BACKGROUND: Early-onset preeclampsia in multifetal pregnancy is a major clinical challenge associated with high maternal and perinatal morbidity and mortality. Its pathogenesis is complex and is thought to arise from interactions between genetic susceptibility and environmental factors, with oxidative stress representing a key mechanistic component. Although the genetic basis of oxidative stress has been investigated in a number of domestic and international research centers, comprehensive studies that integrate the epistatic interactions between genes and their relationship to oxidative status in patients with multifetal pregnancy remain scarce. AIM: The aim of this study was to assess the frequency of polymorphic variants in genes involved in hemostasis and folate metabolism, identify significant epistatic interactions, and evaluate oxidative status markers in patients with multifetal pregnancy complicated by early-onset preeclampsia. METHODS: This single-center case-control study included patients with multifetal pregnancy, with or without preeclampsia. Genotyping of 12 single nucleotide variants in hemostasis related genes (F2, F5, F7, F13, FGB, ITGA2, ITGB3, SERPINE1) and folate cycle genes (MTHFR, MTRR, MTR) was performed using real-time polymerase chain reaction. Oxidative status was assessed by total antioxidant capacity, lipid peroxidation index (PerOx), and the integral oxidative stress index (OxyStat). Epistasis was explored using the generalized multifactor dimensionality reduction (GMDR) method. RESULTS: The study included 157 women (main group: 38 women with early-onset preeclampsia; control group: 119 women without preeclampsia). The carriage of minor alleles in the SERPINE1 −6755G4G, ITGA2 807CT, and MTRR 66AG gene variants was associated with an increased risk of early-onset preeclampsia in multifetal pregnancy. The GMDR method identified significant epistatic interactions; the most predictive three-locus model (ITGA2 + SERPINE1 + MTRR genes) achieved a balanced accuracy of 0.8902 with a sensitivity of 97.5%. Patients with preeclampsia exhibited a marked oxidative imbalance, with a 4.2-fold decrease in total antioxidant capacity and nearly 3-fold increases in PerOx and OxyStat compared to control values. The carriage of the SERPINE1 4G allele and the ITGA2 T allele was associated with more pronounced impairment of oxidative status. CONCLUSION: The data obtained support a plausible pathogenic link between genetic susceptibility and oxidative stress in early-onset preeclampsia in multifetal pregnancy. Unfavorable genotype combinations in the SERPINE1, ITGA2, and MTRR genes may confer a high genetic risk that, in the context of multifetal gestation, is realized through hypercoagulability, endothelial dysfunction, and placental ischemia-reperfusion, culminating in severe oxidative stress and clinical manifestation of preeclampsia. The results substantiate the rationale for a comprehensive risk stratification approach integrating genetic testing and oxidative status assessment.

The article is republished in order to expand the audience. The article was published earlier in the Akusherstvo i Ginekologiya (Russian Federation): Sukhikh GT, Serov VN, Artymuk NV, Andreeva MD, Bazina MI, Baranov II, Bashmakova NV, Bezhenar VF, Belotserkovtseva LD, Geppe NA, Dolgushina NV, Zaretskaya NV, Zakharova IN, Zubkov VV, Enkova EV, Yesayan RM, Katkova NYu, Kvashnina EV, Kogan IYu, Korsak VS, Krasnopolskaya KV, Kukarskaya II, Molchanova IV, Nazarenko TA, Pestova TI, Podzolkova NM, Saveljeva IV, Sazonova AI, Semenov YuA, Tapilskaya NI, Tetruashvili NK, Tiselko AV, Fadeev VV, Shamugia NL, Shakhova MA, Shikh EV, Yarmolinskaya MI. The safety of hormone therapy during pregnancy. Joint statement by experts in reproductive medicine, obstetrics and gynecology, endocrinology, clinical pharmacology, neonatology and pediatrics Akusherstvo i Ginekologiya (Russian Federation). 2024;(8):196–206. (In Russ.) https://doi.org/10.18565/aig.2024.201.

