Physiological Course Of Pregnancy Research Articles

Complex applying physical therapy and preformed physical factors in pregnant women with chronic pyelonephritis

The aim of the work is to evaluate the impact of physical therapy and preformed physical factors in pregnant women with chronic pyelonephritis on central hemodynamic indicators. Materials and methods. The dynamics of 134 pregnant women with chronic pyelonephritis (CP) in the remission stage, who underwent a complex sanatorium rehabilitation program, were examined. The main study group consisted of 79 pregnant women with chronic pyelonephritis. In this contingent of women, the sanatorium rehabilitation complex additionally included a course of intermittent normobaric hypoxytherapy (INH). The comparison group consisted of 55 pregnant women with CP, for whom the sanatorium rehabilitation complex did not include an INH course. The control group is represented by 37 somatically healthy women with a physiological course of pregnancy. All pregnant women were examined for central hemodynamic (CH) indicators using the computer diagnostic complex REOKOM (Kharkiv). Results. Pregnancy periods of 20–30 and 31–30 weeks in women with CP are characterized by a pathological load on central hemodynamics. At the same time, the application for the INH course in the sanatorium rehabilitation complex (the main group) allows for an increase in the compensatory capabilities of the pregnant woman with CH. Thus, in the period of pregnancy of 22–30 weeks in the main group, indicators of diastolic blood pressure and heart rate were probably lower than the control values (P < 0.001), which in this group is determined by values of peripheral resistance of blood vessels close to those of the control group (P > 0.05), regardless of the timing of the study. The study of CH and the comparison of different periods of gestation and between research groups indicate an inverse relationship between indicators that reflect the intensity of cardiohemodynamics and indicators of vascular resistance, as one of the final mechanisms of maintaining blood pressure at a physiological level, or its pathological increase in chronic pyelonephritis and preeclampsia Taking into account that the ratio of cardiac index indicators and total peripheral vascular resistance in all study groups was stable and directly dependent on the level of blood pressure, it is advisable to recommend for practical application in order to assess the state of CH of pregnant women with CP indicators of stroke or cardiac indices, which characterize the intensity cardiohemodynamics and do not depend on the anthropometric data of the pregnant woman. Conclusions. The application of physical therapy and preformed physical factors, namely, intermittent normobaric hypoxytherapy in pregnant women with chronic pyelonephritis in a complex program of sanatorium rehabilitation increases the compensatory capabilities of the cardiovascular system, which is confirmed by a significant decrease in the values of the total peripheral resistance against the background of an increase in the cardiac index.

PECULIARITIES OF THE FORMATION OF THE FUNCTIONAL SYSTEM "MOTHER- PLACENTA-FETUS" BY THE INFLUENCE OF SMALL DOSES OF RADIATION

Introduction. 137Cs ecosystem pollution is a source of radiation for humans. Undifferentiated cells capable of rapid division are the most vulnerable to ionizing radiation. Therefore, the fetoplacental and immune systems should be expected powerful responce to ionizing radiation. The functional capacity of the placenta determines pregnancy scenarios.Aim: to study the features of the formation of the fetoplacental system under the influence of low doses of radiation. Materials and methods. Pregnant women were in two groups, according to the design. The main (1) group included 60 women with reproductive losses in their history and a threat of termination to the current pregnancy, control (2) group consisted of 30 women with a physiological course of pregnancy and an uncomplicated anamnesis. The found incorporation of 137Cs in the placentas of the women of the studied groups was on β-spectrometry. The nature of placental damage was studied using the pathomorphological examination. The expressions of vimentin and CEA were studied in the structures of the placenta using immunohistochemistry. The effects of radiation on the functional system "mother-placenta-fetus" was determined in immunological, hormonal, biochemical, and bacteriological studies.The study was approved by the Medical Ethics Commission of the State Institution "Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of the National Academy of Medical Sciences of Ukraine" (Protocol No. 3 of 07.06.2017). The results were statistically processed on a PC using Microsoft Excel-2016 using Fisher's angular transformation criterion. Differences in comparative values are considered probable if p < 0.05 (probability index more than 95%).The research was carried out as a fragment of the research work of the State Institution "Institute of Pediatrics, Obstetrics and Gynecology named after Academician O.M. Lukyanova of the National Academy of Medical Sciences of Ukraine" "To develop the latest and improve existing technologies for the diagnosis, prevention and treatment of premature abortion in women with miscarriage, taking into account the placenta passport" (2018-2020). Code ВН.20.00.02.18, state registration number 0118U000039, КПКВ 6561040.Research results. According to the results, chronic radiation stress plays a decisive role in the multifactorial nature of placental dysfunction and antenatal losses. Activity up to 1.0 Bq/kg of 137Cs does not affect the course of gestation. The compensatory capacity of the placenta remains preserved at the accumulation of 1.1 to 4.4 Bq / kg of 137Cs. It is possible to prolong the pregnancy until term delivery. As a result of exposure to 4.5-10.4 Bq/kg of 137Cs, the stroma of the maternal surface of the placentas is damaged. At the same time, the pregnancy is terminated prematurely, at 28-36 weeks + 6 days, but thanks to the preservation of compensatory reactions in the placenta, the children are born alive. Accumulation in placentas of more than 10.4 Bq/kg of 137Cs is a probable factor in antenatal death of the fetus and early premature birth, as both maternal and fetal structures of the placenta are damaged.Conclusions. Internal irradiation by incorporated 137Cs damages the architecture of the placenta, which complicates the course of gestation. Extreme effects depend on the volumetric activity incorporating 137Cs and compensatory placental properties. The placental accumulation of 4.5 to10.4 Bq / kg of 137Cs triggers premature labor. Accumulation in the placenta of more than 10.4 Bq / kg 137Cs is a probable factor in antenatal fetal death and premature birth. An imbalance of steroid hormones and peroxide hemostasis system are predictors of placental dysfunction and termination of pregnancy. Expression of vimentin is a marker of placental destruction by internal exposure to radionuclides. Expression of CEA is a marker of premature birth and the antenatal death of the fetus.

