Obstetric Syndrome Research Articles

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.

Highlights from the International Twins Congress 2021

Highlights from the International Twins Congress 2021

Toward a new taxonomy of obstetrical disease: improved performance of maternal blood biomarkers for the great obstetrical syndromes when classified according to placental pathology

The major challenge for obstetrics is the prediction and prevention of the great obstetrical syndromes. We propose that defining obstetrical diseases by the combination of clinical presentation and disease mechanisms as inferred by placental pathology will aid in the discovery of biomarkers and add specificity to those already known. To describe the longitudinal profile of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and the PlGF/sFlt-1 ratio throughout gestation, and to determine whether the association between abnormal biomarker profiles and obstetrical syndromes is strengthened by information derived from placental examination, eg, the presence or absence of placental lesions of maternal vascular malperfusion. This retrospective case cohort study was based on a parent cohort of 4006 pregnant women enrolled prospectively. The case cohort of 1499 pregnant women included 1000 randomly selected patients from the parent cohort and all additional patients with obstetrical syndromes from the parent cohort. Pregnant women were classified into six groups: 1) term delivery without pregnancy complications (n=540; control); 2) preterm labor and delivery (n=203); 3) preterm premature rupture of the membranes (n=112); 4) preeclampsia (n=230); 5) small-for-gestational-age neonate (n=334); and 6) other pregnancy complications (n=182). Maternal plasma concentrations of PlGF and sFlt-1 were determined by enzyme-linked immunosorbent assays in 7560 longitudinal samples. Placental pathologists, masked to clinical outcomes, diagnosed the presence or absence of placental lesions of maternal vascular malperfusion. Comparisons between mean biomarker concentrations in cases and controls were performed by utilizing longitudinal generalized additive models. Comparisons were made between controls and each obstetrical syndrome with and without subclassifying cases according to the presence or absence of placental lesions of maternal vascular malperfusion. 1) When obstetrical syndromes are classified based on the presence or absence of placental lesions of maternal vascular malperfusion, significant differences in the mean plasma concentrations of PlGF, sFlt-1, and the PlGF/sFlt-1 ratio between cases and controls emerge earlier in gestation; 2) the strength of association between an abnormal PlGF/sFlt-1 ratio and the occurrence of obstetrical syndromes increases when placental lesions of maternal vascular malperfusion are present (adjusted odds ratio [aOR], 13.6 vs 6.7 for preeclampsia; aOR, 8.1 vs 4.4 for small-for-gestational-age neonates; aOR, 5.5 vs 2.1 for preterm premature rupture of the membranes; and aOR, 3.3 vs 2.1 for preterm labor (all P<0.05); and 3) the PlGF/sFlt-1 ratio at 28 to 32 weeks of gestation is abnormal in patients who subsequently delivered due to preterm labor with intact membranes and in those with preterm premature rupture of the membranes if both groups have placental lesions of maternal vascular malperfusion. Such association is not significant in patients with these obstetrical syndromes who do not have placental lesions. Classification of obstetrical syndromes according to the presence or absence of placental lesions of maternal vascular malperfusion allows biomarkers to be informative earlier in gestation and enhances the strength of association between biomarkers and clinical outcomes. We propose that a new taxonomy of obstetrical disorders informed by placental pathology will facilitate the discovery and implementation of biomarkers as well as the prediction and prevention of such disorders.

Porphyromonas gingivalis-mediated disruption in spiral artery remodeling is associated with altered uterine NK cell populations and dysregulated IL-18 and Htra1

Impaired spiral artery remodeling (IRSA) underpins the great obstetrical syndromes. We previously demonstrated that intrauterine infection with the periodontal pathogen, Porphyromonas gingivalis, induces IRSA in rats. Since our previous studies only examined the end stage of arterial remodeling, the aim of this study was to identify the impact of P. gingivalis infection on the earlier stages of remodeling. Gestation day (GD) 11 specimens, a transition point between trophoblast-independent remodeling and the start of extravillous trophoblast invasion, were compared to late stage GD18 tissues. P. gingivalis was found in decidual stroma of GD11 specimens that already had reduced spiral artery remodeling defined as smaller arterial lumen size, increased retention of vascular smooth muscle, and decreased invasion by extravillous trophoblasts. At GD11, P. gingivalis-induced IRSA coincided with altered uterine natural killer (uNK) cell populations, decreased placental bed expression of interleukin-18 (IL-18) with increased production of temperature requirement A1 (Htra1), a marker of oxidative stress. By GD18, placental bed IL-18 and Htra1 levels, and uNK cell numbers were equivalent in control and infected groups. However, infected GD18 placental bed specimens had decreased TNF + T cells. These results suggest disturbances in placental bed decidual stroma and uNK cells are involved in P. gingivalis-mediated IRSA.

