Obstetric Syndrome Research Articles

Перебіг вагітності та пологів у жінок із прееклампсією

Purpose - to determine the features of pregnancy and childbirth in women who had complications from the group of major obstetric syndromes (MOS), which were clinically manifested by pre-eclampsia. Materials and methods. A retrospective clinical and statistical analysis of the course of pregnancy and childbirth in 103 pregnant women with pre-eclampsia (main group - MG) was performed. The control group (CG) included 56 practically healthy pregnant women with a favorable reproductive history and uncomplicated pregnancy. Statistical processing of the study results was performed using standard software Microsoft Excel 5.0 and Statistica 6.0. Results. Moderate pre-eclampsia prevailed in pregnant women of MG - 71 (69.6%) cases versus 2 (3.5%) cases in CG (p<0.05). Severe pre-eclampsia was observed in almost every third pregnant woman of MG - 31 (30.4%) cases. One of the main complications of the third trimester of gestation, as well as in the first and second trimesters, was gestational anemia - 38 (37.2%) cases in MG versus 14 (25.0%) cases in CG (p<0.05). Placental insufficiency was significantly more common in pregnant women of MG - 33 (32.1%) cases versus 2 (3.5%) cases in CG (p<0.05); which led to the development of fetal growth retardation syndrome in 10 (9.7%) cases in MG. The threat of preterm birth was noted in 16 (15.6%) cases in MG versus 4 (7.1%) cases in CG (p<0.05), preterm birth was noted - in 12 (11.7%) cases, and the incidence of cesarean section was 32 (31.1%) cases versus 5 (8.9%) cases (p<0.05). Conclusions. The features of the course of pregnancy and childbirth in women with MOS, which is clinically manifested by the development of pre-eclampsia, are characterized by a significantly high frequency of threatened abortion, gestational anemia, bacterial vaginosis, placental insufficiency, fetal growth retardation syndrome, premature rupture of membranes, premature birth, premature detachment of a normally located placenta, fetal distress and, as a result of these complications, an increase in the incidence of caesarean section to 31.1%. The study was conducted in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the Local Ethics Committee of the institution mentioned in the paper. Informed consent of women was obtained for the study. No conflict of interest was declared by the author.

Proteomic profile of extracellular vesicles in maternal plasma of women with fetal death

Objectives Fetal death is a complication of pregnancy caused by multiple etiologies rather than being the end-result of a single disease process. Many soluble analytes in the maternal circulation, such as hormones and cytokines, have been implicated in its pathophysiology. However, changes in the protein content of extracellular vesicles (EVs), which could provide additional insight into the disease pathways of this obstetrical syndrome, have not been examined. This study aimed to characterize the proteomic profile of EVs in the plasma of pregnant women who experienced fetal death and to evaluate whether such a profile reflected the pathophysiological mechanisms of this obstetrical complication. Moreover, the proteomic results were compared to and integrated with those obtained from the soluble fraction of maternal plasma. Methods This retrospective case-control study included 47 women who experienced fetal death and 94 matched, healthy, pregnant controls. Proteomic analysis of 82 proteins in the EVs and the soluble fractions of maternal plasma samples was conducted by using a bead-based, multiplexed immunoassay platform. Quantile regression analysis and random forest models were implemented to assess differences in the concentration of proteins in the EV and soluble fractions and to evaluate their combined discriminatory power between clinical groups. Hierarchical cluster analysis was applied to identify subgroups of fetal death cases with similar proteomic profiles. A p-value of <.05 was used to infer significance, unless multiple testing was involved, with the false discovery rate controlled at the 10% level (q < 0.1). All statistical analyses were performed by using the R statistical language and environment-and specialized packages. Results Nineteen proteins (placental growth factor, macrophage migration inhibitory factor, endoglin, regulated upon activation normal T cell expressed and presumably secreted (RANTES), interleukin (IL)-6, macrophage inflammatory protein 1-alpha, urokinase plasminogen activator surface receptor, tissue factor pathway inhibitor, IL-8, E-Selectin, vascular endothelial growth factor receptor 2, pentraxin 3, IL-16, galectin-1, monocyte chemotactic protein 1, disintegrin and metalloproteinase domain-containing protein 12, insulin-like growth factor-binding protein 1, matrix metalloproteinase-1(MMP1), and CD163) were found to have different plasma concentrations (of an EV or a soluble fraction) in women with fetal death compared to controls. There was a similar pattern of change for the dysregulated proteins in the EV and soluble fractions and a positive correlation between the log2-fold changes of proteins significant in either the EV or the soluble fraction (ρ = 0.89, p < .001). The combination of EV and soluble fraction proteins resulted in a good discriminatory model (area under the ROC curve, 82%; sensitivity, 57.5% at a 10% false-positive rate). Unsupervised clustering based on the proteins differentially expressed in either the EV or the soluble fraction of patients with fetal death relative to controls revealed three major clusters of patients. Conclusion Pregnant women with fetal death have different concentrations of 19 proteins in the EV and soluble fractions compared to controls, and the direction of changes in concentration was similar between fractions. The combination of EV and soluble protein concentrations revealed three different clusters of fetal death cases with distinct clinical and placental histopathological characteristics.

