Obstetric Syndrome Research Articles

Reproductive effects of wartime stress and possibilities of their correction (Literature review)

The article presents modern literary data and data of own clinical observations regarding the effects of long-term chronic stress on reproductive processes with an emphasis on the effects of wartime. All stages of the reproductive cycle, from the regulation of the menstrual cycle, conception and implantation to the birth of a child, are energy-consuming and unprofitable for the body. All these processes require a lot of energy, but their purpose is to reproduce the species, not to maintain homeostasis. Therefore, the body temporarily slows down these processes, withdraws energy aimed at their support, and uses it to resist stress.The biological meaning of inhibition of reproductive function in stressful conditions is that if a woman becomes pregnant under unfavorable conditions, it is bad for her body, and for the offspring, and for the future prospects of the biological species as a whole. Therefore, from an evolutionary point of view, it is very beneficial to reduce the production of hormones, exclude ovulation and prevent implantation, and reduce libido during periods of high stress.Stress causes activation of the neuroendocrine and sympatho-adrenal systems, which leads to the release of such hormones as cortisol, adrenaline, norepinephrine into the blood. This helps to mobilize the body’s resources to overcome a threatening situation. However, prolonged stress depletes these systems and leads to maladjustment and increased risk of disease. Stress hormones affect all body systems, including the reproductive system. According to the literature, stress disorders occur three times more often in women than in men.In conditions of chronic stress, in particular during war, pregnancy complications can be caused by stress of various origins: metabolic, associated with micronutrient deficiency, psychological, physical, a combination of factors.Prenatal stress during wartime is a part of our existence, which reduces the quality of life of a pregnant woman and affects the intrauterine development of the fetus and the subsequent health of the child. Long-term chronic stress also leads to deterioration of the general state of health of the expectant mother: it reduces work capacity and appetite, causes lethargy, apathy, sleep disturbances, and increases the risk of obstetric complications.Stress negatively affects the state of immunity of the female population both before conception and during pregnancy, which can lead to the activation of latent infections, and makes the body of pregnant women more vulnerable to acute seasonal infections. This is also facilitated by the lack of necessary vitamins and trace elements with antioxidant properties in conditions of occupation, disruptions in the supply of medicines to certain problematic regions of the country, frequent changes of residence, etc.During pregnancy, all the negative effects of wartime can be realized in the form of major obstetric syndromes. In conditions of pronounced energy deficit caused by long-term stress, the body has to provide for itself to the detriment of the future child, which leads to ZRP, and in the most tragic cases – to intrauterine death. Violation of the psycho-emotional state of pregnant women today leads to the birth of “children of war” – insecure, low self-esteem, deeply ill babies with mental disorders.For the onset of pregnancy and its successful bearing, vitamins and micro/macroelements with antioxidant properties are needed in order to resist oxidant stress inherent in stressful conditions (vitamins of group B, vitamin D, iron, magnesium, omega-3 polyunsaturated fatty acids, L-arginine, L- carnitine). Rational management of pregnancy in today’s complex conditions should be complex and multi-vector. One of the promising directions in ensuring an uncomplicated course of pregnancy and successful perinatal outcomes is work with perinatal psychologists. At the same time, the use of additional psychosomatic effects of basic therapy should not be underestimated.

The level of pregnancy and childbirth complications among the residents of front-line city of Kharkiv

Background. The city of Kharkiv has been located in the area of armed conflict or the front-line zone since the beginning of the invasion of Russian troops. A part of the female reproductive-aged population constantly remains in Kharkiv which determines the possible negative impact of wartime stress. The purpose – of the work was to study the level of pregnancy and childbirth complications among women living in Kharkiv. Materials and Methods. A retrospective observational study was conducted based on the materials of the municipal non-commercial enterprise «Municipal Perinatal Center» of the Kharkiv City Council. All the examined contingent was divided into three groups. 2914 women who gave birth in 2021 were included in Group I. There were 956 patients in Group II whose pregnancies were completed in term via childbirth in 2022. Group III included 1288 women who gave birth in 2023. The study was conducted by studying the cards of pregnant women in the computer-automated system of the perinatal center Results. The level of thyroid diseases was likely to increase in 2022 compared to the prior level. In 2023, the upward trend continued. A probable increase in the incidence of diabetes mellitus in pregnant women in 2023 compared to the data of 2021 was detected. Interestingly, the level of anemia and cardiovascular diseases remained stable. However, a significant increase in the urinary system’s infectious processes was established in 2023 compared to previous years. Unfortunately, a substantial increase in the level of maternal trauma during childbirth has been established. This was especially true concern on vaginal and cervical tears. Therefore, sanitation of the urogenital system can be the key to reducing maternal trauma during childbirth. Conclusions. During the military operations, an increase in the level of medical complications among pregnant women in the city of Kharkiv was noted due to a rise in some endocrine diseases and urinary tract infections. The increase in the prevalence of vaginal infections has led to a rise in the rate of vaginal and perineal ruptures. This requires an emphasis on infection monitoring and timely sanitation of the birth canal. The use of preventive measures made it possible to keep the level of major obstetric syndromes such as premature births, and pre-eclampsia, as well as the level of childbirth complications quite stable. The established features should become the basis for further work in the direction of reducing the negative consequences of military aggression on the health of pregnant women in the city of Kharkiv.

Low-dose aspirin improves blood perfusion of obstetric anticardiolipin syndrome in China.