The favorable outcome of subsequent pregnancy in a patient with a history of obstetric atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) is a severe life-threatening disease associated with uncontrolled activation of alternative complement pathway. Obstetric aHUS, which develops in pregnant women and puerperas, is characterized by a particularly severe course with multiple organ failure, high death risk and end-stage renal disease. The prognosis of patients with obstetric aHUS has changed dramatically after the introduction of eculizumab, a monoclonal antibody to C5 complement component, into clinical practice. With timely initiation of the complement blocking therapy, the patients would not only survive, but also completely restore the function of the affected organs. Naturally, the question arises on the possibility of repeated pregnancies in women with previous obstetric aHUS and on the strategy of pregnancy management.&#x0D; The paper describes a clinical case of successful treatment with eculizumab for obstetric aHUS in the third trimester of the first pregnancy in a young and previously healthy woman, and the management of her second pregnancy. A 23-year old woman at 35-36 weeks of her first pregnancy developed the clinical picture of obstetric thrombotic microangiopathy, which was interpreted as a manifestation of severe preeclampsia and HELLP syndrome. However, after an emergency surgical delivery, the patient's condition continued to deteriorate despite the plasma exchange procedure. After exclusion of the other causes of thrombotic microangiopathy, aHUS was diagnosed and treatment with eculizumab was started, which resulted in complete recovery. No aHUS-associated mutations were identified. The complement inhibitor treatment was discontinued after 12 months. Four years after the first birth, the patient had a second pregnancy after preconception planning. During pregnancy, the patient was closely monitored for a timely identification of potential complications and had prevention of placental complications with acetylsalicylic acid and low molecular weight heparin. No aHUS recurrence and/or other complications were observed, and the patient did not require treatment with eculizumab during pregnancy. Elective caesarean section was performed at 39 week of gestation. A healthy boy was born with a bodyweight of 3370 g, a height of 50 cm, and Apgar score 8-9.&#x0D; In women with obstetric aHUS history, a favorable outcome of repeated pregnancies is possible, in some cases even without any prophylactic use of complement-blocking therapy, provided that with complete remission of aHUS has been achieved, with close monitoring during gestation and prevention of placenta-associated complications.

Obstetric shock and shock in obstetrics - steady obstetrical syndrome.

Obstetric shock (OS) has been defined as a life-threatening cardiovascular collapse syndrome associated with pregnancy, childbirth and puerperium (obstetrics causes), and is the most significant cause of high maternal mortality (MM) throughout human history. Shock in obstetrics (SIO) refers to indirect causes of non-obstetrics causes in pregnancy, childbirth and puerperium (polytrauma, aesthetic incidents, cardiovascular or cerebrovascular incidents, other septic syndromes). The goals of OS treatment are: to quickly detect the location or cause of bleeding / injury / inflammation, prevent the progression of shock, prevent massive transfusions, preserve the uterus (and adnexa), and preserve fertility if possible. Surgical treatment of septic shock includes exploratory laparotomy (laparoscopy), ectomy or resection of the necrotized organ, abdominal lavage with multiple drainages, continuous peritoneal drainage with lavation, extensive triple antibiosis per admission or per antibiogram and thromboprophylaxis. OS seems to remain a permanent miasma in practical clinical obstetrics, which we will not be able to influence, because we have obviously caused today's increase in MM from haemorrhagic OS by iatrogenic increase in the number of caesarean sections, especially elective ones.

Комбінований пренатальний скринінг І триместру вагітності як прогностичний маркер розвитку «великих акушерських синдромів»