Assessing maternal cardiac function by obstetricians: technique and reference ranges

A strong body of evidence has now coalesced indicating that some obstetrical syndromes may result from maladaptive responses of the maternal cardiovascular system. Longitudinal studies have shown that these changes are complex and present before the clinical recognition of preeclampsia and fetal growth restriction, suggesting that hemodynamic maladaptation may play an etiologic role in obstetrical complications. Chronic hypertension is one of the most frequent complications of pregnancy, and recent evidence suggests that control of mild hypertension in early pregnancy improves outcome. The management of chronic hypertension can be improved by understanding specific cardiovascular hemodynamic abnormalities such as increased cardiac output or increased systemic vascular resistance, which can respond to either beta or calcium channel blockers, depending on the hemodynamic findings. Evaluation of maternal cardiac function has not been previously available to obstetrical healthcare providers using diagnostic ultrasound equipment used for fetal evaluation. Obstetrical ultrasound machines may be configured for various probes (endovaginal, abdominal, 3D/4D, and cardiac). This study used a cardiac probe placed in the suprasternal notch to image and measure the descending aorta diameter and the velocity time integral using pulsed and continuous wave Doppler ultrasound in normal pregnant women between 11 and 39 weeks of gestation. These measurements were followed by computation of maternal left ventricular preload, afterload, contractility, and blood flow. This was a prospective cross-sectional study. A total of 400 pregnant women were recruited between 11 and 39 weeks of gestation. Imaging of the maternal aortic arch was performed by placing a cardiac probe in the suprasternal notch to identify the aortic arch using 2D and color Doppler ultrasound. The end-systolic diameter of the aorta was measured at the junction of the left subclavian artery with the descending aorta, which was followed by insonation of the descending aorta to obtain the Doppler waveform. Following insonation of the descending aorta, measurements of the aortic diameter, velocity time integral, ejection time, mean pressure gradient, heart rate, maternal weight and height, and systolic and diastolic blood pressures were entered into an Excel spreadsheet to compute the following: (1) preload measurements of stroke volume, stroke volume index, and stroke work index; (2) afterload measurements of systemic vascular resistance and the potential-to-kinetic energy ratio; (3) contractility measurements of inotropy and the Smith-Madigan inotropy index; and (4) blood flow measurements of cardiac output and the cardiac output index. Fractional polynomial regression analysis was performed for each of the above measurements using gestational age as the independent variable. The diastolic and mean arterial blood pressure decreased from 11 to 18 weeks of gestation and then increased until term. The afterload measurements demonstrated similar characteristics, as all values decreased from 11 weeks until the mid and late second trimester, after which all values increased until term. Changes in contractility demonstrated an increase from 11 weeks to 25 to 28 weeks, followed by a decline until term. Changes in blood flow demonstrated an increase from 11 to 27 weeks and then declined until term. The continuous wave Doppler values were greater than the pulsed Doppler values except for the contractility measurements. Examples of abnormal cardiac measurements were identified in pregnant patients with hypertension and fetal growth restriction. An Excel calculator was created to provide quick computation of z-score measurements and their corresponding centiles described in this study. The technique for evaluation of maternal cardiac function described in this study would allow screening of maternal left ventricular preload, afterload, contractility, and blood flow in the obstetrical clinical milieu once a cardiac probe is acquired for obstetrical ultrasound machines used for fetal evaluation. The above measurements would allow the clinician to select appropriate hypertensive medication on the basis of the results of the evaluation of the maternal left ventricle.