This study evaluates the endometrial receptivity of obstetric anticardiolipin syndrome (OAPS) patients using various ultrasound indicators and the efficacy of low-dose aspirin (LDA) treatment. This retrospective study recruited patients from Shanghai Ren Ji Hospital, China from January 2022 to December 2023. Doppler parameters of the endometrium and uterine artery blood flow were recorded to assess the endometrial receptivity of OAPS patients compared with normal pregnant women and an other immune diseases group. The receiver operating characteristic curve was used to predict the risk of OAPS patients. Doppler parameters of OAPS patients were conducted repeatedly after a 2-month period of treatment with LDA. Compared with normal pregnant women, the OAPS group showed remarkably increased endometrial perfusion resistance (PI, RI, S/D) and uterine artery perfusion resistance (RI and S/D) (P < 0.001) and had good predictive values (area under the curve = 0.806, 0.976, 0.942, 0.902, and 0.901, respectively). The endometrial thickness of the OAPS group was much thinner than that of the normal group (P < 0.001). Uterine blood flow impedance PI showed no difference in both groups (P = 0.68). In comparison to other autoimmune diseases, the OAPS group also showed an increasing trend in the resistance of endometrium and uterine artery blood flow. After LDA treatment, there was an obvious improvement in the endometrial blood flow perfusion in the OAPS group (P < 0.01). Compared with the normal group and other autoimmune diseases, the resistance of endometrial and uterine artery blood flow in the OAPS group was increased significantly. The Doppler index showed the predictive value of OAPS, and it was confirmed that LDA could enhance blood perfusion among OAPS women.

First-Trimester Preeclampsia-Induced Disturbance in Maternal Blood Serum Proteome: A Pilot Study.

Preeclampsia (PE) is a complex and multifaceted obstetric syndrome characterized by several distinct molecular subtypes. It complicates up to 5% of pregnancies and significantly contributes to maternal and newborn morbidity, thereby diminishing the long-term quality of life for affected women. Due to the widespread dissatisfaction with the effectiveness of existing approaches for assessing PE risk, there is a pressing need for ongoing research to identify newer, more accurate predictors. This study aimed to investigate early changes in the maternal serum proteome and associated signaling pathways. The levels of 125 maternal serum proteins at 11-13 weeks of gestation were quantified using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM MS) with the BAK-125 kit. Ten serum proteins emerged as potential early markers for PE: Apolipoprotein M (APOM), Complement C1q subcomponent subunit B (C1QB), Lysozyme (LYZ), Prothrombin (F2), Albumin (ALB), Zinc-alpha-2-glycoprotein (AZGP1), Tenascin-X (TNXB), Alpha-1-antitrypsin (SERPINA1), Attractin (ATRN), and Apolipoprotein A-IV (APOA4). Notably, nine of these proteins have previously been associated with PE in prior research, underscoring the consistency and reliability of our findings. These proteins play key roles in critical molecular processes, including complement and coagulation cascades, platelet activation, and insulin-like growth factor pathways. To improve the early prediction of PE, a highly effective Support Vector Machine (SVM) model was developed, analyzing 19 maternal serum proteins from the first trimester. This model achieved an area under the curve (AUC) of 0.91, with 87% sensitivity and 95% specificity, and a hazard ratio (HR) of 13.5 (4.6-40.8) with p < 0.001. These findings demonstrate that serum protein-based SVM models possess significantly higher predictive power compared to the routine first-trimester screening test, highlighting their superior utility in the early detection and risk stratification of PE.

Prevention of Pregnancy Complications Using a Multimodal Lifestyle, Screening, and Medical Model.

Prevention of pregnancy complications related to the "great obstetrical syndromes" (preeclampsia, fetal growth restriction, spontaneous preterm labor, and stillbirth) is a global research and clinical management priority. These syndromes share many common pathophysiological mechanisms that may contribute to altered placental development and function. The resulting adverse pregnancy outcomes are associated with increased maternal and perinatal morbidity and mortality and increased post-partum risk of cardiometabolic disease. Maternal nutritional and environmental factors are known to play a significant role in altering bidirectional communication between fetal-derived trophoblast cells and maternal decidual cells and contribute to abnormal placentation. As a result, lifestyle-based interventions have increasingly been recommended before, during, and after pregnancy, in order to reduce maternal and perinatal morbidity and mortality and decrease long-term risk. Antenatal screening strategies have been developed following extensive studies in diverse populations. Multivariate preeclampsia screening using a combination of maternal, biophysical, and serum biochemical markers is recommended at 11-14 weeks' gestation and can be performed at the same time as the first-trimester ultrasound and blood tests. Women identified as high-risk can be offered prophylactic low dose aspirin and monitored with angiogenic factor assessment from 22 weeks' gestation, in combination with clinical assessment, serum biochemistry, and ultrasound. Lifestyle factors can be reassessed during counseling related to antenatal screening interventions. The integration of lifestyle interventions, pregnancy screening, and medical management represents a conceptual advance in pregnancy care that has the potential to significantly reduce pregnancy complications and associated later life cardiometabolic adverse outcomes.

Biomarkers in the prediction of complications in pregnancy after assisted reproductive technology.