Цель работы – изучить влияние фетоплацентарной недостаточности у беременных женщин на фоне внутриутробного инфицирования на состояние новорожденных и частоту выявления заболеваний различных органов и систем у детей раннего возраста (до трех лет). Методика. Проведено морфологическое и гистологическое исследование последов у 205 беременных женщин высокой группы инфекционного риска. Оценивали наличие признаков восходящего, гематогенного и смешанного инфицирования последа, а также признаки острой и хронической плацентарной недостаточности. В первом и втором триместрах беремен ности в сыворотке крови женщин методом иммуноферментного анализа определяли концентрацию кортизола, интерлей кина-6 (ИЛ-6) и интерлейкина-10 (ИЛ-10). Проводили анализ историй новорожденных с целью изучения частоты встречае мости заболеваний или состояний. Риски неонатальной патологии рассчитывали по методике Глуховца Б.И. Частоту выяв ления заболеваний различных органов и систем у детей до 3 лет устанавливали на основании анализа данных учетных форм № 025/у (медицинская карта пациента, получающего медицинскую помощь в амбулаторных условиях). Результаты. В группах с восходящим, гематогенным и смешанным инфицированием уровень кортизола в 1 триместре беременности был статистически значимо выше относительно группы контроля (р <0,05). Высокие показатели кортизола в этих же группах сохранялись и во II триместре беременности. Концентрация ИЛ-10 в группах с восходящим и гематоген ным инфицированием в сроке 11-12 недель беременности статистически значимо снижена. Обнаружена обратная корре ляционная связь между уровнем кортизола и уровнем ИЛ-10 при восходящем и гематогенном инфицировании. У женщин с признаками инфицирования последа чаще встречались незрелые промежуточные ворсины, которые свидетельствует о нарушении созревания плаценты. При восходящем инфицировании последа статистически значимо чаще развивалась хроническая компенсированная недостаточность, а при смешанном инфицировании – в стадии субкомпенсации. Гипо трофия плода статистически значимо чаще встречалась при гематогенном инфицировании. Частота выявления анализи руемых групп заболеваний у детей при внутриутробном инфицировании была статистически значимо выше в сравнении с контролем. Заключение. Полученные данные свидетельствуют о нарушении формирования фетоплацентарного комплекса при вос ходящем, гематогенном и смешанном путях инфицирования в связи с активацией продукции кортизола и снижении кон центрации ИЛ-10 в начале гестации. Формирование ранней фетоплацентарной недостаточности на фоне внутриутроб ного инфицирования плода является дополнительным фактором риска для здоровья новорожденных и детей первых лет жизни и требует тщательного наблюдения за состоянием их здоровья. The aim of the work is to study the effect of fetoplacental insufficiency in pregnant women against the background of intrauter ine infection on the condition of newborns and the frequency of detection of diseases of various organs and systems in young children (up to three years old). Methods. Morphological and histological examination of the afterbirth was performed in 205 pregnant women of a high infec tious risk group. The presence of signs of ascending, hematogenous and mixed infection of the afterbirth, as well as signs of acute and chronic placental insufficiency, were evaluated. In the first and second trimesters of pregnancy, the concentration of cortisol, interleukin-6 (IL-6) and interleukin-10 (IL-10) was determined in the blood serum of women by enzyme immunoassay. The histo ries of newborns were analyzed in order to study the frequency of diseases or conditions. The risks of neonatal pathology were calculated using the Glukhovets B.I. method. The frequency of detection of diseases of various organs and systems in children under 3 years of age was established based on the analysis of data from registration forms No. 025/y (medical card of a patient receiving medical care on an outpatient basis). Results. In the groups with ascending, hematogenous and mixed infection, cortisol levels in the 1st trimester of pregnancy were statistically significantly higher relative to the control group (p<0.05). High cortisol levels in the same groups persisted in the second trimester of pregnancy. The concentration of IL-10 in groups with ascending and hematogenous infection at 11-12 weeks of pregnancy was statistically significantly reduced. An inverse correlation was found between cortisol levels and IL-10 levels in ascending and hematogenous infections. In women with signs of infection of the placenta, immature intermediate villi were more common, which indicates a violation of the maturation of the placenta. With ascending infection of the afterbirth, chronic com pensated insufficiency developed statistically significantly more often, and with mixed infection – in the subcompensation stage. Fetal hypotrophy was statistically significantly more common in hematogenous infection. The frequency of detection of the ana lyzed groups of diseases in children with intrauterine infection was statistically significantly higher in comparison with the control. Conclusion. The data obtained indicate a violation of the formation of the fetoplacental complex in ascending, hematogenous and mixed infection pathways due to activation of cortisol production and a decrease in IL-10 concentration at the beginning of gestation. The formation of early fetoplacental insufficiency against the background of intrauterine infection of the fetus is an addi tional risk factor for the health of newborns and children in the first years of life and requires careful monitoring of their health.