Риски венозных тромбоэмболических событий при больших акушерских синдромах

Aim: Based on the study of the history, course of pregnancy and childbirth, to assess the risks of venous thromboembolic events among women with major obstetric syndromes. Design: Retrospective cohort study using the continuum sampling method. Materials and methods. 200 birth histories were analyzed: group 1 — 55 women with great obstetric syndromes, group 2 — 145 pregnant without them. The history of women, pregnancy outcomes were studied, and an analysis of the risks of venous thromboembolic complications was carried out. Results. Anamnestic risk factors for major obstetric syndromes were a family history aggravated by early thromboembolic events (RR = 3,13; 95% CI: 1,34–7,30), unemployed status (RR = 1,73; 95% CI: 1,32–2,65), preeclampsia in the past (RR = 23,46; 95% CI: 1,28–428,80), first pregnancy (RR = 1,63; 95% CI: 1,04–2,55), chronic arterial hypertension (RR = 8,45; 95% CI: 1,76–40,66). There was a significant increase in the risk of venous thromboembolic complications in patients of group 1 during pregnancy (1 (1–2) points; p &lt; 0.001) and in the postpartum period (3 (1–4) points; p &lt; 0.001). Conclusion. Prognostic markers of great obstetric syndromes were aggravated family and personal obstetric anamnesis, parity, low social status, chronic arterial hypertension. A significant increase in the risk of venous thromboembolic complications in pregnant women and puerperas with major obstetric syndromes was revealed. Keywords: great obstetric syndromes, preeclampsia, risk factors, venous thromboembolic complications.

ОЦЕНКА БЛИЖАЙШИХ И ОТДАЛЕННЫХ РЕЗУЛЬТАТОВ АКУШЕРСКОГО КРОВОТЕЧЕНИЯ С ЭМБОЛИЗАЦИЕЙ МАТОЧНЫХ АРТЕРИЙ И ПЕРЕНЕСЕННОЙ КОРОНАВИРУСНОЙ ИНФЕКЦИЕЙ (КЛИНИЧЕСКИЙ СЛУЧАЙ)

The study aims to present a complicated clinical case of a woman who almost died due to comorbid obstetric pathology associated with a coronavirus infection. The term “near miss” refers to the detailed analysis of each clinical case classified as a critical obstetric condition, as well as the registration of patients with such conditions in the Russian register established in 2021 to prevent maternal mortality and make management decisions. A severe clinical near miss case of a female patient included the following serious obstetric syndromes: postpartum obstetric hemorrhage followed by uterine artery embolization, endomyometritis by the third day, partial thrombosis of the branches of the right lower lobe pulmonary artery by the seventh day, thrombosis of parametrial vessels, partial necrosis of the uterus by the eighth day, and a new coronavirus infection COVID-19 by the thirteenth day after delivery. The complexity of diagnosis and treatment is demonstrated in the results of the study in the acute period and in the outcome of the disease.

Accelerated epigenetic clock aging in peripheral blood is associated with obstetric metabolic syndrome-related outcomes

Epigenetic clocks use CpG DNA methylation (DNAm) to estimate biologic age; acceleration is associated with diabetes mellitus (DM), heart disease, and shorter life. It is unknown if DNAm age is also related to cardiometabolic outcomes in pregnancy. AgeAccelGrim is a novel epigenetic clock that combines 7 DNAm components. We sought to determine if AgeAccelGrim is associated with obstetric metabolic syndrome.

Функционирование системы гемостаза у новорожденных в норме и на фоне преэклампсии (обзор литературы)

Preeclampsia is one of the so-called major obstetrical syndromes and a cause of maternal and neonatal morbidity worldwide. In addition, preeclampsia increases the risk of maternal and neonatal cardiovascular disorders and cerebrovascular diseases in the future. During pregnancy, the pregnant mother undergoes significant changes in the functions of various organ systems to accommodate the developing fetus. The onset of preeclampsia can cause dysfunction of multiple organs and systems, including the homeostasis system. Its dysfunction is associated with the most serious thrombohemorrhagic complications (premature detachment of normally situated placenta, thrombosis, embolism, and bleeding). It is important to understand the relationship between the maternal and fetal homeostasis system functioning. The homeostasis system functioning in the fetus and newborn infant has specific characteristics expressed not only in the quantitative composition and the level of activity of its main links, but also in the qualitastive composition, as well as in the functioning mechanisms which differ from those in adults. The above specific characteristics help to achieve an important balance in the homeostasis system functioning. Preeclampsia, associated conditions and complications can disturb the existing balance and homeostasis system functioning in the fetus and newborn infant with the development of thrombohemorrhagic complications. KEYWORDS: homeostasis system, newborn infants, preeclampsia, specific characteristics of functioning, preterm newborn infants, pregnancy. FOR CITATION: Yupatov E.Yu., Kurmanbaev T.E., Mustafin I.G. et al. Hemostasis functioning in neonates: normal condition and condition in preeclampsia (literature review). Russian Journal of Woman and Child Health. 2023;6(2):199–205 (in Russ.). DOI: 10.32364/2618-8430- 2023-6-2-199-205.