Natural Killer Cell Derived Microvesicles Affect the Function of Trophoblast Cells.

The interaction of natural killer (NK) and trophoblast cells underlies the formation of immune tolerance in the mother-fetus system and the maintenance of the physiological course of pregnancy. In addition, NK cells affect the function of trophoblast cells, interacting with them via the receptor apparatus and through the production of cytokines. Microvesicles (MVs) derived from NK cells are able to change the function of target cells. However, in the overall pattern of interactions between NK cells and trophoblasts, the possibility that both can transmit signals to each other via MVs has not been taken into account. Therefore, the aim of this study was to assess the effect of NK cell-derived MVs on the phenotype, proliferation, and migration of trophoblast cells and their expression of intracellular messengers. We carried out assays for the detection of content transferred from MV to trophoblasts. We found that NK cell-derived MVs did not affect the expression of CD54, CD105, CD126, CD130, CD181, CD119, and CD120a receptors in trophoblast cells or lead to the appearance of CD45 and CD56 receptors in the trophoblast membrane. Further, the MVs reduced the proliferation but increased the migration of trophoblasts with no changes to their viability. Incubation of trophoblast cells in the presence of MVs resulted in the activation of STAT3 via pSTAT3(Ser727) but not via pSTAT3(Tyr705). The treatment of trophoblasts with MVs did not result in the phosphorylation of STAT1 and ERK1/2. The obtained data indicate that NK cell-derived MVs influence the function of trophoblast cells, which is accompanied by the activation of STAT3 signaling.

ДВИГАТЕЛЬНАЯ АКТИВНОСТЬ ПЛОДА И МОРФОЛОГИЧЕСКИЕ ОСОБЕННОСТИ ТКАНИ ПЛАЦЕНТЫ У ПАЦИЕНТОК С РАННЕЙ И ПОЗДНЕЙ ПРЕЭКЛАМПСИЕЙ

The study aims to analyze the features of fetal motor activity and afterbirths’ common pathomorphological differences in women with early and late preeclampsia living in areas equated to the conditions of the Far North (Khanty-Mansi Autonomous Okrug – Ugra). The study examined 385 labor cases of patients who were classified as follows: 131 patients with early onset of preeclampsia (up to 34 weeks), 144 patients with late onset of preeclampsia (after 34 weeks), and 110 apparently healthy patients with the physiological course of pregnancy. The analysis of fetal motor activity and morphological studies of the afterbirths was carried out. When applying subjective and objective fetal movements counting methods, patients with early preeclampsia had statistically significantly lower fetal motor activity and more cases of chorionic villous maturation disorder, chorangiosis, myocardial infarctions, and placental pseudoinfarctions. Ascending infection of the placenta prevails in both early and late-onset preeclampsia.