Background Potocki-Lupski syndrome (PTLS, OMIM # 610883) is a rare genetic developmental disorder resulting from a partial heterozygous microduplication at chromosome 17p11.2. The condition is characterized by a wide variability of clinical expression, which can make its clinical and molecular diagnosis challenging. Case presentation We report here a family (mother and her two children) diagnosed with PTLS. When examining children, neurological and psychological (neuropsychiatric) manifestations (speech delay, mild mental retardation), motor disorders, craniofacial dysmorphism (microcephaly, dolichocephaly, triangular face, wide bulging forehead, long chin, antimongoloid slant, "elfin" ears) were revealed. The suspected clinical diagnosis was confirmed by MLPA and CMA molecular genetic testing which revealed the presence of a segmental aneusomy; microduplication in the 17p11.2 region. Conclusions Children with PTLS can have a clinically recognizable and specific phenotype: craniofacial dysmorphism, motor and neurological manifestations, which may implicate a possible genetic disease to the attending physician. Moreover, each child with this syndrome is unique and may have a different clinical picture. The management of such patients requires a multidisciplinary team approach, including medical genetic counseling.

Successful reproduction in mammals requires gamete development, fertilization, and early embryonic development. Defects in any of these processes can lead to infertility, recurrent miscarriages, and congenital defects. The clinical recognition of the genetic causes of female reproductive insufficiency using increasingly advanced genetic technologies poses a serious challenge for reproductive medicine in the 21st century. Herein, the current literature on genetic factors involved in reproductive losses was summarized. A literature search was conducted using Web of Science, MEDLINE, and PubMed databases for articles written in English on the genetic causes of women’s reproductive health disorders. Future implementation of whole-exome and whole-genome sequencing is expected to identify numerous genetic factors responsible for oocyte quality. Which will aid in increasing the likelihood of successful female reproductive function, improve the outcomes of assisted reproductive technologies, optimize treatment, and facilitate genetic diagnosis of patients.