Purpose - to conduct an analysis of the combined prenatal screening of the trimester I of pregnancy in women who had complications from the group of great obstetric syndromes. Materials and methods. A retrospective statistical analysis of the combined prenatal screening of the trimester I was carried out. Of the 239 pregnant women (Group I - main) who had complications from the group of great obstetric syndromes, according to the data of the pregnancy monitoring exchange cards, combined prenatal screening of the trimester I was carried out in 65.3% of pregnant women, which amounted to 156 pregnant women who were divided into three subgroups: Ia (n=74) pregnant women with severe preeclampsia, Ib (n=40) pregnant women with placental insufficiency, clinically verified fetal growth retardation; Ic (n=42) of pregnant women with spontaneous premature birth in the gestation period of 22-36 weeks. The control group (CG) was 56 practically healthy pregnant women with a healthy reproductive history and an uncomplicated course of this pregnancy. Statistical processing of the research results was carried out using standard Microsoft Excel 5.0 and Statistica 6.0 programs. Results. In the Group I, the average term of trimester I screening was 12 weeks 3±4 days, in the CG - 12 weeks 1±3 days, the difference in the gestational term of the trimester I combined screening was statistically insignificant. The lowest level of PAPP-A was determined in subgroups Ia and subgroup Ic. In the Group I, the level of PAPP-A was on average 2.16 (1.35-3.24) IU/l and 0.836 (0.571-1.14) MoM, and in CG - 2.62 (1.82-4, 12) MO/l and 1.16 (0.786-1.7) MoM. According to the relative number of patients with a level of PAPP-A &lt;0.5 MoM, no significant differences were found between the Group I and CG, but in subgroup Ib the percent of such patients was the highest, which is significantly more than in CG. More significant differences were found at the level of PAPP-A &lt;0.3 MoM: in Group I there were 11 (7.05%) patients with a level of PAPP-A &lt;0.3 MoM, in CG - 1 (1.78%). The number of patients with a level of PAPP-A &gt;1.5 MoM, on the contrary, turned out to be the largest in CG - 15 (26.8%) compared to 23 (14.7%) in the Group I and with subgroup Ia - 9 (12.2%). The level of β-hCG in the studied groups was not statistically significant. There was no statistically significant difference in the thickness of the nuchal translucency, but in the Group I this indicator was slightly higher. The largest nuchal translucency value was in subgroup 1b. There were no statistically significant differences in the frequency of the absence of imaging of the nasal bone during ultrasound screening. According to the frequency of detection of reverse blood flow in the ductus venosus, it was not possible to detect statistically significant differences. This sign occurred only in 3 (1.92%) patients of the Group 1 (1 patient in each subgroup) and in 1 (1.78%) patient of CG. Conclusions. In patients who later developed pregnancy complications belonging to the group of great obstetric syndromes, in the trimester I, a number of prenatal screening indicators differ from those in patients with a physiological course of pregnancy. When conducting a standard set of prenatal diagnostics, the most significant differences were found in the level of PAPP-A (MoM). The results obtained during the analysis of PAPP-A are promising from the point of view of using this parameter as an element of the prognostic model of great obstetric syndromes for the successful course of pregnancy and the birth of a child with a normal body weight. The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the institution mentioned in the work. Women’s informed consent was obtained for the study. No conflict of interests was declared by the author.

Obstetric and perinatal pathology in pregnant women who had complications from the group of the Great Obstetrical Syndromes

The objective: to analyze the obstetric and perinatal outcomes of childbirth in pregnant women who had complications from the group of the great obstetrical syndromes.Materials and methods. A retrospective statistical analysis of obstetric and perinatal outcomes of childbirth of 239 pregnant women (the Ist group – main one) who had complications from the group of the great obstetrical syndromes (GOS). They were divided into three subgroups: Ia subgroup included 103 pregnant women with severe preeclampsia (PE), Ib subgroup – 67 pregnant women with placental insufficiency, with clinical manifestation of fetal intrauterine growth retardation (IUGR), Ic subgroup – 69 pregnant women with spontaneous preterm birth in the gestational age 22-36 weeks. The control group (CG) included 56 practically healthy pregnant women with a normal reproductive history and uncomplicated course of this pregnancy.Statistical processing of the study results was performed using standard programs Microsoft Excel 5.0 and Statistica 6.0.Results. The incidence of gestational diabetes mellitus in patients of the I group (28 (11.7 %) women) was higher than in CG (2 (3.6 %) persons). Cervical insufficiency was diagnosed in every fifth patient of Ic subgroup (12 (17.3 %) patients; χ2=15.56, p&lt;0.01; OR=9.25; CI 95%: 2.55–33.54 relative to CG), gestational anemia – in 179 (74.8 %) pregnant women in the I group and 18 (32.1 %) women in CG (p&lt;0.01).A significantly high rate of mild congenital malformations was present in subgroup Ib (7 (10.4 %) of pregnant women; χ2=12.67, p&lt;0.01; OR=7.93; CI 95%: 2.14-29.26). 21 patients in the I group had with antenatal fetal death, 6 (5.8 %) – severe PE, 11 (16.4 %) – IUGR. Five cases of early neonatal mortality was diagnosed in the I group. The rate of perinatal mortality in the I group was high and amounted to 108.7 ‰.The operative delivery in the I group was performed in 127 (53.1 %) patients which is significantly more than in CG (χ2=42.93, p&lt;0.01; OR=4.93; CI 95%: 2.99– 8.13). In 24 (18.9 %) pregnant women in the I group the indication for operative delivery was acute distress, which is significantly more than in CG (2 (3.6 %) women; χ2=7.36, p&lt;0.01; OR=5.17; CI 95%: 1.2–22.28). The mean score on the Apgar scale in newborns in CG was significantly higher compared with the I group (p&lt;0.01).Conclusions. The course of pregnancy and childbirth in women who had complications from the group of the great obstetrical syndromes was accompanied by the development of gestational diabetes, gestational anemia and cervical insufficiency. Complications such as fetal distress, severe preeclampsia, fetal growth retardation with decompensated hemodynamic disorders of the uterine and placental blood circulation, led to a high frequency of cesarean section in these patients.