ETIOLOGICAL FACTORS IN DISEASES OF HARD TISSUES AND PERIODONTIUM IN PREGNANT WOMEN

Pregnant women have one of the highest risks of dental disease [3]. According to a number of authors, during the physiological course of pregnancy, the prevalence of dental caries is 91.4%, periodontal tissue diseases occur in 90% of cases, lesions of previously intact teeth with a predominantly acute course of the carious process - in 38% of pregnant patients [5 ]. Secondary caries, progression of the carious process, enamel hyperesthesia occurs in 79% of pregnant women [11]. At the same time, the intensity of the increase in dental caries in terms of the absolute increase in the index of caries-filling-removal during the gestational period is 0.83 [2]. In 50% of pregnant women and women in labor, the so-called gingivitis of pregnant women is observed during the normal course of the gestational period already at 2-3 months of pregnancy [12]. From the second half of pregnancy, the pathological process becomes more pronounced and more often proceeds as a generalized catarrhal or hypertrophic gingivitis, and pyogenic granuloma often develops. As pregnancy progresses, periodontal disease progresses continuously, and only in the postpartum period does the clinical picture improve [4]. In the long term, gingivitis that occurs during pregnancy becomes chronic [9, 10]. In a pregnant woman, against the background of altered reactivity and reduced body resistance, latent odontogenic foci of infection can lead to serious complications as a result of exacerbation of the inflammatory process [7, 8]. The greatest severity of inflammatory phenomena in periodontal tissues occurs in the second trimester of pregnancy, and the critical increase in the cariogenic situation in the oral cavity occurs in the third trimester [4, 2], which not only determines the optimal timing of dental examinations during pregnancy and the postpartum period, but also the differentiation of the approach to programs for the prevention and treatment of the most significant diseases of the oral cavity for this period of pregnancy. The decisive role in the development of caries and periodontitis in pregnant women belongs to hormonal substances (somatomammotropin, progesterone, gonadotropin) produced by the placenta, changes in mineral and protein metabolism, immunological status, oral microflora [1, 5]. The timing of the increased risk of the onset and progression of periodontal diseases, as well as the increase in the intensity of dental caries in pregnant women, is not enough to state; tires. This does not negate the significance of already established factors affecting the occurrence and development of dental caries, periodontal disease during pregnancy, but is aimed at competently combining diagnostically important known and newly identified criteria into a system of practical recommendations for identifying risk groups among pregnant women. on dental health and special monitoring of them. Immunoprotective peptides of biological media, including oral fluid, are markers of the intensity of local inflammation and are responsible for the implementation of innate antimicrobial immunity [6, 12]. In the oral fluid, a whole complex of immunoprotective peptides is isolated, among which lactoferrin, cathelicidin LL-37, and α-defensin are distinguished [14]. The inclusion of immunoprotective peptides in algorithms and models for ranking the risk of progression of dental caries during pregnancy will expand the boundaries of existing recommendations in this direction. When studying systemic immunity in pregnant women with periodontal diseases, oral fluid and peripheral blood are used as biological media [8]. At the same time, retroplacental blood and umbilical cord blood containing fetal and maternal blood, despite the easy method of selection after the birth of a child and placenta, not associated with invasive manipulations, is not used as a biological medium. Meanwhile, the determination of the spectrum of inflammatory mediators, the mineral composition of retroplacental and umbilical cord blood will allow answering the questions whether inflammation of the periodontal tissues of varying severity was accompanied by the "mother-placenta-fetus" system, whether it is possible to predict from the stage of childbirth in the future the appearance of caries of milk teeth? The purpose of this study is to optimize the system of providing dental care to pregnant women using clinical and laboratory indicators.

FEATURES OF THE FUNCTIONAL MORPHOLOGY OF THE FULL-TERM PLACENTA IN WOMEN WITH THREATENED ABORTION WITH BLEEDING IN THE FIRST TRIMESTER OF GESTATION.

The aim: To examine the morphology regarding the term placentas in pregnancies with threatened abortion with bleeding in the first trimester. Materials and methods: 118 term placentas were selected, of which 40 placentas with the physiological course of pregnancy. 78 placentas were from women with threatened abortion with bleeding in the first trimester, of which 37 patients received hormonal therapy (group I), 41 women were prescribed symptomatic therapy (group II). Placentas were investigatedaccording to the protocol, which includes organometric, macroscopic and microscopic studies. Results: In the placentas of group II is a significant increase of the area of terminal villi compared due to the stroma against the background of a deficit of fetal capillaries. In group I have revealed that the specific weight of the vascular bed of the terminal villi was 1.5 times higher compared to the control (Р=0.031) and 2.7 times higher than the group II (Р=0.022) and dominates the share of the stroma. The weight of the epithelium of the terminal villi in all groups is approximately the same (Р=0.042), but the ratio of the epithelium to the stroma is higher in the group I (0.63) than in the control (0.43). Conclusions: In women with a pathological course of the first trimester of pregnancy the compensatory mechanisms in full-term placentas are morphologically represented by an increase in the number of terminal villi, syncytio-capillary membranes, intensification of angiogenesis. In the placentas of women who received hormonal therapy adaptive reactions are most effective and able to compensate for the gestational immaturity of the chorion.

The role of mast cells in physiological and complicated pregnancy

Mast cells (MCs) are highly differentiated and multifunctional immune cells. The importance of TC has been established not only as mediators of allergic reactions, but also for the development of an immune response, the occurrence of certain autoimmune diseases, tissue homeostasis, the formation of immunotolerance and metastasis of malignant tumors. MCs are present in the endometrium of women in various value depending on age, the phase of the menstrual cycle, the presence of pregnancy. Out of pregnancy, MCs are involved in the cyclic transformation of the uterine mucosa. At the onset of pregnancy, MCs stimulate the process of remodeling of the spiral arteries, the production of leukemia-inhibiting factor (LIF), which is the main implantation factor, and contribute to the formation of an immunotolerant state of the mother in relation to the fetus. Obstetric complications are accompanied by a variable content of MCs, which is associated with different genesis of diseases. A low amount of MCs is associated with impaired implantation and the development of early preeclampsia, an increased content of MCs is observed in the presence of a pathological inflammatory reaction that accompanies late preeclampsia. This review is devoted to the significance of MCs and their mediators in the physiological course of pregnancy, as well as their participation in the pathogenetic mechanisms of pregnancy complications.