Актуальность. Плацента является связующим звеном между матерью и плодом. Нормальное функционирование плаценты имеет важное значение для здоровья плода, а существенные изменения этой структуры могут быть связаны с развитием хронических заболеваний у потомства в будущем. Инфекционные агенты приводят к формированию дисфункции плаценты. Изучение влияния плацентарной дисфункции на плод и новорожденного приобретает растущий интерес в неонатальных исследованиях. Результаты патоморфологического исследования плаценты могут служить биомаркёрами внутриутробной патологии. Цель исследования – изучение влияния различных путей внутриутробного инфицирования плода на состояние центральной нервной системы (ЦНС) в неонатальном периоде и у детей раннего возраста. Материалы и методы. Проведено патоморфологическое исследование последа у 205 женщин. В зависимости от пути инфицирования, были выделены группы: восходящего инфицирования (n = 69), гематогенного (n = 33), смешанного (n = 44). Контрольная группа – 59 женщин без инфекционного поражения. Стандартной методикой проведено патологоанатомическое исследование последа. Оценивали состояние новорожденных, в крови пуповины подсчитывали лейкоциты. Оценивали состояние ЦНС детей в неонатальном периоде и раннем возрасте по данным формы N 025/у. Проанализировано 69 карт детей, из них 14 – контрольной группы, 21 карта – восходящего, 15 – гематогенного, 19 – смешанного инфицирования. Результаты. При инфицировании плаценты частота перинатальных поражений ЦНС возрастает от восходящего к смешанному пути (33,3%; и 79,0%; р < 0,01). Как в неонатальном периоде при внутриутробном инфицировании, так и в последующие три года жизни ребенка сохраняется высокая частота нарушений со стороны нервной системы. При восходящем инфицировании отношение шансов (ОШ) составляет 4,06 (0,42 – 39,25), при гематогенном ОШ=8,67 (0,88 – 84,83), при смешанном ОШ=22,28 (2,37 – 208,79). Клинически это проявляется задержкой психомоторного развития, нарушением психоречевого развития, вегетативными дисфункциями. Заключение. Гематогенное и смешанное инфицирование фетоплацентарного комплекса приводит к перинатальным поражениям ЦНС у детей. Наиболее выраженные сдвиги поражения ЦНС наблюдались при смешанном пути инфицирования. Патоморфологическая характеристика плаценты с расчетом рисков неонатальной патологии имеет высокую диагностическую значимость в предикции развития перинатальных поражений ЦНС. Background. The placenta is the environment for fetal development, it is the link between the mother and the fetus. The normal functioning of the placenta is important for fetal health, and significant changes in this structure may be associated with the development of chronic diseases in the offspring in the future. Infectious agents lead to the formation of placental dysfunction. The study of the effect of placental dysfunction on the fetus and newborn is gaining growing interest in neonatal research. The results of pathomorphological examination of the placenta can serve as biomarkers of intrauterine pathology. The aim of the study was to study the effect of various ways of intrauterine infection of the fetus on the state of the central nervous system (CNS) in the neonatal period and in young children. Materials and methods. A pathomorphological examination of the afterbirth was performed in 205 women. Depending on the path of infection, groups were identified: ascending infection (n = 69), hematogenic (n = 33), mixed (n = 44). The control group consisted of 59 women without an infectious lesion. A pathological examination of the afterbirth was performed using a standard technique. The condition of newborns was assessed, white blood cells were counted in the umbilical cord blood. The condition of the central nervous system of children in the neonatal period and early age was assessed according to the data of form N 025/y. 69 maps of children were analyzed, 14 of them from the control group, 21 from ascending, 15 from hematogenic, and 19 from mixed infection. Results. With infection of the placenta, the frequency of perinatal CNS lesions increases from an ascending to a mixed pathway and is statistically significant (33,3%; 79,0%; р < 0,01). Both in the neonatal period with intrauterine infection and in the next three years of a child’s life, a high frequency of disorders of the nervous system persists. With ascending infection, the OR is 4.06 (0.42 – 39.25), with hematogenous infection, OR = 8.67 (0.88 – 84.83), with mixed infection, OR = 22.28 (2.37 – 208.79). Clinically, this was manifested by delayed psychomotor development, impaired psychorechological development, and autonomic dysfunctions. Conclusion. Hematogenous and mixed infection of the fetoplacental complex leads to perinatal CNS lesions in children. The most pronounced shifts in CNS damage were observed with a mixed infection pathway. The pathomorphological characteristics of the placenta with the calculation of the risks of neonatal pathology have a high diagnostic significance in predicting the development of perinatal lesions of the central nervous system.

The study aims to compare the outcomes of 160 labor cases and their infants born at gestational age from 37 + 0 to 42 + 0 weeks prior and following the implementation of fetal scalp testing into gynecological practice as an additional method to diagnose fetal hypoxia. The examination included a retrospective study of 80 women in labor and 80 newborns before the scalp test, and a prospective study of another 80 women in labor and 80 newborns after the test. The results of the study demonstrated a reduced number of instrumental deliveries and an improvement in the state and outcomes of newborns with severe asphyxia by the first postnatal year. After intranatal lactate blood sampling in the early neonatal period, newborns with severe asphyxia demonstrated a significantly reduced rate of pathological pattern when their amplitude-integrated electroencephalography was recorded, and their hypoxic-ischemic encephalopathy was lower as well. In 24 months of observation, there were no statistically significant neurological complications in most of the children with severe asphyxia.

Introduction The problem of iron deficiency anemia (IDA), especially in pregnant women, continues to be relevant. Despite the achieved methods of diagnosis and treatment, the number of pregnant women with IDA continues to grow. Thus, according to WHO 2020 data, the prevalence of anemia among women of reproductive age ranged from 9.1 % in Australia to 69.6 % in Yemen. The aim of the work was to determination of the current state of the problem of IDA in pregnant women. Materials and methods Original articles, randomized clinical trials, and meta-analyses were reviewed in the Scopus database, PubMed and the eLibrary platform, using the key words “iron”, “oral”, “intravenous iron”, “intravenous iron therapy”, “pregnancy”, “anemia”, “treatment”, “randomized control trial”, “anemia in pregnancy”, “treatment of anemia in pregnancy”, “intravenous iron in pregnancy”, “IDA complications for mother and fetus”. The depth of the search was 5 years. Results and discussion There are different views on the classification and diagnosis of IDA in the guidelines of professional organizations. According to most guidelines hemoglobin and ferritin levels are the most reliable tests for the verification and prediction of IDA. Despite the fact that the peculiarities of the pathogenesis and approaches to the treatment of IDA have been studied, its prevalence among women remains very high. The reasons for this lie in inadequate diagnosis and incomplete therapy in terms of its duration and drugs selection. The methods of diagnosis and treatment of IDA are currently being actively studied and improved in anticipation of obtaining the greatest benefits. Conclusion Complications of IDA in the third trimester for newborns are the development of anemia, impaired development of the nervous system and cognitive disorders, which requires active prevention in the second trimester using, among other things, parenteral iron preparations.