To compare the temporal changes in mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) across gestation between assisted reproductive technology (ART) pregnancies complicated with great obstetrical syndromes (GOS) or gestational diabetes (GDM) ± large-for-gestational-age (LGA) fetus, and uncomplicated ART pregnancies. This was a prospective longitudinal study of 143 women with singleton pregnancies who conceived through ART at the Department of Obstetrics and Gynecology, Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong SAR between December 2017 and January 2020. The participants were followed up at 6-6+3, 11-13+6, 20-24+6, 30-34+6, and 35-37+6 weeks for the measurement of MAP, UtA-PI, PlGF, and sFlt-1. A linear mixed-effects analysis was performed to compare the biomarkers in the GOS, GDM ± LGA, and uncomplicated groups across gestation. Thirty-three (23.1%) and fifty-five (31.5%) women were diagnosed with GOS and GDM ± LGA, respectively. The GOS group had higher estimated marginal mean log10 MAP mulitples of the median (MoM) across gestation, compared with the uncomplicated group (0.00771 vs -0.02022; P < 0.001), when adjusting for clinical visits and days of embryo transfer. The absolute mean log10 MAP MoM in the GOS group was found to be significantly higher than that of the uncomplicated group at all clinical visits from 6 weeks onwards. Furthermore, the estimated marginal mean log10 PlGF MoM was significantly lower in the GOS group across gestation, compared with the uncomplicated group (-0.04226 vs 0.05566; P = 0.010). The significant difference in log10 PlGF MoM was observed from 11-13+6 to 30-34+6 week of gestation (P < 0.05). However, no significant differences in the estimated marginal means of log10 UtA-PI MoM and log10 sFlt-1 MoM between GOS and uncomplicated groups were observed. GDM ± LGA group had a lower estimated marginal mean log10 PlGF MoM throughout pregnancy compared with the uncomplicated group (-0.01536 vs 0.05572; P = 0.032). In the individual visit analysis, the significant difference was observed at the 20-24+6 and 35-37+6 weeks visits (P < 0.05). There were no significant differences in estimated marginal mean log10 MoM of MAP, UtA-PI, and sFlt-1 between GDM ± LGA and uncomplicated groups during pregnancy. Our study has revealed that among pregnancies conceived through ART, GOS is associated with higher MAP and lower PlGF from early gestation until late third trimester, while GDM ± LGA is associated with lower PlGF during the second half of pregnancy. The same degree of differences in MAP and PlGF persists from early until late gestation in the GOS group and these findings highlight the importance of early screening during the first trimester to identify women who are at risk for developing GOS following ART procedures. Lastly, the potential of PlGF in predicting the development of GDM from the second trimester of pregnancy requires further investigation.

Методологія профілактики великих акушерських синдромів

Aim - to develop a method of prevention of major obstetric syndromes (MOS) from the standpoint of a single genesis determined by morphofunctional disorders in the fetoplacental system (FPS), with an assessment of effectiveness by methodological standards of evidence-based medicine Materials and methods. The group I - 32 pregnant women, prevention of MOS was carried out with low doses of acetylsalicylic acid (ASA) at 100-150 mg per os once a day, from 12 to 36 weeks of pregnancy; the group II - 31 pregnant women, who from 6 to 16 weeks were treated prophylactically with progesterone according to the scheme: 200 mg 1 time per day per vagina every day; the group III - 36 pregnant women who received prophylactic monotherapy, consisting of taking magnesium in combination with vitamin B6 for three courses of 6 weeks each; the group IV - 56 pregnant women who refused any preventive measures; the control group (CG) - 50 healthy pregnant women. Тhe effectiveness of prophylactic therapy was evaluated by dynamic examination of the pregnant groups of the study, which included the determination of the following indicators: placental alpha microglobulin (PAMG); placental growth factor; placental protein (PAPP-A), blood leukocyte elevation index, allergy index, concentration of magnesium in blood serum. To objectify the effectiveness of the developed method, the standards of evidence-based medicine were applied. Statistical processing of research results was carried out using standard Microsoft Excel 5.0 and Statistical 6.0 programs. Results. In pregnant women of the group IV, the level of the fibronectin (521±17 μg/ml) increased by an average of 17%, compared to patients of the groups I-III (355±12 μg/ml, 361±13 μg/ml, 368±16 μg/ml; p&lt;0.05), which led to a subsequent increase in the frequency of spontaneous premature births in patients of the group IV; the level of PAMG exceeds the value in the CG by 7.7 times in the group IV; in the group III by 1.7 times, and in pregnant women of groups I and II, it was 25.2±3.8 ng/ml and 26.4±4.2 ng/ml, respectively, against 177±18 ng/ml in group IV (p&lt;0.05). The concentration of the PAPP-A was reduced from the early stages of pregnancy in all studied groups - 6.9±1.8 mg/l, 8.8±1.9 mg/l, 9.2±2.1 mg/l, 7.5±1.6 mg/l (according to the groups I-IV) versus 15.7±2.5 mg/l in the CG (р&lt;0.05). When using the magnesium drug (III group), there are differences with the group IV in most indicators. Conclusions. Methods for the prevention of a complicated course in the high-risk groups for the development of vasculitis when studying personalized and predictive value, which made it possible to divide them in order from more effective to less effective: the method with the appointment of low doses of ASA was in the first place; on the II - prophylactic appointment of micronized vaginal progesterone; on the III - the use of magnesium. The research was conducted according to principles of Declaration of Helsinki. Protocol of research was proved by local ethical committee, mentioned in institution’s work. A informed sonsennt was collected in order to carry out the research. The author is stating no conflict of interests is declared.