PREGNANT WOMEN WITH COVID-19 AND PLACENTA ANGIOGENESIS

Aim of our research was to conduct a clinical and laboratory analysis of the impact of COVID-19 on pregnancy and the condition of the fetus. Materials and Methods: At the first stage, we conducted a retrospective examination of 50 pregnant women treated at Ternopil Municipal Hospital No.2 (Ukraine) between November 2020 and January 2022 with the history of COVID-19, confirmed by PCR test, and 25 pregnant COVID-19 negative pregnant women (control group). At the second stage, we performed prospective cohort study and involved 40 pregnant women treated with the history of COVID-19, confirmed by PCR, and 10 pregnant COVID-19 negative women with a physiological course of pregnancy as a control group.Women were divided into the following groups: group I -10 women diagnosed with COVID-19 during the first trimester of pregnancy: group II-15 women diagnosed during the second trimester; group III-15 women diagnosed during the third trimester. Ultrasound examination and cardiotocograms were performed to assess fetus status. Blood samples were collected at delivery. To determine whether COVID-19 could alter placental angiogenesis, vascular endothelial growth factor A (VEGFA), PlGF and interleuin-32-α were assessed. Results: We identified that concentration of VEGFA was 95.30±5.65 pg/ml in control group. In women who had COVID-19 in first trimester, this index was 1.3 times higher, in second trimester 1.63 times higher and in third trimester by 2 times compared to control group. PlGF concentration was only 27,4 percent in group I, 16 percent in group II and 30 percent in group III,compared to control group. Concentration of interleuin-32-α was 67.27±5.63 pg/ml in control group and increased to 167 percent in group I, by 2.8 times in group II and by 6.3 times in group III compared to control group. Conclusions: COVID-19 has a negative impact on placental angiogenesis, including VEGFA and PlGF. Fetal post-COVID-19 syndrome requires timely diagnosis of disorders and further study. Post-COVID-19 syndrome is an immune-dependent pathology in which the processes of protracted cytokine activation occur in the body of a pregnant woman.

Diagnostic significance of autoantibody combination in fetal growth restriction with early and late manifestation

BACKGROUND: Fetal growth restriction (FGR) is one of the current problems in modern obstetrics and perinatology, which is associated with a large number of adverse perinatal outcomes.
 AIM: This study aimed to assess the diagnostic significance of the combination of autoantibodies (AAB) in the early and late FGR manifestation.
 MATERIALS AND METHODS: The study involved 117 pregnant women, classified into Group 1 (90 women with FGR) and Group 2 (27 women with a physiological course of pregnancy). Pregnant women with FGR were divided into two subgroups depending on the time of manifestation, i.e. FGR subgroups with early and late manifestation (45 patients each), respectively. Upon hospital admission, all patients of the study groups had blood sampling to determine autoimmune AABs using the ELI-P-test.
 RESULTS: An isolated increase in AABs to human chorionic gonadotropin (hCG) antigen, TrM (AAB markers of changes in vascular and hemostasis system), S100 protein, antineutrophil cytoplasm antibodies (ANCA), and KiMS (AABs to the cytoplasmic antigen of glomerular kidney cells) were observed in the early FGR manifestation when comparing the abnormal AAB spectrum in the early and late FGR manifestation, while a statistically significant isolated increase in the level of AABs to DNA and insulin was found in the late FGR manifestation.
 CONCLUSIONS: The study revealed the diagnostic significance of AAB combinations, as well as the combinations of increased AAB levels to hCG, S100, ANCA, and KiMS and an increase in AABs to DNA, collagen, and S100 protein in the early and late FGR manifestation, respectively.

Placenta: an organ with high energy requirements

Placenta is a unique organ, without which the very phenomenon of human pregnancy is impossible. Semiallogeneous nature, localization of the placenta, complex and heterogeneous cellular composition determines its complex and multifaceted role in the course of physiological pregnancy, indicates the importance of studying this organ in a number of reproductive pathologies. The purpose of this review was to analyze the literature sources illustrating the importance of energydependent processes in placental metabolism and to determine the molecular basis of placental energy conversion. Publications of foreign and Russian authors from PubMed database and scientific electronic library eLIBRARY.ru were used when writing the review. The review highlights the main functions of the placenta: transport and synthetic functions in terms of their place in the structure of energy expenditure of the organ. The systems by which the transport of ions and gases from maternal blood through the placental barrier is performed, are considered. The role of the placenta in the synthesis of steroid hormones and glucocorticoids is detailed. The main bioenergetic systems are also considered: placental glucose metabolism, the functional activity of mitochondria and the creatine kinase system of the placenta. These data allow us to put the placenta on a par with other organs with high energy requirements (brain, transverse striated skeletal muscles, heart, kidneys, liver), which are most susceptible to metabolic disorders. Maintaining a balance between expenditure and synthesis of macroergic compounds in the placenta is critical for an adequate course of physiological pregnancy, and imbalances can lead to such pathologies as fetal retardation syndrome or preeclampsia. Further study of placental energy supply systems seems important for understanding the mechanisms of intrauterine development disorders and developing their pathogenetic treatment.