The study aims to evaluate risk factors for complicated pregnancy courses based on the retrospective analysis of 510 anamneses from 2014 to 2021, as well as singleton and multiple pregnancies outcomes with and without preeclampsia registered in the Surgut District Clinical Center for Maternal and Child Health. The study states that chronic arterial hypertension, obesity, hypothyroidism, and preeclampsia in anamnesis may result in preeclampsia in singleton pregnancy, while its manifestation is associated with the worst neonatal outcomes and a more apparent multiple organ dysfunction syndrome. In multiple pregnancy, assisted reproductive techniques were a significant risk factor for preeclampsia. However, the pathological process demonstrated a moderate type of early preeclampsia and was not associated with unfavorable perinatal outcomes.

The study aims to generalize and systematize modern instrumental methods for assessing the fetus conditions during labor based on the scientific literature from the Web of Science, Medline, PubMed, and RISC. It was found that combination of the main and additional methods for assessing the fetus conditions during labor improves significantly the diagnosis of fetal hypoxia, while the blood analysis from the fetus scalp is an efficient additional diagnosing method for fetal hypoxia during labor.

The study aims to generalize and systematize information obtained from the literature of 10 years from the MEDLINE, PubMed, eLIBRARY.RU, and RISC databases about additional markers of glycemic control in gestational diabetes mellitus for evaluation of its effectiveness and treatment correction. The review article included 22 literature sources out of 156 analyzed publications on the issue. There is not enough research available on such markers as fructosamine, glycated albumin, and 1.5-anhydroglucitol. Therefore, it is required to study and implement them into practice further on in order to optimize the treatment and manage pregnancies with gestational diabetes mellitus.

The study aims to assess the risks for preeclampsia progression in pregnant women with SARS-CoV-2 based on the study obtained in 2021, which included the pregnancy course and outcome of 1 122 women divided into three groups. The groups were as following: 52 pregnant women with positive SARS-CoV-2 and preeclampsia, 302 women with negative SARS-CoV-2 and preeclampsia, and 768 pregnant women with positive SARS-CoV-2 and without preeclampsia. Chronic arterial hypertension prevailed in women with positive SARS-CoV-2 and preeclampsia by 2.5 times in comparison with those with negative SARS-CoV-2 and preeclampsia, and by 10.4 times in comparison with those with positive SARS-CoV-2 and without preeclampsia. Assisted reproductive technologies were used for pregnant women with positive SARS-CoV-2 and preeclampsia 7.9 and 11.8 times more frequently than for other groups of women. Women with preeclampsia suffered from premature birth, premature detachment of the placenta, cesarean delivery, and asphyxia of newborns at a higher rate.