Assessment of the risk of spontaneous preterm birth in pregnant women with the Dr. Arabin cervical pessary

BACKGROUND: Preterm birth has a multifactorial etiology, including both maternal and fetal complications, amid the effect of functionally impaired variants of multiple genes. Preterm birth is therefore considered as the major obstetric syndrome. One of the anatomical components of this syndrome is a short cervix, and a cervical pessary is used as a prevention of preterm birth in these patients.&#x0D; AIM: The aim of this study was to identify risk factors for spontaneous preterm birth in pregnant women who received a cervical pessary.&#x0D; MATERIALS AND METHODS: This prospective, open, randomized cohort study included 189 women with a singleton pregnancy and a short cervix (25 according to the Salomon scale) and a threatened miscarriage / preterm birth in the second and third trimesters trimester, who received the Dr. Arabin cervical pessary. We analyzed 183 parameters and identified the main risk factors leading to spontaneous preterm birth based on pregnancy outcomes.&#x0D; RESULTS: Based on the pregnancy outcomes, all patients were categorized into two main groups: group I included 167 women with term birth and group II consisted of 19 pregnant women with spontaneous preterm birth. The main risk factors for spontaneous preterm birth in singleton pregnancies in descending order were: the Bishop score 7 points (p = 0.00032, OR 12.38, 95 % CI [3.5043.87]), the modified Steinberg score 8 points (p = 0.00056, OR 10.55, 95% CI [3.0936.03]), cervical length 15 mm by transvaginal cervicometry (p 0.001, OR 7.94, 95% CI [2.8322.26]), history of preterm birth (p = 0.00128, OR 6.91, 95% CI [2.3220.56]), chronic placental insufficiency (p = 0.00307, OR 5.06, 95 % CI [1.8214.01]), genital anomalies (p = 0.07452, OR 5.03, 95% CI [1.1522.06]), and history of surgical manipulations on the cervix (p = 0.07003, OR 2.90, 95% CI [1.058.00]). In multivariate analysis, the risk of spontaneous preterm birth was five times higher in pregnant women with the concomitant presence of three risk factors: cervical length 15 mm, the modified Steinberg score 8 points, and the Bishop score 7 points (83.33% of spontaneous preterm birth compared to 16.67% of term birth; p 0.05, OR 59.29, 95% CI [6.47543.29]).&#x0D; CONCLUSIONS: Among patients with a short cervix and the Dr. Arabin cervical pessary, we have identified groups at higher risk for spontaneous preterm birth.

Соматичний та репродуктивний анамнез вагітних, які мали ускладнення із групи великих акушерських синдромів