Clinical effectiveness of prevention of great obstetrical syndromes

The objective: development of a method of prevention of great obstetrical syndromes (GOS) from the standpoint of a single genesis determined by morphofunctional disorders in the fetoplacental system (FPS) and evaluation of its clinical effectiveness.Materials and methods. 155 women of the high-risk group for the development of GOS were examined. I group – 32 pregnant women who had GOS prophylaxis with low doses of acetylsalicylic acid (ASA) 100–150 mg per os once a day from the 12th to the 36th week of pregnancy; II group – 31 pregnant women who from the 6th to the 16th week had prophylactically progesterone according to the scheme: 200 mg once a day per vaginally every day; III group – 36 pregnant women who received prophylactic monotherapy, consisting of the use of magnesium with a complex with vitamin B6 for three courses of 6 weeks each; IV group – 56 pregnant women who refused any preventive measures.To assess the effectiveness of preventive therapy a dynamic examination of the pregnant women of the study groups, their fetuses and newborns was carried out. Statistical processing of research results was carried out using standard Microsoft Excel 5.0 and Statistica 6.0 programs.Results. The analysis of obstetrical and perinatal outcomes in women of the high-risk group for the development of GOS showed that the development of placental insufficiency (PI) in the IV group was realized in 100% (56 cases), including severe forms in 51.8% (29 cases); the frequency of PI in I, II and III groups was 12.5% ​​(4 cases), 29.0% (9 cases) and 36.6% (11 cases), respectively, and was significantly lower (p&lt;0.05); premature births were in 3 cases each in I and III groups, which amounted to 9.3% and 8.3%, respectively (р&lt;0.05), in II group – 2 cases (6.5%); p&lt;0.05.In general, the realization of GOS (preeclampsia, fetal growth retardation syndrome, premature birth) in I group was 25.0% (8 cases), including severe form – 3.1% (1 case); in the II group – 29.0% (9 cases), severe forms – 2 cases (6.3%); in the III group – 30.6% (11 cases), severe forms – 3 cases (8.3%) versus 100.0% (56 cases) realization of all clinical manifestations of GOS in the IV group of the study (р&lt;0.05).Conclusions. A promising direction for the prevention of vasculitis in the high-risk group for their development is the consistent, early gestational appointment of low doses of ASA according to the developed method, which demonstrates the greatest effectiveness: a significant reduction in the frequency of preeclampsia, placental insufficiency with fetal growth retardation, premature birth, severe forms of preeclampsia according to optimized by the standards of evidence-based medicine: the number of pregnant women who need prophylaxis is 1.4; 95% confidence interval (CI): 1.1–1.7; odds ratio 5.3; 95% CI: 4.7–5.8.

The condition of newborns and the course of the early neonatal period in children from mothers who had complications from the group of great obstetric syndromes

The condition of newborns and the course of the early neonatal period in children from mothers who had complications from the group of great obstetric syndromes

New ideas about the maternal gut microbiome as a source of fetal programming

New genetic technologies that have emerged and been introduced into practice over the past 20 years, including 16s rRNA sequencing, have significantly expanded our understanding of the microbial composition of the human body. The gut is one of the most densely populated microbial niches in the human body. Numerous studies have shown the relationship of the gut microbiome with various non-communicable diseases, including diabetes mellitus, obesity, allergies and even mental disorders. The perinatal period, as one of the most hormonally dependent ones in human ontogenesis, has a direct impact on the composition of the intestinal microbiota, just as the microbiota itself can be a precursor and etiological cause of pregnancy complications. In this regard, the aim of this review article was to systematize data on the gut microbiota of the maternal body in normal and pathological pregnancy, as well as to analyze data on the interaction of the maternal gut microbiome with the fetal immune system. The review presents data on changes in the maternal intestinal microbiome in normal pregnancy, during infertility, as well as in pregnancy complicated with obesity, gestational diabetes mellitus and preeclampsia. The review also shows how the maternal microbiome is able to “educate” the fetal immune system in utero, thereby preparing the child, who develops in a sterile womb, for extrauterine life surrounded by a large number of various microorganisms. These mechanisms include the direct effect of not only the microorganisms themselves, but also, even largely, their metabolites — primarily short-chain fatty acids. All these presented data allow for concluding that the maternal microbiome is essentially a separate regulatory homeostatic system, along with the immune, endocrine and cardiovascular systems, which may determine the development of certain complications of pregnancy and shape the health of the unborn child. Interventions in the composition of the maternal gut microbiota may be a way to modulate the course of pregnancy and prevent major obstetric syndromes.

Implication of viruses in the etiology of preeclampsia.

Preeclampsia is one of the most common disorders that poses threat to both mothers and neonates and a major contributor to perinatal morbidity and mortality worldwide. Viral infection during pregnancy is not typically considered to cause preeclampsia; however, syndromic nature of preeclampsia etiology and the immunomodulatory effects of viral infections suggest that microbes could trigger a subset of preeclampsia. Notably, SARS-CoV-2 infection is associated with an increased risk of preeclampsia. Herein, we review the potential role of viral infections in this great obstetrical syndrome. According to in vitro and in vivo experimental studies, viral infections can cause preeclampsia by introducing poor placentation, syncytiotrophoblast stress, and/or maternal systemic inflammation, which are all known to play a critical role in the development of preeclampsia. Moreover, clinical and experimental investigations have suggested a link between several viruses and the onset of preeclampsia via multiple pathways. However, the results of experimental and clinical research are not always consistent. Therefore, future studies should investigate the causal link between viral infections and preeclampsia to elucidate the mechanism behind this relationship and the etiology of preeclampsia itself.