BACKGROUND:Recurrent pregnancy loss is a serious clinical problem that complicates about 2% of pregnancies. There is evidence that thrombophilia and disorders of folate-methionine metabolism may cause recurrent pregnancy loss. AIM:The aim of this study was to evaluate the contribution of polymorphic variants of the genes of the hemostasis system and the folate-methionine cycle in women with recurrent pregnancy loss. MATERIALS AND METHODS:Clinical examination of 406 pregnant women divided into two study groups was carried out. The main study group consisted of 206 women with two or more pregnancy losses known up to 12 weeks of pregnancy; the control group included 200 apparently healthy women with a known history of two or more live births, no spontaneous or induced abortions, infertility, or endometriosis. All patients underwent a molecular genetic study of 12 single nucleotide polymorphisms in the genes of the hemostasis system and the folate-methionine cycle performed by real-time polymerase chain reaction. RESULTS:We studied single nucleotide polymorphisms in eight genes involved in the hemostasis system and in four genes of the folate-methionine cycle. An association of presence of alternative variants such as 1565C (rs5918) of theITGB3integrin beta-3 gene and A66G (rs1801394) of theMTRRmethionine synthase reductase gene with the development of recurrent pregnancy loss was found. The frequency of their occurrence was 29.1 and 77.7% in the recurrent pregnancy loss group vs. 12.0 and 49.0% in the control group, respectively (p 0.01). The combined carriage of the alternative variants 1565C (rs5918) of theITGB3gene and A66G (rs1801394) of theMTRRgene in the recurrent pregnancy loss group was diagnosed more often than in the control group and amounted to 47 (22.8%) vs. 12 (6.0%) cases ( = 5.047;p 0.01; odds ratio 3.631; 95% confidence interval 2.3749.034). We have thus developed a three-locus model of the synergetic action of allelic variants of the above genes in the development of recurrent pregnancy loss in early pregnancy [10976 GA (rs6046) of theF7, 455 GA (rs1800790) of theFGB, 1565 TC (rs5918) of theITGB3] with reproducibility of 8/10, sensitivity of 65.6%, and specificity of 68.8% ( = 15.7415,p 0.0001; odds ratio 3.341, 95% confidence interval 1.8246.118). CONCLUSIONS:This study allows for confirming the hypothesis that the status of genetic variants of theITGB3andMTRRgenes and the association of three single nucleotide polymorphisms: rs6046 of theF7, rs1800790 of theFGB, and rs5918 of theITGB3may be used as predictors of recurrent pregnancy loss development.

Одной из главных причин патологического течения беременности и родов выступает внутриутробная инфекционная патология. Трансплацентарное инфицирование плода считается одной из наиболее вероятных причин врождённых пороков развития, что создает медицинские и социальные проблемы. Клиническая картина внутриутробной инфекции во время беременности не всегда имеет специфические черты, что затрудняет её диагностику. Передача инфекционного возбудителя во время беременности от матери к плоду во многом зависит от функционирования иммунной системы женщины. Основными путями проникновения инфекции от матери к плоду является восходящий и гематогенный путь. Смешанный путь инфицирования фетоплацентарного комплекса в литературе недостаточно освещен. В эпоху так называемой «иммунодефицитной прослойки населения» патофизиологические механизмы формирования инфицирования плода остаются не изученными, поэтому исследования в этом направлении являются актуальными. В данном обзоре отражен современный взгляд на этапы патогенеза внутриутробного инфицирования плода. Приведены актуальные точки зрения об этиологии, механизме восходящего, гематогенного и смешанного путях внутриутробного инфицирования. Рассмотрены последствия влияния инфекции на здоровье плода. Intrauterine infectious pathology is one of the main causes of the pathological course of pregnancy and childbirth. Transplacental infection of the fetus is considered one of the most likely causes of congenital malformations, which creates medical and social problems. The clinical picture of intrauterine infection during pregnancy does not always have specific features, which makes it difficult to diagnose. Transmission of an infectious pathogen during pregnancy from mother to fetus largely depends on the functioning of a woman’s immune system. The main routes of infection from the mother to the fetus are the ascending and hematogenic pathways. The mixed pathway of infection of the fetoplacental complex is insufficiently covered in the literature. In the era of the so-called “immunodeficiency stratum of the population”, the pathophysiological mechanisms of fetal infection formation remain unexplored, therefore, research in this direction is relevant. This review reflects the current stages of the pathogenesis of intrauterine infection of the fetus. The current points of view on the etiology, mechanism of ascending, hematogenic and mixed pathways of intrauterine infection are presented. The effects of infection on fetal health are considered.

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.

Over the recent years, many advances have been made in the research of the genetic factors of pregnancy complications. In this work, we use publicly available data repositories, such as the National Human Genome Research Institute GWAS Catalog, HuGE Navigator, and the UK Biobank genetic and phenotypic dataset to gain insights into molecular pathways and individual genes behind a set of pregnancy-related traits, including the most studied ones—preeclampsia, gestational diabetes, preterm birth, and placental abruption. Using both HuGE and GWAS Catalog data, we confirm that immune system and, in particular, T-cell related pathways are one of the most important drivers of pregnancy-related traits. Pathway analysis of the data reveals that cell adhesion and matrisome-related genes are also commonly involved in pregnancy pathologies. We also find a large role of metabolic factors that affect not only gestational diabetes, but also the other traits. These shared metabolic genes include IGF2, PPARG, and NOS3. We further discover that the published genetic associations are poorly replicated in the independent UK Biobank cohort. Nevertheless, we find novel genome-wide associations with pregnancy-related traits for the FBLN7, STK32B, and ACTR3B genes, and replicate the effects of the KAZN and TLE1 genes, with the latter being the only gene identified across all data resources. Overall, our analysis highlights central molecular pathways for pregnancy-related traits, and suggests a need to use more accurate and sophisticated association analysis strategies to robustly identify genetic risk factors for pregnancy complications.