Purpose - to conduct retrospective clinical and statistical analyses of somatic, reproductive history of mowen, with complications from the group of great obstetrical syndromes (GOS). Materials and methods. We conducted retrospective clinical and statistical analyses of somatic and reproductive history of 239 pregnant women (Ist - main group), who had coplications from the group of GOS, who were subdivided into 3 groups: Ia group (n=103) pregnant with severe preeclampsia, Ib group (n=67) pregnant with placenta insufficiency, with clinical manifestation by intrauterine growth retardation syndrome (IUGR); Ic group (n=69) pregnant with preterm delivery with gestational term 22-34 weeks. Control group (CG) was formed by 56 practically healthy pregnant with favourable reproductive history and non complicated course of current pregnancy. Statistical analyses was conducted by using standart programs Microsoft Excel 5.0 and Statistica 6.0. Results. We stated, that in I group the incidence of complicated heredity of cardiovascular pathology was significantly higher: 69 (28.8%) in I group (χ2=5.46, р=0.03, OR=2.79, CI 95% 1.14-6.79), in CG this factor was diagnosed only in 4 (7.1%) of patients. In subgroup Ib (patients with IUGR of 2-3 stage) the incidence of abortions and miscarriages in history was higher: in subgroup Ib these parameters were 0.83 (1.37) and 0.32 (0.59) correponding, and in CG - 0.19 (0.85) and 0.07 (0.42) corresponding (р&lt;0.05). The most reasonable difference compated to CG were diagnosed in patients from Ic subgroup (patients with spontaneous preterm deliveries). The highest incidence of patiens with obesity was diagnosed in subgroups Ia and Ic - 18 (17.5%) and 16 (23.2%), the difference compared to CG clinically significant (р&lt;0.01). A high incidence of anemia was noted in pregnant, especially among the ones with pregnancy complications - in I group anemia was diagnosed in more that half of patients - in 179 (74.8%), in CG - every third - in 18 (32.1%) (χ2=21.48, р&lt;0.01, OR=2.95, CI 95% 1.85-4.71). The data in CG are approximately the same as the incidence of this pathology in population of pregnant women of Ukraine. Diseases, characterized by elevated blood pressure in group I were diagnosed several times higher, compared to CG - 41 (17.1%) compared to 5 (8.9%) (χ2=11.1, р&lt;0.01, OR=6.08, CI 95% 1.84-20.1). In subgroup Ia the incidence of patients with this pathology was the highest - 25.2% (n=26) (χ2=20.78, р&lt;0.01, OR=11.03, CI 95% 3.21-37.9). Results. Peculierities of somatic and reproductive history of pregnant were gisgnosed in pregnant, who had complications grom GOS group that may be high risk factors of significant increase of obstetrical and perinatal complications from materal and fetal side. The usage of routine treatment and prophylactic measures were not effective enough, that is quite convincing reason for making up a new approach for decreasing the incidence and severity of GOS in these patients, and their prophylaxis is a relevant problem of modern obstetrics. 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. No conflict of interests was declared by the author. Key words: retrospective analys, clinical and statistical analyses, somatic history, reproductive history, great obstetrical syndromes.

Clinical manifestations of Rift Valley fever in humans: Systematic review and meta-analysis.

Rift Valley fever (RVF) is an emerging, neglected, mosquito-borne viral zoonosis associated with significant morbidity, mortality and expanding geographical scope. The clinical signs and symptoms in humans are non-specific and case definitions vary. We reviewed and analysed the clinical manifestations of RVF in humans. In this systematic review and meta-analysis we searched on different dates, the Embase (from 1947 to 13th October 2019), Medline (1946 to 14th October 2019), Global Health (1910 to 15th October 2019), and Web of Science (1970 to 15th October 2019) databases. Studies published in English, reporting frequency of symptoms in humans, and laboratory confirmed RVF were included. Animal studies, studies among asymptomatic volunteers, and single case reports for which a proportion could not be estimated, were excluded. Quality assessment was done using a modified Hoy and Brooks et al tool, data was extracted, and pooled frequency estimates calculated using random effects meta-analysis. Of the 3765 articles retrieved, less than 1% (32 articles) were included in the systematic review and meta-analysis. Nine RVF clinical syndromes were reported including the general febrile, renal, gastrointestinal, hepatic, haemorrhagic, visual, neurological, cardio-pulmonary, and obstetric syndromes. The most common clinical manifestations included fever (81%; 95% Confidence Interval (CI) 69-91; [26 studies, 1286 patients]), renal failure (41%; 23-59; [4, 327]), nausea (38%; 12-67; [6, 325]), jaundice (26%; 16-36; [15, 393]), haemorrhagic disease (26%; 17-36; [16, 277]), partial blindness (24%; 7-45; [11, 225]), encephalitis (21%; 11-33; [4, 327]), cough (4%; 0-17; [4, 11]), and miscarriage (54%) respectively. Death occurred in 21% (95% CI 14-29; [16 studies, 328 patients]) of cases, most of whom were hospitalised. This study delineates the complex symptomatology of human RVF disease into syndromes. This approach is likely to improve case definitions and detection rates, impact outbreak control, increase public awareness about RVF, and subsequently inform 'one-health' policies. This study provides a pooled estimate of the proportion of RVF clinical manifestations alongside a narrative description of clinical syndromes. However, most studies reviewed were case series with small sample sizes and enrolled mostly in-patients and out-patients, and captured symptoms either sparsely or using broad category terms.