Імунологічні особливості у вагітних із великими акушерськими синдромами

Aim of the research – to evaluate the adaptive capabilities of the immunological system in pregnant women who had complications from the group of major obstetric syndromes (МОS) for the further development of an algorithm for the prevention of this complication. Materials and methods. The main study group (MG) - 99 pregnant women who had a complication from the group of MOS, which was clinically manifested by placental insufficiency (PI); control group (CG) - 50 practically healthy pregnant women with a healthy reproductive history and an uncomplicated course of this pregnancy. The number (x109/l) and relative (%) of lymphocyte subpopulations CD3+ (T-lymphocytes), CD4+ (helper-inducers), CD8+ (cytotoxic suppressors), CD56+ (natural killers), CD19+ (B-lymphocytes) were determined; the presence of antiphospholipid antibodies (APA); total hemolytic activity of the classical way of complement activation (CH50); levels of IgG, IgM, IgA. Statistical processing of research results was carried out using standard Microsoft Excel 5.0 and Statistical 6.0 programs. Results. In the I and II trimesters of pregnancy in MG and CG, a tendency to decrease was observed, СM4+ (51.8±2.5% and 48.9±1.6; 58.4±2.3% and 55.6±2.6%), and СD8+ (24.6±2.4% and 21.2±1.2%; 31.3±2.5% and 30.9±2.7%), which led to an increase in the immunoregulatory index (СD4+/СD8+) in MG (р&lt;0.05). The level of СD19+, during gestation there was an increase in their relative number in MG (13.6±0.98%; 16.4±2.03% and 21.1±2.01%) (p&lt;0.05); a predominance of the percentage of CD56+ lymphocytes, which have the properties of natural killers, was observed in pregnant MG (12.3±1.7%; 15.1±1.7%; 13.9±1.73% vs. 8.6±1.4%; 8.1±1.18%; 7.2±0.98%; p&lt;0.05). Hemolytic activity of the classical pathway of complement activation (CH50) in MG pregnant women was 1.5 times higher compared to CG pregnant women (p&lt;0.05). APA, represented by IgG to cardiolipin, were detected in 47 (47.5%) pregnant women MG and 4 (8.0%) women pregnant CG (p&lt;0.05). Conclusions. Іn pregnant women with МОS, there is an immune maladaptation that progressively increases in the dynamics of gestation and is manifested by excessive activation of natural killers (CD56+), an increase in the immunoregulatory coefficient (CD4+/CD8+), an increase in the percentage of B-lymphocytes (CD19+), dysimmunoglobulinemia, which is accompanied by high indicators of the general hemolytic activity of the classical pathway of complement activation (CH50), the presence of APA. The research was conducted according to principles of Declaration of Helsinki. Protocol of research was proved by local ethical committee, mentioned in institution’s work. A informed sonsennt was collected in order to carry out the research. The author is stating no conflict of interests is declared.

Особливості гормональної функції плаценти в жінок, які мали ускладнення з групи великих акушерських синдромів, що клінічно проявлялися плацентарною недостатністю

Purpose - to study the peculiarities of the hormonal function of the placenta during pregnancy in women who had complications from the group of major obstetric syndromes (MOS), clinically manifested by placental insufficiency, in order to further develop an algorithm for the prevention of this complication. Materials and methods. During the gestational process, the content of hormones: estradiol (E2), progesterone (PG), human chronic gonadotropin (hCG) and placental lactogen (PL) was determined in 99 pregnant women - the main group (MG) who had complications from the group of MOS, placental insufficiency (PI). The control group (CG) consisted of 50 practically healthy pregnant women with a healthy reproductive history and an uncomplicated course of this pregnancy, Statistical processing of research results was carried out using standard Microsoft Excel 5.0 and Statistica 6.0 programs. Results. During the entire gestational period, the level of E2, PL, hCG, and PG in pregnant women with MOS (MG) is significantly lower than in pregnant women with CG (p&lt;0.05). In the dynamics of the gestational process in MG patients, there is a significant lag in PG level indicators compared to indicators in CG: in 9-28 weeks - 46.4±4.24 nmol/l versus 162.6±22.10 nmol/l, respectively; p&lt;0.05 (3.5 times less), in 29-34 weeks - 128.9±6.80 nmol/l versus 294.2±34.62 nmol/l, respectively; p&lt;0.05 (2.3 times less), in 35-41 weeks - 148.2±2.26 nmol/l versus 434.6±56.70 nmol/l, respectively; p&lt;0.05 (2.9 times less). Conclusions. From the early stages of pregnancy, moderate hormonal dysfunction was detected in pregnant women with MOS in the form of a probable decrease in the levels of PL, PG, E2 and hCG compared to similar indicators in CG. In the future they have an unstable state of impaired placental hormonal function, which leads to the exhaustion of the adaptive reserves of the system mother-placenta-fetus in the form of a violation of the synthesis of key regulatory hormones responsible for the favorable course of gestation, the development and functioning of intrauterine life support systems. The research was conducted according to principles of Declaration of Helsinki. Protocol of research was proved by local ethical committee, mentioned in institution’s work. Women's informed consent was obtained for the study. No conflict of interests was declared by the author.