Basic principles and structure of risk assessment of Great obstetrical syndromes

The objective: to develop a method for predicting the individual risk for great obstetric syndromes (GOS).Materials and methods. An analysis of the somatic, reproductive, and obstetric anamnesis was conducted in 572 pregnant women with clinical manifestations of GOS, in 81 of them (prediction group) signs of placental dysfunction were detected based on clinical, functional, laboratory, and ultrasound data. Control group (CG) – 50 practically healthy pregnant women with a favorable reproductive history and an uncomplicated course of this pregnancy.Functional, biophysical, hormonal, immunological and hemocoagulation indicators were calculated to determine the informative (prognostic) significance. Quantitative signs were divided into diagnostic intervals, and qualitative signs were assigned a code. The following indicators were included in the standard protocol: age, data on somatic and gynecological history, data on the pregnancy course, results of functional and laboratory examinations. Statistical processing of research results was carried out using standard Microsoft Excel 5.0 and Statistica 6.0 programs. Results. In the I trimester of pregnancy the concentration of placental lactogen (PL) in the prediction group was 29.4 % lower than the CG indicator, estradiol (E2) amount – by 27.4 %, estriol (E3) – by 28.6 %, progesterone (PG) – by 34.4%, human chorionic gonadotropin (hCG) – by 28.3 % lower, and cortisol (CR) – by 36.1 % higher. At the beginning of the II trimester of pregnancy in the prediction group the level of PL was already reduced by 33.8 %, E2 – by 26.2 %, E3 – by 32.3 %, PG – by 37.4 %, hCG – by 30.6 %, and CR – increased by 43.6 % compared to CG.The indicators of placenta hormonal activity in the early stages of pregnancy and at the beginning of the II trimester can be prognostic signs of further disruption of the adaptive compensatory and adaptive reactions of the fetal placental complex (FPC) in the II and III trimesters of pregnancy. Among a wide range of hemostasiological indicators in the I trimester of pregnancy in the prediction group the most informative were: activated partial thromboplastin time (-23 %) and activated recalcification time (+16.2 %), the changes of which remained at the beginning of the II trimester (-40% and - 11.7% respectively). During the evaluation of thromboelastogram data, the value of “r+k” was fixed by 33.3 % lower in the I trimester and by 36 % – at the beginning of the II trimester of pregnancy. As a result of the analysis the indicators with a high information value (more than 3.0 c.u.) were selected for quantitative assessment of the degree of individual risk for the development of maladaptive disorders in the FPC. The clinical trial of the scoring method of prediction proved its high sensitivity (91.8 %) and specificity (85.6 %). Conclusions. A multi-faceted analysis of anamnestic data, features of the pregnancy course, basic clinical, laboratory and functional indicators in women with clinical manifestations of GOS made possible to develop an effective methodology for predicting the risk for GOS development with high levels of sensitivity and specificity.

Incorporando la bioética ambiental a los cuidados materno perinatales para disminuir los riesgos de la Pan-Sindemia en el proceso reproductivo.

Until now, the bioethical approach to maternal perinatal care is projected from the integral vision of bio-psycho-social health, the perspective of Human Rights and the gender perspective. In general, the ecological bioethics that arises from the perspective of environmental health has not been incorporated into maternal-perinatal care with regard to “global ethics”, environmental bioethics, the perspective of “consilience” and the importance of the healthy environment as a human right. The current global crisis situation due to the combination of the COVID 19 Pandemic and the Global Syndemic, characterized as Pan Syndemic, increases the risks and damages in the reproductive process, especially in populations violated in their rights. JUSTIFICATION It is necessary to minimize the effect of the Pan Syndemic on the human reproductive process. On the global agenda, humanity must reverse the causes of the Pan Syndemic. Meanwhile, health professionals and teams must reformulate their role when it comes to maternal-perinatal care, incorporating into the clinic the right to a healthy environment for reproduction. PERSPECTIVES Modifications in the clinical practice of sexual and reproductive health teams should be aimed at: incorporate ecological bioethics into maternal perinatal care from training to clinical practice; develop a comprehensive approach to major perinatal obstetric syndromes, prematurity and fetal growth restriction, to minimize the impact of the Pan Syndemic on the human reproductive process.