Objective. To compare the features of placental pathology in twin and singleton pregnancies complicated by early preeclampsia. Materials and methods. A retrospective analysis of 211 placental pathomorphological examinations in patients with early preeclampsia was performed. The first (study) group composed of placentas obtained from patients with twin pregnancy and early pre-eclampsia (n = 108); the second (comparison) group composed of placentas obtained from patients with singleton pregnancy and early pre-eclampsia (n = 103). Placental histopathological examination was conducted according to a generally accepted method with assessing the signs of circulatory disorders in the maternal-placental-fetal system and the degree of infectious and inflammatory lesions. Results. Fetal and placental massometric parameters were higher in the study group (p < 0.001); a subcompensated form of placental insufficiency, villous maturation disorders, intervillous hemorrhage and thrombosis, chorangiosis, and angiospastic arteriopathy (p < 0.001) were statistically significantly more common in the comparison group. Conclusion. Maternal and fetal vascular malperfusion was more pronounced in the group of singleton pregnancy with early preeclampsia, which indicates different pathophysiological mechanisms of early pre-eclampsia as opposed to multiple pregnancy. Key words: multiple pregnancy, placental pathomorphology, maternal and fetal vascular malperfusion, early pre-eclampsia

Aim. To evaluate the efficacy of cascade plasma filtration (CPF) for the correction of lipid profile and biochemical markers (sFlt-1, PIGF, sFlt-1/PIGF) in pregnant women with early preeclampsia. Materials and Methods. A prospective controlled study of 23 CPF procedures was conducted in 11 pregnant women with early preeclampsia at gestational ages 22 to 31 weeks. The evolution of clinical manifestations of preeclampsia (BP, urine output, and proteinuria), laboratory biochemical parameters (protein/creatinine ratio, lipid profile), blood coagulation tests, and thromboelastometry (ROTEM) were assessed. In addition, the effect of CPF on the level of preeclampsia markers (sFlt-1, PIGF, sFlt-1/PIGF-ratio) as predictors of endothelial aggression was analyzed. The efficacy of extracorporeal therapy was evaluated based on the duration of pregnancy prolongation. Results. The use of CPF as an adjunct for the treatment of early preeclampsia had a positive effect on the lipid profile by reducing cholesterol and LDL, which helped to decrease atherogenic aggression on the vascular endothelium. In addition, the extracorporeal therapy promoted reduction of the anti-angiogenic effect of sFlt-1, which was confirmed by a significant decrease in the sFlt-1/PIGF ratio from 515 [347; 750] to 378 [285; 557] (P = 0.013). The period of prolongation of pregnancy was longer in the main group (with CPF) and was 19 [5; 26] days, whereas in the comparison group (without CPF) it was 3 [1; 4] days (P < 0.001). All newborns were discharged from the hospital in a stable condition. The paper is supplemented with a clinical observation of the effective use of CPF in early preeclampsia. Conclusion. The use of cascade plasma filtration in the treatment of early preeclampsia to prolong pregnancy could be a promising approach.

A review of literature and our own experience in implementing the Patient Blood Management (PBM) approach in a level III maternity unit with a focus on postpartum hemorrhage was conducted. Based on a comparative analysis, the main directions of clinical and economic optimization of blood conservation techniques and correction of anemia in obstetrics were described. The results of introducing into daily practice rotational tests (ROTEM) as a routine method of assessing the blood coagulation system were presented. A comparative sensitivity analysis of the results of thromboelastometry and hemostasis screening test in pathological obstetric hemorrhage was conducted. On the basis of the analysis performed, the advantages of implementing the key strategies of PBM in the maternity unit in terms of clinical and economic efficiency and transfusiology safety were demonstrated. Key words: patient blood management, ROTEM test, placenta accreta, blood salvage (Cell Saver), autologous blood donation