted using a biochip developed jointly in the Laboratory of Prenatal Diagnostics of Congenital and Hereditary Diseases, the Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott, Saint Petersburg, Russia and the V.A. Engelhardt Institute of Molecular Biology, Moscow, Russia.

RESULTS: The data obtained from a comparative analysis of genetic markers of thrombophilia indicate that the incidence of mutations in the GPIa platelet receptor gene in pregnant women with thrombocytopenia was significantly higher than that in pregnant women with normal platelet counts and physiological pregnancy (42.5% vs. 14.7%; p = 0.003). The frequency of polymorphisms in genes responsible for disorders in the fibrinolytic system (PAI-1, FGB) was also significantly higher than that in the control group (76.4% vs. 47.0%, p = 0.001; 45.7% vs. 23.5%, p = 0.030, respectively).

CONCLUSION: The revealed high frequency of polymorphisms in the platelet receptor genes and genes responsible for disorders of fibrinolysis system in pregnant women with thrombocytopenia may cause platelet hyperaggregation and hypercoagulation, while being a significant risk factor for placenta-associated complications during pregnancy. The variety of genetic defects that may lead to an unfavorable clinical outcome of pregnancy dictates the need for further study.

Journal of obstetrics and women's diseases. 2021;70(1):101-108
pages 101-108 views

Main characteristics of IVF / ICSI protocols in patients with suboptimal response to controlled ovarian stimulation

Tuan N.C., Dzhemlikhanova L.K., Makhmadaliyeva M.R., Kogan I.Y., Niauri D.A., Krikheli I.O., Obyedkova K.V., Safaryan G.K., Mekina I.D., Lesik E.A., Ishchuk M.A., Gzgzyan A.M.

Abstract

HYPOTHESIS/AIMS OF STUDY: According to the number of oocytes retrieved in IVF/ICSI protocols, the ovarian response to controlled ovarian stimulation is divided into: poor (0–3 oocytes), suboptimal (4–9 oocytes), normal (10–15 oocytes) and excessive (>15 oocytes) response. However, the effectiveness of IVF / ICSI programs in women with a suboptimal response is poorly understood, since this cohort of patients is often fallen into the category of women with a normal response. The aim of this study was to determine the main characteristics of IVF / ICSI programs in patients with suboptimal response to be further compared to those in women with normal response to controlled ovarian stimulation.

STUDY DESIGN, MATERIALS AND METHODS: This retrospective study included 568 patients: 470 women with suboptimal response and 98 women with normal response to controlled ovarian stimulation. The comparative analysis comprised clinical and anamnestic data, as well as the main characteristics of assisted reproductive technology programs in the selected clinical groups.

RESULTS: It was found that patients with suboptimal response to controlled ovarian stimulation had significantly more frequent history of pelvic surgery (71.3 % vs. 55.1 %; p < 0.01) and pelvic inflammatory diseases (70.9% vs. 60.2%; p < 0.05). Parameters of ovarian reserve (serum anti-Müllerian hormone level and antral follicle count) in women with suboptimal response were significantly lower (p < 0.001). In addition, the number of mature oocytes, 2PN zygotes, good quality embryos (p < 0.001), as well as the clinical pregnancy rate in women with suboptimal response were found to be significantly lower than in patients with normal response to controlled ovarian stimulation (27.2% vs. 41.7%; p < 0.01). It was noted that concomitant uterine fibroids enhanced the negative impact on the effectiveness of IVF / ICSI programs in women with suboptimal response to controlled ovarian stimulation (OR = 0.5; 95% CI: 0.3–0.9; p = 0.03). ROC analysis identified predictors of suboptimal response to controlled ovarian stimulation, such as serum anti-Müllerian hormone level (AUC = 0.80) with the cut-off value of ≤2.57 ng / ml (sensitivity 74%, specificity 75%) and antral follicle count (AUC = 0.90) with the cut-off value of ≤10 follicles (sensitivity 80%, specificity 94%).

CONCLUSION: In women with suboptimal response to controlled ovarian stimulation, IVF / ICSI success rates are significantly reduced when compared to those in women with normal response. Concomitant uterine fibroids may further decrease the effectiveness of IVF / ICSI protocols in patients with suboptimal response. Predictors of suboptimal response include the serum anti-Müllerian hormone level and antral follicle count.

Journal of obstetrics and women's diseases. 2021;70(1):109-118
pages 109-118 views

Current public health problems

Monitoring in obstetric critical care (“maternal near miss”) in the Northwestern Federal District of the Russian Federation in 2018-2019

Bezhenar V.F., Filippov O.S., Adamyan L.V., Nesterov I.M.

Abstract

This article presents data of monitoring critical obstetric conditions (maternal near miss) for the purpose of auditing the quality of medical care and prevention of maternal mortality, obtained on the basis of an analysis of statistical data from eleven federal subjects of the Northwestern Federal District of the Russian Federation for 2018-2019. We characterized the critical obstetric conditions that allow avoiding maternal mortality cases, which, in modern legal practice, most often require forensic examinations on the fact of providing obstetric and gynecological medical care of inadequate quality. We determined that the main causes of maternal mortality cases (83.1% in 2018 and 84.0% in 2019) were massive obstetric bleeding and complications of severe preeclampsia, which more often occurred during childbirth and the first days of the postpartum period. All patients who survived a near death condition belonged to the group of high obstetric and perinatal risk, but most of them were delivered in obstetric hospitals of the second level, with more than half of the women by caesarean section.

We discussed the main ways of preventing and reducing the incidence of critical obstetric conditions and maternal mortality based on the improved modern integral model of internal quality control of medical care in obstetric institutions. We also discussed the findings based on the introduction into practice of medical, organizational and methodological (including telecommunication and other) technologies aimed at increasing professional competencies in the regions of the country. Special attention is drawn in this article to the need to systematize and develop uniform and clear criteria for assessing critical obstetric conditions.

Journal of obstetrics and women's diseases. 2021;70(1):5-18
pages 5-18 views

Current relevance of non-invasive prenatal study of cell-free fetal DNA in the mother’s blood and prospects for its application in mass screening of pregnant women in the Russian Federation

Kalashnikova E.A., Glotov A.S., Andreyeva E.N., Barkov I.Y., Bobrovnik G.Y., Dubrovina E.V., Zhuchenko L.A.

Abstract

This review article offers an analysis of application of cell-free fetal DNA non-invasive prenatal screening test for chromosome abnormalities in the mother’s blood in different countries. The diagnostic capacities of the method, its limitations, execution models and ethical aspects pertinent to its application are discussed. The data for the discordant results is shown and analyzed. The advantages of the genome-wide variant of cell-free fetal DNA analysis and the problems concerning its application in the mass screening are described. The main suggestion is to implement the contingent cell-free fetal DNA testing model for the common trisomies (for the chromosomes 21, 18 and 13) into the prenatal diagnostic screening programs in the Russian Federation. This novel model is based on the results of the mass combined first trimester prenatal screening in four federal subjects of the country completed by 2019 and is offered as an additional screening in the mid-level risk group (with cut-off from 1 : 100 to 1 : 500 or from 1 : 100 to 1 : 1000) defined according to the first trimester prenatal screening results. The basic requirements for the implementation of the contingent model in the Russian Federation are stated.

Journal of obstetrics and women's diseases. 2021;70(1):19-50
pages 19-50 views


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