Placental TLR recognition of salivary and subgingival microbiota is associated with pregnancy complications

BackgroundPre-term birth, the leading cause of neonatal mortality, has been associated with maternal periodontal disease and the presence of oral pathogens in the placenta. However, the mechanisms that underpin this link are not known. This investigation aimed to identify the origins of placental microbiota and to interrogate the association between parturition complications and immune recognition of placental microbial motifs.61FbVQciH1C2BbwKYgvy28Video MethodsSaliva, plaque, serum, and placenta were collected during 130 full-term (FT), pre-term (PT), or pre-term complicated by pre-eclampsia (PTPE) deliveries and subjected to whole-genome shotgun sequencing. Real-time quantitative PCR was used to measure toll-like receptors (TLR) 1–10 expression in placental samples. Source tracking was employed to trace the origins of the placental microbiota.ResultsWe discovered 10,007 functionally annotated genes representing 420 taxa in the placenta that could not be attributed to contamination. Placental microbial composition was the biggest discriminator of pregnancy complications, outweighing hypertension, BMI, smoking, and maternal age. A machine-learning algorithm trained on this microbial dataset predicted PTPE and PT with error rates of 4.05% and 8.6% (taxonomy) and 6.21% and 7.38% (function). Logistic regression revealed 32% higher odds of parturition complication (95% CI 2.8%, 81%) for every IQR increase in the Shannon diversity index after adjusting for maternal smoking status, maternal age, and gravida. We also discovered distinct expression patterns of TLRs that detect RNA- and DNA-containing antigens in the three groups, with significant upregulation of TLR9, and concomitant downregulation of TLR7 in PTPE and PT groups, and dense correlation networks between microbial genes and these TLRs. 70–82% of placental microbiota were traced to serum and thence to the salivary and subgingival microbiomes. The oral and serum microbiomes of PTPE and PT groups displayed significant enrichment of genes encoding iron transport, exosome, adhesion, quorum sensing, lipopolysaccharide, biofilm, and steroid degradation.ConclusionsWithin the limits of cross-sectional analysis, we find evidence to suggest that oral bacteria might translocate to the placenta via serum and trigger immune signaling pathways capable of inducing placental vascular pathology. This might explain, in part, the higher incidence of obstetric syndromes in women with periodontal disease.

Placental differences between severe fetal growth restriction and hypertensive disorders of pregnancy requiring early preterm delivery: morphometric analysis of the villous tree supported by artificial intelligence

The great obstetrical syndromes of fetal growth restriction and hypertensive disorders of pregnancy can occur individually or be interrelated. Placental pathologic findings often overlap between these conditions, regardless of whether 1 or both diagnoses are present. Quantification of placental villous structures in each of these settings may identify distinct differences in developmental pathways. This study aimed to determine how the quantity and surface area of placental villi and vessels differ between severe, early-onset fetal growth restriction with absent or reversed umbilical artery Doppler indices and hypertensive disorders of pregnancy or the 2 conditions combined among subjects with disease severity that warrant early preterm delivery. We hypothesized that the trajectories of placental morphogenesis diverge after a common initiating insult of deep defective placentation. Specifically, we postulated that only villi are affected in pregnancy-related hypertension, whereas both villous and vascular structures are proportionally diminished in severe fetal growth restriction with no additional effect when hypertension is concomitantly present. In this retrospective cohort study, paraffin-embedded placental tissue was obtained from 4 groups, namely (1) patients with severe fetal growth restriction with absent or reversed umbilical artery end-diastolic velocities and hypertensive disorders of pregnancy, (2) patients with severe fetal growth restriction with absent or reversed umbilical artery Doppler indices and no hypertension, (3) gestational age-matched, appropriately grown pregnancies with hypertensive disease, and (4) gestational age-matched, appropriately grown pregnancies without hypertension. Dual immunohistochemistry for cytokeratin-7 (trophoblast) and CD34 (endothelial cells) was performed, followed by artificial intelligence-driven morphometric analyses. The number of villi, total villous area, number of fetoplacental vessels, and total vascular area across villi within a uniform region of interest were quantified. Quantitative analyses of placental structures were modeled using linear regression. Placentas from pregnancies complicated by hypertensive disorders of pregnancy exhibited significantly fewer stem villi (-282 stem villi; 95% confidence interval,-467 to-98; P<.01), a smaller stem villous area (-4.3 mm2; 95% confidence interval,-7.3 to-1.2; P<.01), and fewer stem villous vessels (-4967 stem villous vessels; 95% confidence interval,-8501 to-1433; P<.01) with no difference in the total vascular area. In contrast, placental abnormalities in cases with severe growth restriction were limited to terminal villi with global decreases in the number of villi (-873 terminal villi; 95% confidence interval,-1501 to-246; P<.01), the villous area (-1.5 mm2; 95% confidence interval,-2.7 to-0.4; P<.01), the number of blood vessels (-5165 terminal villous vessels; 95% confidence interval,-8201 to-2128; P<.01), and the vascular area (-0.6 mm2; 95% confidence interval,-1.1 to-0.1; P=.02). The combination of hypertension and growth restriction had no additional effect beyond the individual impact of each state. Pregnancies complicated by hypertensive disorders of pregnancy exhibited defects in the stem villi only, whereas placental abnormalities in severely growth restricted pregnancies with absent or reversed umbilical artery end-diastolic velocities were limited to the terminal villi. There were no significant statistical interactions in the combination of growth restriction and hypertension, suggesting that distinct pathophysiological pathways downstream of the initial insult of defective placentation are involved in each entity and do not synergize to lead to more severe pathologic consequences. Delineating mechanisms that underly the divergence in placental development after a common inciting event of defective deep placentation may shed light on new targets for prevention or treatment.