Current views on the assessment of vascular wall elasticity in pregnant women with arterial hypertension

Introduction. Arterial hypertension is the most common somatic pathology in pregnant women. Arterial hypertension is a factor of high risk for the development of severe preeclampsia, placental insufficiency, intrauterine growth restriction, premature birth, maternal and perinatal mortality, nervous disorder and vascular heart disease of newborns and women’s distant cardiovascular disorders. The pathogenesis of gestational complications is associated with pathology of placentation, endothelial dysfunction and a decrease in vascular elasticity. The pathogenesis has not studied yet. Nowadays there are no tests with enough sensitivity and specificity ensuring early diagnostics and risk identification at development of great obstetric syndromes. Aim of the study was to improve our understanding about a clinical and prognostic role of vascular wall elasticity in pregnant women with arterial hypertension. Materials and Methods. We searched publications and analyzed literature using various scientific databases, including Index Medicus, PubMed/MEDLINE, Embase, Cochrane Library and Russian scholarly journals related to obstetrics, gynecology, cardiology for the last 9 years. Results and Discussion. Today changes in the elastic properties of arteries is a modern marker of a high risk of cardiovascular events in patients with essentialhypertension. Endothelial dysfunction develops already in the early stages of arterial hypertension and initiates structural changes in the vascular wall and an increase in arterial stiffness. High activity of the sympathetic nervous system is the cause of changes in the elastic properties of arteries in pregnant women with arterial hypertension. Conclusion. The role of vascular wall elasticity in pregnant women with arterial hypertension is of tremendous importance and deserves close attention. The study of elastic properties of vessels is relevant for assessing the risk of gestational complications in pregnant women with arterial hypertension.

Co-expression analysis of placental genes in the search for key signaling pathways and biomarkers of the great obstetrical syndromes

Objective. To study the molecular mechanisms responsible for the development of diseases grouped within the great obstetrical syndromes (GOS) at the level of the transcriptome of human maternal placenta.Material and Methods. We gathered the results of genome-wide transcriptome studies of the human placental tissue using Gene Expression Omnibus (GEO) data repository for the following phenotypes: physiological pregnancy, preeclampsia (PE), premature birth, and intrauterine growth restriction (IUGR). Eleven data sets were selected and supplemented with our experimental data; a total of 481 samples of human placental tissue were included in the integrative analysis. Bioinformatic data processing and statistical analyses were performed in the R v3.6.1 software environment using the Bioconductor packages. The pooled dataset was used to search for common molecular targets for GOS via weighted gene co-expression network analysis (WGCNA). The functional annotation of genes and the resulting clusters was carried out with the DAVID database; protein-protein interaction network was built using the STRING software; and the hub genes for the network were identified using the MCC analysis with plugin cytoHubba in Cytoscape software 3.7.2.Results. We obtained a table of expression levels for 15,167 genes in 246 samples. Hierarchical clustering of this network allowed to find 55 modules of co-expressed genes in the group with PE, 109 modules in the group with PB, 75 modules in patients with IUGR, and 56 modules in the control group. The preservation analysis of co-expressed modules for the studied phenotypes suggested the presence of a common cluster comprising eight genes specific only for patients with PE and IUGR, as well as the module of 23 co-expressed genes typical only for patients with PB and IUGR. Protein-protein interaction network was built for these gene sets, and the SOD1, TXNRD1, and UBB genes were the central nodes in the network. Based on network topology evaluation with cytoHubba, six hub genes (rank ˂ 5) were identified as follows: SOD1, TKT, TXNRD1, GCLM, GOT1, and ACO1.Conclusion. The obtained results allowed to identify promising genetic markers for preeclampsia, intrauterine growth restriction, and miscarriage. Moreover, the study also made it possible to identify the most important overlapping molecular mechanisms of these diseases occurring in the placental tissue.