MORPHOLOGICAL FEATURES OF STRESS MARKERS IN PLACENTA

Introduction. The multinucleated syncytiotrophoblast of human placental villi is responsible for transport functions between thematernal and fetal circulation and is the main site of protein synthesis and steroid production. It is formed by the fusion of underlyingcytotrophoblast cells. The nuclei of the multinucleated syncytiotrophoblast are nonmitotic, but the mechanism of cell cycle arrest in thesyncytiotrophoblast is not known. Single publications have described that cell fusion induces a cellular senescence, best known as acomponent of the stress response and an important factor in preventing tumor cell growth. For syncytiotrophoblast, one of the criteriaof its aging is the formation of so-called syncytial nodes - local accumulations of nuclear material with protrusion of these cells into theinterstitial space.The purpose of the study. To determine the morphological features in women's placentas under the influence of chronic stresscaused by coronavirus disease and internal irradiation, with the subsequent formation of criteria for diagnosing diseases and assessingthe severity of lesions in the mother and fetus.Material and methods. A morphological study of syncytial nodules in the villi of the placenta of groups of women with chronic stressdue to internal irradiation and COVID-19 (classified by severity of the disease) was performed in comparison with the physiologicalcourse of pregnancy and childbirth. Histopathological and ultrastructural examination of placentas was performed with the detection ofsyncytial nodes with morphometric analysis of their ultrastructural features of the nuclear component of syncytiotrophoblast nodules andtheir comparison in clinical groups. The number of syncytial nodes was estimated on histological specimens stained with hematoxylinand eosin. The effect of chronic stress in women was significantly (p<0.05) confirmed by increased cortisol levels (saliva test). Statisticalprocessing of the results was carried out using licensed programs «Microsoft Excel» and «Statistica». The design of the study and allmethods used in this study were reviewed and approved by the Bioethics Committee of the State Institution «Institute of Pediatrics,Obstetrics and Gynecology named after Academician O.M. Lukyanova of the National Academy of Medical Sciences of Ukraine», Kyiv,Ukraine.Results of the study. Morphological examination of the placental tissue of parturient women with COVID-19 showed an increasein the number of syncytial nodes in the villi, which we associated with the presence of stress. Ultrastructural studies revealed changes inthe nuclei of syncytial nodules depending on the pathology.Conclusion. An increase in the number of syncytial nodes in the chorionic structures in internal radiation and COVID-19 in pregnantwomen has been established, which is important as predictors of placental factors for the health of the individual in the future.

Clinical significance of hemostasiological screening for thrombophilia in pregnant women with former thrombosis

Introduction . Pregnancy management in post-thrombotic women is challenging, because women with previous episode of venous thromboembolic complications (VTEC) have a 3–4 times higher risk of its exacerbation during than outside of subsequent pregnancies. Aim : to improve effective prenatal counseling program for women with former venous thrombosis and ischemic stroke to prevent recurrence of arterial and venous complications as well as pregnancy outcomes for mother and fetus. Materials and Methods . A single-center observational study was conducted involving 50 patients with arterial and venous thrombosis and pregnancy complications in anamnesis and 40 patients with a physiological course of pregnancy. To improve existing methods of thrombosis prevention, risk factors such as gene polymorphisms for plasminogen activator inhibitor-1 (PAI-1), coagulation factor II (prothrombin; F2: Thr165Met), coagulation factor I (fibrinogen; FGB I/D) were investigated as potential new candidates of thrombosis risk markers in pregnant women and puerperas. Results . In 24 (48 %) of 50 women with former arterial and venous thrombosis and pregnancy complications, were found to develop thromboembolic complications during pregnancy. Risk assessment performed according to the existing thrombosis risk scales, revealed that only 7 (29.2 %) patients were considered as candidates for thromboprophylaxis and received anticoagulant therapy. The remaining 17 women who subsequently developed thrombosis received no anticoagulant therapy. Unfortunately, most women were not tested for thrombophilia despite a history of pregnancy complications (fetal loss, preeclampsia, fetal growth retardation). The hereditary thrombophilia of high thrombogenic risk occurred in 5 (20.8 %) of 24 women with thrombosis during pregnancy (3 – homozygous forms of factor V Leiden mutation, 1 – reduced protein C and 1 – deficiency of protein S and antithrombin). Circulation of various types of antiphospholipid antibodies was found in 13 (54.2 %) of 24 women. Homozygous polymorphisms of the PAI-1 4G/4G (45.8 %) and prothrombin F2 Thr165Met (20.8 %) genes were significantly more common in women with former thrombosis and obstetric complications compared with the control group (p < 0.001 and p = 0.023, respectively; odds ratio = 6.744; 95 % confidence interval = 1.195–38.056). Conclusion . In all cases examined, 24 women with thrombosis during pregnancy revealed to suffer from hereditary or acquired thrombophilia of high thrombogenic risk. After exclusion of high-risk thrombophilia, a number of gene polymorphisms exist that may be new candidates as a risk factor for thrombosis in pregnant women. More than 50 % of thrombosis cases in our study were associated with the homozygous genotype PAI-1 4G/4G (p < 0.001) and F2 Thr165Met (p < 0.001).