Exosomal small RNA profiling in first-trimester maternal blood explores early molecular pathways of preterm preeclampsia.

Preeclampsia (PE) is a severe obstetrical syndrome characterized by new-onset hypertension and proteinuria and it is often associated with fetal intrauterine growth restriction (IUGR). PE leads to long-term health complications, so early diagnosis would be crucial for timely prevention. There are multiple etiologies and subtypes of PE, and this heterogeneity has hindered accurate identification in the presymptomatic phase. Recent investigations have pointed to the potential role of small regulatory RNAs in PE, and these species, which travel in extracellular vesicles (EVs) in the circulation, have raised the possibility of non-invasive diagnostics. The aim of this study was to investigate the behavior of exosomal regulatory small RNAs in the most severe subtype of PE with IUGR. We isolated exosomal EVs from first-trimester peripheral blood plasma samples of women who later developed preterm PE with IUGR (n=6) and gestational age-matched healthy controls (n=14). The small RNA content of EVs and their differential expression were determined by next-generation sequencing and further validated by quantitative real-time PCR. We also applied the rigorous exceRpt bioinformatics pipeline for small RNA identification, followed by target verification and Gene Ontology analysis. Overall, >2700 small RNAs were identified in all samples and, of interest, the majority belonged to the RNA interference (RNAi) pathways. Among the RNAi species, 16 differentially expressed microRNAs were up-regulated in PE, whereas up-regulated and down-regulated members were equally found among the six identified Piwi-associated RNAs. Gene ontology analysis of the predicted small RNA targets showed enrichment of genes in pathways related to immune processes involved in decidualization, placentation and embryonic development, indicating that dysregulation of the induced small RNAs is connected to the impairment of immune pathways in preeclampsia development. Finally, the subsequent validation experiments revealed that the hsa_piR_016658 piRNA is a promising biomarker candidate for preterm PE associated with IUGR. Our rigorously designed study in a homogeneous group of patients unraveled small RNAs in circulating maternal exosomes that act on physiological pathways dysregulated in preterm PE with IUGR. Therefore, our small RNA hits are not only suitable biomarker candidates, but the revealed biological pathways may further inform us about the complex pathology of this severe PE subtype.

Obstetric echodynamics: Approaching a new field of multidisciplinary action

Maternal cardiovascular adaptation during pregnancy is essential for fetal development. Structural and functional changes, including increased blood volume, heart rate, and myocardial hypertrophy, are crucial for optimal tissue perfusion. Recent evidence supports viewing maternal and fetal cardiovascular systems as a unified functional unit, emphasizing the significance of hemodynamic evaluation in pregnancy. Some obstetrical syndromes result from maladaptive maternal cardiovascular responses. Non-invasive hemodynamic tests, like transthoracic echocardiography, aid in distinguishing phenotypes, guiding tailored management strategies for hypertensive disorders. Establishing obstetric hemodynamics as a multidisciplinary field, termed “Obstetric Echodynamics,” promises improved clinical care through standardized practices, interdisciplinary cooperation, and enhanced education.

Peculiarities of the morphology of the placenta of women with premature birth

The objective: аnalysis of the features of the morphological structure of the placenta of a woman who had complications from the group of main obstetric syndromes, which clinically constantly occur with previous defects. Materials and methods. The research was conducted according to the principles of the Declaration of Helsinki. The protocol of research was proved by the local ethical committee, mentioned in the institution’s work. An informed sonnet was collected to carry out the research. The study of the features of the morphological structure of the placenta of women was carried out - the main group (OG) of n=28 pregnant women with spontaneous preterm birth (PB) at a gestation period of 24-36 weeks and 6 days. The control group (CG) consisted of 20 placentas of practically healthy pregnant women with a healthy reproductive history and an uncomplicated course of this pregnancy. Statistical processing of research results was carried out using standard Microsoft Excel 5.0 and Statistica 6.0 programs. Results. The presence of inflammatory diseases of the lower parts of the reproductive system and urinary tract in pregnant women contributes to the development of membranitis (rs=0.42 and rs=0.31 respectively; p&lt;0.05) and omphalovasculitis (rs=0.45 and rs=0,35 respectively; р&lt;0.05). Fetal development delay syndrome is associated with the presence of involutive-dystrophic changes in the litter and dissociation of villi (rs=0.37 and rs=0.51 respectively; р&lt;0.05). At the same time, there are no compensatory-adaptive reactions and pronounced involutional-dystrophic changes and signs of villous maturation disorder in the placentas. An increase in the duration of the waterless interval is associated with the development of membranitis, omphalovasculitis, and pneumonia in the newborn (rs=0.36, rs=0.41, rs=0.57 respectively; p&lt;0.05). During the morphological examination of the placentas, inflammatory changes of varying severity were observed in all placentas. Omphalovasculitis was statistically significantly more frequent(p=0.04) in women with PB and in all cases was combined with the presence of membranes. The presence in the placenta of membraneous, omphalovasculitis and the presence of involutional dystrophic changes is associated with the development of clinical manifestations of chorioamnionitis and pneumonia in a newborn (rs=0.53, rs=0.52, and rs=0.40, respectively; p&lt;0.05). In the placentas of women with PB, compensatory and adaptive reactions are statistically significantly less frequent (p=0.00001) and involutive-dystrophic changes (p=0.00001), blood circulation disorders (p=0.0009) and villi dissociation are statistically significantly more frequent; р=0.02). Conclusions. Feature of the morphological structure of the placenta in women with premature birth is the frequent detection of inflammatory changes, signs of villous maturation disorders and involutional-dystrophic changes, and the absence of compensatory and adaptive reactions.