Study of pathological changes in placentas of gestational diabetes mellitus and its association with fetal outcome

GDM is associated with an adverse fetal and neonatal outcome that often presents with macrosomia, birth trauma, neonatal hypoglycemia, and respiratory distress syndrome. The inclusion of GDM into 'the great obstetrical syndromes' emphasizes the role of the placenta in interactions between the maternal and fetal unit. &#x0D; The aim: To study pathological changes in the placentas of gestational diabetes mellitus and its association with fetal outcome.&#x0D; Materials and methods: The Prospective study was conducted among pregnant women above the age of 18 years diagnosed with gestational diabetes attending the hospital. All patients are subjected to complete physical examination along with obstetric examination. All the routine investigations, including the complete blood counts, blood picture, RBS, RFT, LFT, OGTT, CUE and, ultrasonography with doppler, histopathological examination of the placenta after delivery.&#x0D; Results: The weight of the babies born to GDM mothers and normal mothers were compared, and the GDM mother's baby weighed higher, meaning diabetes has an effect on the baby's weight which was statistically significant. Comparison of the placenta was made for cases and controls; the result suggested all the morphological parameters placenta - weight (p&lt;0.001), diameter (p&lt;0.001), area (p&lt;0.002) and thickness (p&lt;0.001) were statistically significant. The complications reported were respiratory complications, hypoglycemia, hyperbilirubinemia, meconium staining, polycythemia, sepsis and hypocalcemia. Babies of gestational diabetic mothers have a higher risk of developing neonatal complications than non-diabetic mothers. Villous oedema, villous fibrosis, syncytial knots, and fibrinoid necrosis is seen on histopathological examination was &lt;0.05, and hence there was a significant difference between these findings in both the groups.&#x0D; Conclusions: GDM is associated with the adverse fetal and neonatal outcome that often presents with respiratory complications, hypoglycemia, hyperbilirubinemia, meconium staining, polycythemia, sepsis and hypocalcemia. Including GDM into 'the great obstetrical syndromes' emphasizes the role of the placenta in interactions between the maternal and fetal unit

Peculiarities of clinical characteristics of pregnant with symptoms of Great obstetrical syndromes

The objective: to establish the risk factors for development of great obstetrical syndromes (GOS) on the basis of a prospective analysis of somatic, reproductive, obstetric anamnesis in pregnant women with clinical manifestations of GOSMaterials and methods. We conducted the analyses of somatic, reproductive and obstetrical history of 572 pregnant with clinical symptoms of GOS, who had the following complications: 21 – preeclampsia, 38 – preterm deliveries, 13 – placental abruption, 457 – gestational anemia, 27 – intrauterine growth retardation, 16 – fetal distress, that were diagnosed based on clinical, functional, laboratory, ultrasound, cardiotocographic and morphological investigations. All these complications are included in the group of GOS.Statistical analyze was conducted by using standard programs of Microsoft Excel 5.0 and Statistica 6.0.Results. The average age of the pregnant women was 26.5±2.3 years, most of them were in young reproductive age. The prevailing diseases in the structure of somatic pathology were thyroid gland pathology – 427 (74.6 %) persons, anemia 182 (31.8 %), arterial hypertension – 114 (19.9 %), kidney diseases – 241 (42.1 %) and diseases of gastro-intestinal tract –187 (32.7 %). Disorders of menstrual cycle were determined in 137 (23.9 %) women, chronic pelvic inflammatory diseases – 98 (17.1 %), background diseases of cervix (erosion, cervical dysplasia) had 142 (24.8 %) patients in anamnesis, colpitis – 296 (51.7 %), polycystic ovaries – 74 (12.9 %). The following pregnancy complications were diagnosed as preeclampsia – in 21 (3.7 %) persons, threatened preterm interruption of pregnancy in different gestational terms – in every third pregnant women (192 individuals – 33.7 %), anemia – 457 (79.9 %), preterm delivery – 38 (6.6 %) women, placental abruption – 13 (2.3 %), fetal growth retardation – in 27 cases (4.7 %), fetal distress – 16 (2.8 %). The rate of cesarean section in this group was 28.8 %.Conclusions. The identified peculiarities of somatic, reproductive history and obstetrical and perinatal pathology in pregnant with complications from GOS group allowed to define the following risk factors of their development: young reproductive age, significant frequency of socio-hygienic, medical and demographic and socio-psychological problems, complicated somatic, gynecological and reproductive history.