Platelet hemostasis in the implementation of placental dysfunction

The objective: to study the state of the platelet link of hemostasis in pregnant women with placental dysfunction. Materials and methods. A clinical and laboratory analysis of 54 patients with placental dysfunction was carried out. The control group included 30 practically healthy women with a physiological course of pregnancy. Venous blood of the patients was collected for testing using vacuum systems in tubes with 3.8% sodium citrate. The functional activity of platelets was studied on a photooptical aggregometer AP2110 (Solar, Belarus), thrombocytogram was performed on a hematological analyzer H18 LIGHT (SFRI SAS, France), thromboelastometric tests were determined on the ROTEM delta system (Tem Innovations GmbH, Germany). Results. Platelet hemostasis has a significant effect on maximum clot firmness (MCF) according to ROTEM results in patients with placental dysfunction. This indicator can be effective in determination of the hyperreactivity of the platelet unit in patients with placental dysfunction. Although no statically significant difference was found in the optical aggregometry indicators induced by ADP and collagen between the patients with placental dysfunction and the control group, a clear tendency to a sharp reduction in the lag-period of collagen-induced platelet aggregation in patients with placental dysfunction should be mentioned. Conclusions. Disorders in the platelet chain of hemostasis can play a significant role in the formation of a thrombophilic state in patients with placental dysfunction, as well as the damage of the endothelium and coagulation changes. The use of a test based on collagen-induced platelet aggregation may be a perspective method for effective diagnosis of platelet hyperreactivity. The study of the platelet link should become an additional element of the laboratory examination in order to resolve the issue of the need to prescribe antiplatelet agents to prevent the development of placental dysfunction.

Placental proteome in late‑onset of fetal growth restriction.

Fetal growth restriction (FGR) occurs when the fetus does not reach its genetically programmed intrauterine potential for growth and affects ~5–10% of pregnancies. This condition is one of the leading causes of perinatal mortality and morbidity associated with obstetric and neonatal complications. Placental dysfunction in FGR causes an impairment in the transfer of nutrients and oxygen from the mother to the developing fetus. Maternal adaptations to placental insufficiency may also play a role in the pathophysiology of FGR. The present study aimed to compare the proteome of the placentas of 18 women with the physiological course of pregnancy and eutrophic fetus [estimated fetal weight (EFW) >10th percentile; control group] and 18 women with late FGR (EFW <10th percentile) diagnosed after 32 weeks of pregnancy, according to the Delphi consensus (study group). The U. Mann-Whitney test was used to compare two independent groups. The R. Spearman correlation coefficient significance test was used to assess the existence of a relationship between the analyzed measurable parameters. P<0.05 was considered to indicate a statistically significant difference. The tests showed the presence of 356 different proteins which were responsible for the regulation of gene transcription control, inhibiting the activity of proteolytic enzymes, regulation of trophoblast proliferation and angiogenesis and inflammatory response. In the FGR placental proteome, other detected proteins were mostly involved in response to oxidative stress, cellular oxidation and detoxication, apoptosis, hemostatic and catabolic processes, energy transduction protein interactions, cell proliferation, differentiation and intracellular signaling. The present study used chromatographic mass-spectrometry to compare the placental proteome profiles in pregnancies complicated by late-onset FGR and normal pregnancy. Comparative analysis of proteomes from normal and FGR placentas showed significant differences. Further research is needed to clarify maternal and fetal adaptations to FGR.