Почечная дисфункция и современные биомаркеры повреждения почек при HELLP-синдроме и акушерском атипичном гемолитико-уремическом синдроме

Почечная дисфункция и современные биомаркеры повреждения почек при HELLP-синдроме и акушерском атипичном гемолитико-уремическом синдроме

Gestation complications in women with metabolic syndrome: pathogenesis, diagnosis and prevention (literature review)

The article summarizes modern scientific views on the main links of pathogenesis, diagnostic criteria and methods for the prevention of gestational complications in women with metabolic syndrome. The aims of study is to analyze modern domestic and foreign studies on the study of pathogenetic mechanisms of influence of metabolic components syndrome for the development of gestational complications, methods of their diagnosis and prevention in women with metabolic syndrome. Results. It has been proven that the components of metabolic syndrome are associated with the development of pregnancy complications, such as pre-eclampsia, fetal growth retardation and macrosomia, gestational diabetes, preterm labour, fetal death, habitual early termination of pregnancy. On the basis of joint pathogenesis, the above-mentioned complications belong to the group of «the great obstetrical syndromes». It has been shown that pregnant women with metabolic syndrome are at high risk for the occurrence of «the great obstetrical syndromes» and require timely appointment of preventive measures to reduce them. Almost all scientific studies have demonstrated the importance of regulating metabolic processes in the body of a woman with metabolic syndrome at the stage of preconcepence period. It is reported that a lifestyle modification that aims to reduce body weight by prescribing a balanced low-calorie diet combined with exercise and the use of behavioral therapy leads to improved pregnancy outcomes for both mother and baby. The conclusion. The problem of metabolic syndrome in women of reproductive age remains relevant in modern medicine and taking into account its social significance, requires further research in the aspect of studying pathogenesis, early diagnosis and prevention of his pathology, since it can significantly improve the condition of the pregnant woman in the future and have a positive effect on the course of pregnancy and childbirth. No conflict of interest was declared by the authors. Keywords: metabolic syndrome, pregnancy, gestational complications, diagnosis, pathogenesis, prevention.

Acute Atherosis Lesions at the Fetal-Maternal Border: Current Knowledge and Implications for Maternal Cardiovascular Health.

Decidua basalis, the endometrium of pregnancy, is an important interface between maternal and fetal tissues, made up of both maternal and fetal cells. Acute atherosis is a uteroplacental spiral artery lesion. These patchy arterial wall lesions containing foam cells are predominantly found in the decidua basalis, at the tips of the maternal arteries, where they feed into the placental intervillous space. Acute atherosis is prevalent in preeclampsia and other obstetric syndromes such as fetal growth restriction. Causal factors and effects of acute atherosis remain uncertain. This is in part because decidua basalis is challenging to sample systematically and in large amounts following delivery. We summarize our decidua basalis vacuum suction method, which facilitates tissue-based studies of acute atherosis. We also describe our evidence-based research definition of acute atherosis. Here, we comprehensively review the existing literature on acute atherosis, its underlying mechanisms and possible short- and long-term effects. We propose that multiple pathways leading to decidual vascular inflammation may promote acute atherosis formation, with or without poor spiral artery remodeling and/or preeclampsia. These include maternal alloreactivity, ischemia-reperfusion injury, preexisting systemic inflammation, and microbial infection. The concept of acute atherosis as an inflammatory lesion is not novel. The lesions themselves have an inflammatory phenotype and resemble other arterial lesions of more extensively studied etiology. We discuss findings of concurrently dysregulated proteins involved in immune regulation and cardiovascular function in women with acute atherosis. We also propose a novel hypothesis linking cellular fetal microchimerism, which is prevalent in women with preeclampsia, with acute atherosis in pregnancy and future cardiovascular and neurovascular disease. Finally, women with a history of preeclampsia have an increased risk of premature cardiovascular disease. We review whether presence of acute atherosis may identify women at especially high risk for premature cardiovascular disease.

Artificial intelligence technologies in predicting preeclampsia

The strategy for preserving reproductive potential in the Russian Federation is focused on the personalized women’s health care and based on preclinical identification of gynecological diseases and major obstetric syndromes at the stage of predicting adverse outcomes and subsequent preventive measures able to reduce maternal and perinatal morbidity and mortality, decrease women and neonatal disability as well as profoundly reduce extremely high costs on care of premature infants. The search for effectivepredictive methods of preeclampsia (PE) at the stage of preconception and in the first trimester of pregnancy is driven by the desire to identify women at greater risk of developing hypertensive disorders in order to take the necessary effective measures forpreventing placental pathology as early as possible, thereby preventing or reducing incidence rate of PE. At the same time, identifying a group of high-risk women would allow to rationally plan prenatal care, timely recognize emergence of multiple organdysfunction and immediately begin pathogenetic and symptomatic therapy. Taking into account the national and global experience of using predictive analytics software proving their success in reproductive medicine, it is reasonable to assume that converting prognosis into digital format by using artificial intelligence (AI) algorithms will open new opportunities for increasing accuracy of individual risk calculation for PE by meeting current paradigm of personalized preventive medicine. Our scientific review on domestic and international publications aims to inform a wide range of obstetricians-gynecologists about advances in AI technologies as well as prospects for machine learning to predict PE.