Профілактика і прогнозування розвитку плацента-асоційованих ускладнень у пацієнтки з обтяженим тромботичним та акушерським анамнезом (клінічний випадок)

Purpose - to analyze the effectiveness of the timely appointment of pathogenetically justified secondary prevention in a patient with a burdened thrombotic and obstetric anamnesis based on the assessment of the course of pregnancy and the postpartum period in this woman. Clinical case. A woman with fetal loss syndrome and recurrent venous thrombosis applied for a consultation to plan pregnancy. The examination revealed a homozygous polymorphism of the F2-prothrombin gene (-20210 G&gt;A), a decrease in protein S activity to the level of 35%, which indicated an extremely high risk of thromboembolic complications. Pregnancy occurred on the background of anticoagulant therapy in combination with pregravid cofactor vitamin therapy. During pregnancy, the patient received low molecular weight heparins in therapeutic doses in combination with acetylsalicylic acid at a dose of 150 mg per day, diosmin 600 mg and cofactor vitamin therapy. According to the results of combined screening in the I trimester, with the calculation of the risks of preeclampsia, the woman was classified as a high risk group for its development. At 23-24 and 32-33 weeks of gestation, an analysis was performed to calculate the risk of perinatal complications in the II-III trimesters by determining the ratio of water-soluble tyrosine kinase-1 / placental growth factor (Sflt-1/PlGF). The data obtained indicated that the preventive therapy prescribed to the patient was adequate and effective. The pregnancy was completed at the full 37 weeks of gestation by spontaneous delivery in cephalic presentation without complications. A boy was born weighing 2950 g, Apgar score - 7/8. Conclusions. The clinical case is a vivid example of how well-timed, adequate prophylactic therapy can work efficiently and effectively, even in women with a rather burdensome thrombotic and obstetric history. This case confirms the necessity and expediency of using the entire modern diagnostic arsenal that exists in Ukraine to predict the occurrence of «Great» obstetric syndromes, which to this day occupy one of the leading places in the structure of maternal and perinatal losses. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Differential affinity chromatography reveals a link between Porphyromonas gingivalis-induced changes in vascular smooth muscle cell differentiation and the type 9 secretion system.

Porphyromonas gingivalis is implicated in adverse pregnancy outcome. We previously demonstrated that intrauterine infection with various strains of P. gingivalis impairs the physiologic remodeling of the uterine spiral arteries (IRSA) during pregnancy, which underlies the major obstetrical syndromes. Women diagnosed with IRSA also have a greater risk for premature cardiovascular disease in later life. The dysregulated plasticity of vascular smooth muscle cells (VSMCs) is present in both IRSA and premature cardiovascular events. We hypothesized that VSMCs could serve as a bait to identify P. gingivalis proteins associated with dysregulated VSMC plasticity as seen in IRSA. We first confirmed that dams with P. gingivalis A7UF-induced IRSA also show perturbed aortic smooth muscle cell (AoSMC) plasticity along with the P. gingivalis colonization of the tissue. The in vitro infection of AoSMCs with IRSA-inducing strain A7UF also perturbed AoSMC plasticity that did not occur with infection by non-IRSA-inducing strain W83. Far-Western blotting with strain W83 and strain A7UF showed a differential binding pattern to the rat aorta and primary rat AoSMCs. The affinity chromatography/pull-down assay combined with mass spectrometry was used to identify P. gingivalis/AoSMC protein interactions specific to IRSA. Membrane proteins with a high binding affinity to AoSMCs were identified in the A7UF pull-down but not in the W83 pull-down, most of which were the outer membrane components of the Type 9 secretion system (T9SS) and T9SS cargo proteins. Additional T9SS cargo proteins were detected in greater abundance in the A7UF pull-down eluate compared to W83. None of the proteins enriched in the W83 eluate were T9SS components nor T9SS cargo proteins despite their presence in the prey preparations used in the pull-down assay. In summary, differential affinity chromatography established that the components of IRSA-inducing P. gingivalis T9SS as well as its cargo directly interact with AoSMCs, which may play a role in the infection-induced dysregulation of VSMC plasticity. The possibility that the T9SS is involved in the microbial manipulation of host cell events important for cell differentiation and tissue remodeling would constitute a new virulence function for this system.