Features of the Maternal Metabolom in Fetal Growth Delay

Цель. Изучить особенности метаболома у беременных с задержкой роста плода.Материалы и методы. В ходе исследования изучены образцы плазмы крови 41 женщины. Беременные были разделены на группы: 1-ю группу составила 21 беременная с задержкой роста плода, 2-ю группу – 20 женщин с физиологическим течением беременности. Анализ образцов был осуществлен с помощью высокоэффективной жидкостной хроматографии. Статистическая обработка полученных данных осуществлялась с использованием пакета программ Statistica 10.0 (SN – AXAR207F394425FA-Q).Результаты. У пациенток с задержкой роста плода в плазме крови выявлено статистически значимое повышение 14 аминокислот и их производных по сравнению с контрольной группой: цистеиновой кислоты (СА), фосфосерина (PSer), аспарагина (Asn), серина (Ser), треонина (Thr), 1-метилгистидина (1MHis), 3-метилгистидина (1MHis), аргинина (Arg), симметричного диметиларгинина (SDMA), α-аминомасляной кислоты (αАВА), β-аминомасляной кислоты (βАВА), метионина (Met), триптофана (Trp), лейцина (Leu). Выявлена умеренная корреляционная связь массы плода с уровнем цистеиновой кислоты (СА), фосфосерина (PSer), серина (Ser), 3-метилгистидина (3MHis), треонина (Thr), аланина (Ala), таурина (Tau), симметричного диметиларгинина (SDMA), α-аминомасляной кислоты (aABA), β-аминомасляной кислоты (βАВА), триптофана (Trp); сильная корреляционная связь определена с аспарагином (Asn).Заключение. Полученные результаты обосновывают перспективность изучения метаболомики в качестве диагностических маркеров задержки роста плода. Purpose. To study the features of the metabolome in pregnant women with fetal growth retardation.Materials and methods. During the study, blood plasma samples from 41 women were studied. The pregnant women were divided into groups: the 1st group consisted of 21 pregnant women with fetal growth retardation, the 2nd group – 20 women with a physiological course of pregnancy. Samples were analyzed by high performance liquid chromatography. Statistical processing of the obtained data was carried out using the Statistica 10.0 software package (SN – AXAR207F394425FA-Q).Results. In patients with fetal growth retardation in blood plasma, a statistically significant increase in 14 amino acids and their derivatives was revealed compared to the control group: cysteic acid (CA), phosphoserine (PSer), asparagine (Asn), serine (Ser), threonine (Thr), 1-methylhistidine (1MHis), 3-methylhistidine (1MHis), arginine (Arg), symmetrical dimethylarginine (SDMA), α-aminobutyric acid (αABA), β-aminobutyric acid (βABA), methionine (Met), tryptophan (Trp), leucine (Leu). A moderate correlation was found between fetal weight and the level of cysteic acid (CA), phosphoserine (PSer), serine (Ser), 3-methylhistidine (3MHis), threonine (Thr), alanine (Ala), taurine (Tau), symmetrical dimethylarginine (SDMA), α-aminobutyric acid (aABA), β-aminobutyric acid (βABA), tryptophan (Trp); a strong correlation was determined with asparagine (Asn).Conclusion. The results obtained substantiate the prospects of studying metabolomics as diagnostic markers of fetal growth retardation.

Inflammation-Related Molecules at the Maternal-Fetal Interface during Pregnancy and in Pathologically Altered Endometrium.

The blastocyst expresses paternally derived alloantigens and induces inflammation during implantation. However, it is necessary for the onset of pregnancy. An abnormal response might result in a pathological course of pregnancy or pregnancy failure. On the other hand, a state of maternal immune tolerance is necessary to ensure the normal development of pregnancy by suppressing inflammatory processes. This article discusses recognized mechanisms and the significance of inflammatory processes for embryo implantation and pregnancy establishment. We would also like to present disorders involving excessive inflammatory response and their influence on events occurring during embryo implantation. The chain of correlation between the processes responsible for embryo implantation and the subsequent physiological course of pregnancy is complicated. Many of those interrelationships are still yet to be discovered. Undoubtedly, their recognition will give hope to infertile couples for the emergence of new treatments that will increase the chance of giving birth to a healthy child.

Clinical significance of assessing autoantibody level in diagnostics of early and late fetal growth retardation

Aim: to analyze diagnostic potential of early and late fetal growth retardation (FGR) based on examining significance of serum autoimmune antibody (АВ) level.Materials and Methods. A single center prospective cohort comparative study included 98 pregnant women: 79 with FGR (main group I) and 19 with physiological course of pregnancy (comparison group II). Depending on the time of manifestation, pregnant women with FGR were divided into 2 subgroups: early FGR (subgroup IA, n = 41) and late FGR (subgroup group IB, n = 38). All patients underwent venous blood sampling to determine the serum autoimmune AB level against 12 human self-antigens using the ELI-P-Test: for human chorionic gonadotropin antigen (hCG), DNA, β2-glycoprotein (β2-GP), collagen, fragment crystallizable of immunoglobulin G (Fc-IgG), insulin, thyroglobulin, S100 protein, surface antigen of germ cell and prostate (Spr), thrombocyte membrane protein (TrM), antineutrophil cytoplasmic antibodies (ANCA), and membrane antigen of glomerular cells (KiMS). Venous blood sampling was carried out in the main group at the time of establishing FGR diagnosis (the third trimester of pregnancy in all cases): early manifested FGR – 29 [28; 31] weeks, late manifested FGR – 5 [33; 36] weeks, comparison group II – 33 [32; 35] weeks.Results. To diagnose early FGR, the level of the following autoimmune АВ was shown to be significantly increased against hCG, collagen, S100 protein, TrM, ANCA, KiMS (p = 0.037; р = 0.001; р = 0.013; р = 0.005; р = 0.003; p &lt; 0.001, respectively), whereas late FGR was diagnosed based on measuring АВ against DNA, collagen, insulin, S100 protein (p = 0.002; p = 0.003; p = 0.010; p &lt; 0.001, respectively).Conclusion. Detecting autoimmune antibodies has shown its informative importance in pregnant women with FGR, so that changes in serum autoantibody level may serve as a laboratory marker of early and late FGR.