A mitochondrial regulator protein, MNRR1, is elevated in the maternal blood of women with preeclampsia

Objective Preeclampsia, one of the most serious obstetric complications, is a heterogenous disorder resulting from different pathologic processes. However, placental oxidative stress and an anti-angiogenic state play a crucial role. Mitochondria are a major source of cellular reactive oxygen species. Abnormalities in mitochondrial structures, proteins, and functions have been observed in the placentae of patients with preeclampsia, thus mitochondrial dysfunction has been implicated in the mechanism of the disease. Mitochondrial nuclear retrograde regulator 1 (MNRR1) is a newly characterized bi-organellar protein with pleiotropic functions. In the mitochondria, this protein regulates cytochrome c oxidase activity and reactive oxygen species production, whereas in the nucleus, it regulates the transcription of a number of genes including response to tissue hypoxia and inflammatory signals. Since MNRR1 expression changes in response to hypoxia and to an inflammatory signal, MNRR1 could be a part of mitochondrial dysfunction and involved in the pathologic process of preeclampsia. This study aimed to determine whether the plasma MNRR1 concentration of women with preeclampsia differed from that of normal pregnant women. Methods This retrospective case–control study included 97 women with preeclampsia, stratified by gestational age at delivery into early (<34 weeks, n = 40) and late (≥34 weeks, n = 57) preeclampsia and by the presence or absence of placental lesions consistent with maternal vascular malperfusion (MVM), the histologic counterpart of an anti-angiogenic state. Women with an uncomplicated pregnancy at various gestational ages who delivered at term served as controls (n = 80) and were further stratified into early (n = 25) and late (n = 55) controls according to gestational age at venipuncture. Maternal plasma MNRR1 concentrations were determined by an enzyme-linked immunosorbent assay. Results 1) Women with preeclampsia at the time of diagnosis (either early or late disease) had a significantly higher median (interquartile range, IQR) plasma MNRR1 concentration than the controls [early preeclampsia: 1632 (924–2926) pg/mL vs. 630 (448–4002) pg/mL, p = .026, and late preeclampsia: 1833 (1441–5534) pg/mL vs. 910 (526–6178) pg/mL, p = .021]. Among women with early preeclampsia, those with MVM lesions in the placenta had the highest median (IQR) plasma MNRR1 concentration among the three groups [with MVM: 2066 (1070–3188) pg/mL vs. without MVM: 888 (812–1781) pg/mL, p = .03; and with MVM vs. control: 630 (448–4002) pg/mL, p = .04]. There was no significant difference in the median plasma MNRR1 concentration between women with early preeclampsia without MVM lesions and those with an uncomplicated pregnancy (p = .3). By contrast, women with late preeclampsia, regardless of MVM lesions, had a significantly higher median (IQR) plasma MNRR1 concentration than women in the control group [with MVM: 1609 (1392–3135) pg/mL vs. control: 910 (526–6178), p = .045; and without MVM: 2023 (1578–8936) pg/mL vs. control, p = .01]. Conclusions MNRR1, a mitochondrial regulator protein, is elevated in the maternal plasma of women with preeclampsia (both early and late) at the time of diagnosis. These findings may reflect some degree of mitochondrial dysfunction, intravascular inflammation, or other unknown pathologic processes that characterize this obstetrical syndrome.

АКУШЕРСКИЙ ГЕМОЛИТИКО-УРЕМИЧЕСКИЙ СИНДРОМ, АССОЦИИРОВАННЫЙ С БЕРЕМЕННОСТЬЮ, У ПАЦИЕНТКИ С ИНФЕКЦИЕЙ И МАССИВНЫМ КРОВОТЕЧЕНИЕМ: КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ

The study aims to present a clinical case of a rare pathology such as obstetric hemolytic uremic syndrome associated with infection during pregnancy, and complicated by massive bleeding, a critical obstetric condition, and a high risk of maternal mortality in a near-miss case. The study analyzes changes in causes of maternal mortality rate in the Russian Federation, including changes towards extragenital diseases; indirect causes and embolisms; preeclampsia, obstetric bleeding, and sepsis despite their decrease in the causes of maternal mortality rate; and such diseases as thrombotic microangiopathy, which is considered a probable life-threatening maternal condition and named a critical obstetric condition, that can be diagnosed in a highinformation laboratory with an instrumental basis. Thrombotic microangiopathy is attributed to many diseases, therefore, there are many unclear and controversial issues in diagnosing such a disease during pregnancy. Its clinical symptoms include hemolytic microangiopathic anemia, thrombocytopenia, thrombosis of the terminal arterioles and capillaries of the microvascular bed, and multiple organ dysfunction.