Peroxiredoxin2 regulates trophoblast proliferation and migration through SPIB-HDAC2 pathway

Adequate proliferation and migration of placental trophoblasts is the prerequisite of a successful pregnancy. Peroxiredoxin2 (Prdx2) is a multi-functional gene involved in various signal events to maintain essential biological functions and normal cellular homeostasis. In this study, substantially lower Prdx2 levels were found in the first trimester cytotrophoblasts of women who suffered from recurrent miscarriage (RM). Prdx2 downregulation inhibited trophoblast proliferation and migration. We demonstrated that histone deacetylase2 (HDAC2) acts downstream of Prdx2 in regulating trophoblast proliferation and migration. HDAC2 deacetylates histone-3-lysine-9 in E-cadherin (E-cad) promoter and reduces the transcription of E-cad epigenetically, whereas it promotes the expression of Slug and Snail genes. These molecular changes may contribute to the trophoblast epithelial-mesenchymal transition. We further verified whether Prdx2 modulated the expression of HDAC2 through SPIB. SPIB could bind to the HDAC2 promoter PU-box region and induce HDAC2 expression. In RM, down-regulated Prdx2 suppresses SPIB-HDAC2 pathway, leading to increased E-cad and decreased Slug and Snail, and eventually restrains trophoblast proliferation and migration. Our study unveils the role of Prdx2-regulated SPIB-HDAC2 pathway in the pathology of RM and provides diagnostic and therapeutic targets for RM as well as other “great obstetrical syndromes” including preeclampsia and intrauterine growth restriction.

Nutrition versus Great Obstetric Syndrome: A Bridge too Far?

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Single-Cell Immunobiology of the Maternal-Fetal Interface.

Pregnancy success requires constant dialogue between the mother and developing conceptus. Such crosstalk is facilitated through complex interactions between maternal and fetal cells at distinct tissue sites, collectively termed the "maternal-fetal interface." The emergence of single-cell technologies has enabled a deeper understanding of the unique processes taking place at the maternal-fetal interface as well as the discovery of novel pathways and immune and nonimmune cell types. Single-cell approaches have also been applied to decipher the cellular dynamics throughout pregnancy, in parturition, and in obstetrical syndromes such as recurrent spontaneous abortion, preeclampsia, and preterm labor. Furthermore, single-cell technologies have been used during the recent COVID-19 pandemic to evaluate placental viral cell entry and the impact of SARS-CoV-2 infection on maternal and fetal immunity. In this brief review, we summarize the current knowledge of cellular immunobiology in pregnancy and its complications that has been generated through single-cell investigations of the maternal-fetal interface.

Identification of vascular endothelial growth factor in preeclampsia in Iraqi women.

Preeclampsia (PE) is a major obstetric syndrome and represents a pregnancy hypertensive disease affecting about 2-8% of pregnancies. Typically, it occurs after 20 weeks of pregnancy, being classified as early or late in accordance with the gestational age at diagnosis or delivery. An imbalance between angiogenic and antiangiogenic factors has an important role in the pathophysiology of PE. It was hypothesized that the dysfunctional endothelium contributes to the pathogenesis of PE. A change in the production of Vascular endothelial growth factor (VEGR), a biomarker of endothelial dysfunction, is associated with this disease, whether presenting an increase, decrease, or being at a normal level. This study examined the associations between VEGF and preeclampsia and the importance of this VEGF as a predictor of its severity. This case-control study included 50 patients with preeclampsia and 50 normotensive pregnant women in the control group. Venous blood was aspirated from each patient, and VEGF levels were measured from sera. The mean VEGF for patients with mild PE was 29.410±18.976 pg/ml, for those with severe PE it was 36.188±36.98 pg/ml, and for normotensive women it was 92.104±154.715 pg/ml. There were significant differences in VEGF levels between the studied groups (P=0.024). This study showed that serum VEGF levels were significantly reduced in patients with preeclampsia compared with normotensive pregnant women, suggesting marked endothelial dysfunction. This led to widespread vasoconstriction and, in turn, caused hypertension and proteinuria.

Maternal folate status and placental vascular malperfusion: Findings from a high-risk US minority birth cohort

IntroductionMaternal folate deficiency was associated with preeclampsia (PE) and PE was associated with placental maternal vascular malperfusion (MVM). However, no study has examined the association of maternal folate status with placental MVM. MethodsWe examined the association of maternal folate status and placental MVM in the Boston Birth Cohort. Primary exposure variables were maternal self-reported multivitamin supplement (<2, 3–5, >5 times/week) per trimester; and plasma folate levels (nmol/L) after birth. Primary outcome was presence/absence of placental MVM defined by the Amsterdam Placental Workshop Group standard classification. Covariates included demographics, chronic hypertension, clinically diagnosed PE, eclampsia and HELLP syndrome, gestational and pre-gestational diabetes, overweight/obesity, maternal cigarette smoking and alcohol use. Associations between folate and placental MVM were evaluated using multivariate logistic regressions. ResultsOf 3001 mothers in this study, 18.8% of mothers had PE, 37.5% had MVM. Mothers with the lowest self-reported frequency of folate intake had the highest risk of MVM (OR 1.45, 95% CI 1.03–2.05), after adjusting for the covariates. Consistently, among a subset of 939 mothers with plasma folate levels, folate insufficiency was associated with increased risk of MVM (OR 1.65, 95% CI 1.03–2.63), after adjusting for the covariables. As expected, mothers with low folate and placental MVM had highest rates of PE compared to those of high folate and no MVM (p < 0.001). DiscussionIn this high-risk birth cohort, low maternal folate status was associated with increased risk of placental MVM. Further investigation should explore the association between folate status, placental findings and the great obstetrical syndrome.