Non-invasive prognostic markers of the risk of preterm rupture of the membranes in premature pregnancy

The objective: to study the prognostic significance of non-invasive markers of endogenous intoxication for determining the risk of premature rupture of membranes (PROM) at the gestation period of 26–34 weeks.Materials and methods. During the study the patients were divided into two groups: the 1st (main) group – 80 women with PROM at 26–34 weeks of pregnancy, and the 2nd (control) group – 50 women with a physiological course of pregnancy and term delivery without complications. The mean age of the examined women was 29.60±6.30 years. To determine the diagnostic value of the level of hematological indicators (concentration of leukocytes (WBC), granulocytes (GRAN), lymphocytes (LYM) in peripheral blood) and indices of endogenous intoxication (EI) as predictors of PROM and the initiation of preterm labor at a gestation period of 26–34 weeks, ROC-analysis was performed and the average quality of these prognostic factors was established (p&lt;0.001).Results. The optimal cut-off point (cut-off value) for predicting PROM in preterm pregnancy according to the criterion of the maximum balance between sensitivity and specificity corresponded to WBC was more than 12.39/l, LYM – less than 19 %, GRAN – more than 76 %, NLR – more than 3.87, Kalf-Kalif’s leukocyte intoxication index (LII) is more than 3.42, Ostrovsky’s LII – more than 2.76. It was established that the area under the curve (AUROC) was 0.786 for WBC, 0.863 for LYM, 0.847 for GRAN, 0.866 for NLR, 0.753 for LII Ostrovsky, which testifies to the significant prognostic value of the studied predictors. Conclusions. The main non-invasive markers of the degree of activity of the inflammatory process and the severity of endogenous intoxication in premature birth with PRPO in pregnant women are: the total number of leukocytes, the level of granulocytes and lymphocytes, Kalf-Kalif LII and the neutrophil-lymphocyte ratio. In order to detect infectious markers of intra-amniotic infection and the further development of PROM and premature birth, it is recommended to calculate the level of endogenous intoxication in the second half of pregnancy using general blood analysis data on a hemolytic analyzer (WBC, GRAN, LYM, NLR).

Features of immunohistochemical markers of stem CELLS CD-117, CD-44 in female placentas on the background of chronic stress

Background. Placenta is a subject of interest to a wide range of scientists because it is rich in stem cells and their precursors. A stem cell is a cell that has the ability to self-repair and can differentiate into offspring (daughter cells) of one or more germ layers. In recent years, scientists have obtained new data of stem cells regenerative potential. However, only isolated publications about placental stem cells are available. Therefore, our studies about placental stem cells are important for discovery of structural and molecular mechanisms, their changes under the influence of chronic stress.Objective: to study the features of immunohistochemical markers of pluripotent stem cells and their morphological features.Materials and methods. We examined 80 women placentas with chronic stress in comparison with control using general histological and immunohistochemical methods in the following groups: group 1 – women placentas with physiological course of pregnancy in term 38–40 weeks, group 2 – women placentas with miscarriage, group 3 – women placentas with chronic stress due to internal irradiation (4.5 Bq/kg and more), group 4 – women placentas which had COVID-19 during pregnancy.Results. There was a significant increase of stem cell markers expression in the three study groups with a significant predominance in groups 3 and 4. It was also determined the different direction of their active factors.Conclusions. The general changes of all structures of the placental barrier are detected as a result of chronic stress due to various factors: micro detachment of the decidual membrane (significant increase in cases in the studied groups); malperfusion in the structures of the maternal placental barrier; in the placenta stem cells of the three study groups in comparison with the control were found stress markers. Thus, chronic stress due to various factors causes the same type of changes in placental structures, but they have different degrees of expression – with internal irradiation doses ≥ 4.8 Bq/kg, these changes are most expressive.

Features of gestational period and perinatal outcomes in women with insulin resistance

Aim. To study the course of pregnancy and perinatal outcomes in women with insulin resistance. Material and methods. A retrospective and prospective study of 102 women and their newborns who were born in the State Institution “Research Institute of Obstetrics, Gynecology, and Perinatology” for the period 2017-2019 was conducted. All pregnant women were divided into 3 groups according to the level of insulin resistance index (NOMA index). Group I - 42 pregnant women with developmental risk factors for diabetes with an insulin resistance index above 2.84. Group II consisted of 30 subjects with a NOMA index below 2.21, and Group III (n = 30) consisted of healthy pregnant women with a physiological course of pregnancy and labor. Results. Newborns born to women with a NOMA index above 2.84 (pathological insulin resistance) have a high incidence of perinatal complications: central nervous system defects, various degrees of asphyxia, hypotrophy, and immaturity. Conclusion. Insulin resistance in general affects pregnancy and has a negative impact on the course of pregnancy, causing a high incidence of complications such as threatened miscarriage, preeclampsia, chronic placental insufficiency and affecting perinatal outcomes.