Long-Term Consequences of Placental Vascular Pathology on the Maternal and Offspring Cardiovascular Systems.

Over the last thirty years, evidence has been accumulating that Hypertensive Disorders of Pregnancy (HDP) and, specifically, Preeclampsia (PE) produce not only long-term effects on the pregnant woman, but have also lasting consequences for the fetus. At the core of these consequences is the phenomenon known as defective deep placentation, being present in virtually every major obstetrical syndrome. The profound placental vascular lesions characteristic of this pathology can induce long-term adverse consequences for the pregnant woman’s entire arterial system. In addition, placental growth restriction and function can, in turn, cause a decreased blood supply to the fetus, with long-lasting effects. Women with a history of HDP have an increased risk of Cardiovascular Diseases (CVD) compared with women with normal pregnancies. Specifically, these subjects are at a future higher risk of: Hypertension; Coronary artery disease; Heart failure; Peripheral vascular disease; Cerebrovascular accidents (Stroke); CVD-related mortality. Vascular pathology in pregnancy and CVD may share a common etiology and may have common risk factors, which are unmasked by the “stress” of pregnancy. It is also possible that the future occurrence of a CVD may be the consequence of endothelial dysfunction generated by pregnancy-induced hypertension that persists after delivery. Although biochemical and biophysical markers of PE abound, information on markers for a comparative evaluation in the various groups is still lacking. Long-term consequences for the fetus are an integral part of the theory of a fetal origin of a number of adult diseases, known as the Barker hypothesis. Indeed, intrauterine malnutrition and fetal growth restriction represent significant risk factors for the development of chronic hypertension, diabetes, stroke and death from coronary artery disease in adults. Other factors will also influence the development later in life of hypertension, coronary and myocardial disease; they include parental genetic disposition, epigenetic modifications, endothelial dysfunction, concurrent intrauterine exposures, and the lifestyle of the affected individual.

Impact of interpregnancy interval on long-term childhood neoplasm of the offspring

Background The possible impact of interpregnancy interval (IPI) on perinatal outcomes has long been studied, however, a definition of the optimal interval is still not clear. Both short and long IPIs have been associated with obstetrical syndromes and short and long-term complications. In this study, we sought to explore the impact of IPI on the hazard for neoplasm of the offspring, thus contribute to the present literature in determining the preferred birth spacing. Objective We aim to investigate the association between short and long IPIs and the hazard for childhood neoplasm of the offspring. Methods A population-based retrospective cohort analysis comparing offspring neoplasm hazard following three different IPIs. Exposure was defined as short (<6 months), or long (>60 months) IPIs, whereas intermediate IPI (6 months − 60 months) served as the comparison group. The study included singleton live births in a tertiary regional hospital between 1991 and 2014. Offspring were followed for 18 years, and all hospitalization records for neoplasm diagnoses were collected. Kaplan–Meier survival curves were used for the cumulative incidence of neoplasm morbidity, and Cox proportional hazards models were used to control for confounders. Results During the study period, 144,397 deliveries met the inclusion criteria. Of those, 18,947 (13.1%) occurred in women with short IPI, 114,012 (79%) in women with intermediate IPI, and 11,438 (7.9%) in women with long IPI. 61 benign neoplasms and 80 malignant neoplasms were registered in offspring born after long IPI. The total percentage of neoplasm were the highest in the long IPI group versus the intermediate and short IPI groups (malignant − 0.7%, 0.6%, 0.5% respectively, benign − 0.5%, 0.4%, 0.3% respectively). Controlling for maternal age, diabetes mellitus, preterm delivery, birth weight, smoking, cesarean section, and fertility treatments, long IPI was found to be independently associated with high hazard for long-term pediatric neoplasm related hospitalizations (adjusted HR 1.39, 95% CI 1.09, 1.77). Short IPI may be associated to decreased hazard for childhood neoplasms (adjusted HR 0.74, 95% Cl 0.59, 0.92). Conclusions Long IPI is associated with a high hazard for childhood neoplasms, compared with intermediate and short IPIs. Short IPI may be associated with decreased hazard for childhood neoplasms.