A hypothetical model of skewed DNA methylation balance in the enhancer regions containing differentially methylated cytosines associated with non-malignant complex diseases

Epigenome-wide association studies have been widely conducted over the past decade to identify the epigenetic determinants of human complex diseases. Numerous differentially methylated cytosines (DMCs) associated with diseases or environmental exposure have been identified till date. An important hallmark of DMCs in non-malignant complex diseases is that they are strongly enriched in CpG sites showing small changes to intermediate levels of methylation. This paradigm of subtle change in DMC methylation hampers our understanding of epigenetic regulation in non-malignant complex diseases and the application of DMCs as biomarkers in clinical practice. Herein, we propose a hypothetical model of skewed DNA methylation balance in the enhancer regions containing differentially methylated cytosines associated with non-malignant complex diseases. The DMCs are strongly enriched in enhancers, which are characterized by a highly dynamic balance of DNA methylation. The DNA methylation balance plays an important role in cellular adaptation to adverse environment; however, in the case of certain diseases, the balance becomes skewed toward one end of dynamic range. Binding stress-inducible transcription factors determines DNA methylation at the enhancer region, resulting in epigenetic heterogeneity. The dynamics of DNA methylation balance can be evaluated by analyzing the DNA co-methylation status of DMCs and their neighboring CpG sites. Targeted bisulfite resequencing method is suggested to analyze the change in DNA co-methylation in both case-control and longitudinal cohort studies. Cell models are necessary to study the molecular mechanisms of DNA methylation changes. We also suggest that complex obstetrical syndromes associated with placental disorders may be excellent models for investigating common features of DNA methylation in non-malignant complex diseases.

Pregnancy in women with Hereditary Angioedema due to C1-inhibitor deficiency: Results from the ITACA cohort study on outcome of mothers and children with in utero exposure to plasma-derived C1-inhibitor.

BackgroundIn women with Hereditary Angioedema (HAE) due to C1-inhibitor (C1INH) deficiency (C1INH-HAE), pregnancy counseling and treatment can be challenging. Despite the evidence of the immediate favorable outcome and safety of plasma-derived (pd)C1INH concentrate, there are no data regarding any difference among women who underwent or not pdC1INH during pregnancy or on children with in utero exposure to pdC1INH. The present interview study aimed at analyzing outcome of C1INH-HAE mothers and children according to pdC1INH-exposure during pregnancies.MethodsC1INH-HAE women who experienced at least 1 pregnancy were included from seven centers of the Italian Network for Hereditary and Acquired Angioedema (ITACA). The interview study retrospectively analyzed pregnancies who underwent (group 1) or not (group 2) pdC1INH. The overall goals of the study included immediate and long-term outcomes, in terms of outcomes in the time interval between pregnancy and survey.ResultsA total of 168 pregnancies from 87 included women were analyzed. At term delivery (>37 gestation-week, GW) has been registered in 73.8% of cases, while spontaneous abortion (SA) occurred in 14.2% of cases with a mean GW 7 ± 2. The group 1 including pdC1INH-treated pregnancies comprised a third of the cohort (51/168, time interval 1.5 ± 10.4 yrs), while the group 2 represented 69.6% (117/168, time interval 32.8 ± 14 yrs). The same prevalence of SA occurred when comparing group 1 (11.7%) with group 2 (15.4%) with a similar GW at SA. The group 1 was older at the pregnancy time and younger at the interview than the group 2 (P < 0.01 for both); moreover, the group 1 showed a higher prevalence of cesarean delivery (P < 0.0001). The overall prevalence of obstetrical syndromes was similar between two groups: however, gestational diabetes was described only in pdC1INH-untreated pregnancies. In utero pdC1INH-exposed children (n = 45) did not show differences compared with unexposed ones (n = 99) in neonatal short-term outcomes.ConclusionThrough appropriate management and counseling, most of C1INH-HAE women undergo successful pregnancy and delivery. For pregnant C1INH-HAE women being treated with pdC1INH, our findings are reassuring and might lead to an improvement of both the knowledge about treatments and the experience of HAE itself.