Chronic Placental Insufficiency Research Articles

AT-rich interactive domain-containing protein 1A (ARID1A) expression in placentas with late fetal growth restriction

BACKGROUND: Fetal growth restriction, which is considered as a multifactorial pathology, is a critical problem in obstetrics. The role of mitochondrial dysfunction in the pathogenesis of fetal growth restriction is not yet clear. However, it is known that it leads to oxidative stress, damage to cells and tissues, and dysfunction of key mechanisms for maintaining energy balance, the outcome of which may be the development of placental insufficiency. It is likely that AT-rich interactive domain-containing protein 1A (ARID1A) is involved in the development and function of the human placenta and may be an important marker in the development of fetal growth restriction. AIM: The aim of this study was to evaluate ARID1A protein expression in the placental villous tree in late fetal growth restriction. MATERIALS AND METHODS: This study included 50 placentas from children born at full-term gestation (37–40 weeks). The main study group consisted of placentas with late fetal growth restriction and without major extragenital pathology (n = 35). The control group comprised 15 placentas without fetal growth restriction (n = 15). Histological (n = 50) and immunohistochemical examinations of placentas (15 placentas in the main group and 10 placentas in the control group) using primary monoclonal antibodies to ARID1A were performed. RESULTS: In the study group with fetal growth restriction, chronic placental insufficiency was verified in all cases, dissociated chronic placental insufficiency (25 cases; 71.4%) being predominant, of which 23 cases (92%) were compensated, including 16 cases (69.6%) with moderate circulatory disorders. Hypoplastic chronic placental insufficiency was diagnosed in ten cases (28.6%) and was subcompensated with the presence of pronounced circulatory disorders. In the arteries of the stem villi, the ARID1A protein expression area did not differ between the study groups (p = 0.096), while in the veins in the stem villi with fetal growth restriction, we verified a decrease compared to control (p = 0.05). In the vascular bed of the villi with subcompensated dissociated chronic placental insufficiency, ARID1A protein expression was higher compared to hypoplastic chronic placental insufficiency (p = 0.041). CONCLUSIONS: Chronic placental insufficiency combined with fetal growth restriction is a serious complication of pregnancy with the development of structural and functional abnormalities and dysregulation of placental mechanisms. The ARIDA1A protein expression data obtained, depending on the degree of compensation for chronic placental insufficiency, may indicate the activation of compensatory metabolic mechanisms to maintain the functional activity of the placenta and preserve the viability of the fetus.

Assessment of feto-placental oxygenation and perfusion in a rat model of placental insufficiency using T2* mapping and 3D dynamic contrast-enhanced MRI

IntroductionPlacental insufficiency may lead to preeclampsia and fetal growth restriction. There is no cure for placental insufficiency, emphasizing the need for monitoring fetal and placenta health. Current monitoring methods are limited, underscoring the necessity for imaging techniques to evaluate fetal-placental perfusion and oxygenation. This study aims to use MRI to evaluate placental oxygenation and perfusion in the reduced uterine perfusion pressure (RUPP) model of placental insufficiency. MethodsPregnant rats were randomized to RUPP (n = 11) or sham surgery (n = 8) on gestational day 14. On gestational day 19, rats imaged using a 7T MRI scanner to assess oxygenation and perfusion using T2* mapping and 3D-DCE MRI sequences, respectively. The effect of the RUPP on the feto-placental units were analyzed from the MRI images. ResultsRUPP surgery led to reduced oxygenation in the labyrinth (24.7 ± 1.8 ms vs. 28.0 ± 2.1 ms, P = 0.002) and junctional zone (7.0 ± 0.9 ms vs. 8.1 ± 1.1 ms, P = 0.04) of the placenta, as indicated by decreased T2* values. However, here were no significant differences in fetal organ oxygenation or placental perfusion between RUPP and sham animals. DiscussionThe reduced placental oxygenation without a corresponding decrease in perfusion suggests an adaptive response to placental ischemia. While acute reduction in placental perfusion may cause placental hypoxia, persistence of this condition could indicate chronic placental insufficiency after ischemic reperfusion injury. Thus, placental oxygenation may be a more reliable biomarker for assessing fetal condition than perfusion in hypertensive disorders of pregnancies including preeclampsia and FGR.

Prognosis of pregnancy and perinatal outcomes in the presence of polycystic ovary syndrome

Aim. To determine prognostic criteria for pregnancy complications and perinatal pathology in women with polycystic ovary syndrome.Materials and methods. A prospective study of 100 pregnant women with polycystic ovary syndrome at the St. Joasaph Belgorod Regional Clinical Hospital. Depending on the type of ART method, 2 groups were formed. The first group (n=50) of women – pregnancy occurred by induction of ovulation with chlorthyanisene clomiphene citrate (CC). The second group (n=50) – with the help of In vitro fertilisation (IVF). Research methods – clinical, laboratory, instrumental.Result. It was revealed that the main conditions for the probability of the formation of polycystic ovary syndrome and infertility are: the presence of childhood infections in the anamnesis, low birth weight of mothers. Disorders of the reproductive system in polycystic ovary syndrome (PCOS) are detected by menstrual cycle disorders, late menarche, inflammatory diseases of the genitals, primary and secondary infertility. Extragenital pathology is diagnosed in 100 % of women with PCOS and appears in the form of obesity, infectious and inflammatory diseases, infectious and inflammatory pathologies. With PCOS, miscarriage, preeclampsia, isthmic-cervical insufficiency, gestational diabetes mellitus, fetal growth retardation, chronic placental insufficiency are noted. The onset of pregnancy by stimulating ovulation of CC has an unfavorable course relative to IVF: the risk of miscarriage and isthmic-cervical insufficiency is higher. The average weight of full-term babies, the method of their birth turned out to be IVF, is greater than ovulation stimulation. The probability of perinatal damage against the background of ovulation stimulation exceeds IVF by about 1.5 times. In the early period of gestation and in conditions of PCOS, there is a hormonal imbalance: a fascination with TBG and a decrease in the secretion of PAMG in peripheral blood at 7–8 and 10–12 weeks. In women with polycystic ovary syndrome, the probability of termination of pregnancy in the first trimester is characterized by the presence of chorionitis, a decrease in the volume of the amniotic cavity, tachycardia of the embryo. Signs of placental insufficiency were detected in the II and III trimesters. In pregnant women with PCOS, hemostatic disorders are observed – a shortening of the activated recalcification time and blood clotting time and an increase in fibrinogen and prothrombin index. Pregnancy on the background of PCOS is accompanied by activation of free radical oxidation and the development of oxidative stress.Conclusion. To predict placental insufficiency, the risk of miscarriage, perinatal pathology of the nervous system in pregnant women with PCOS, it is necessary to assess the level of glycodelin, TBG, PAMG‑1, β-HCG.

Changes in the blood flow in the uterine and umbilical arteries during the second trimester of pregnancy in exacerbation of bronchial asthma associated with reactivation of cytomegalovirus infection

Aim. To evaluate changes in blood flow in the uterine and umbilical arteries in the second trimester of gestation in women with exacerbation of bronchial asthma associated with reactivation of cytomegalovirus infection (CMVI).Materials and methods. Using Doppler analysis, 115 patients were examined at 21-24 weeks of pregnancy, uncomplicated and complicated by exacerbation of mild to moderate asthma of cytomegalovirus etiology. The first group was represented by 30 seronegative women with uncomplicated pregnancy. The second group included 30 patients with mild asthma in the stage of exacerbation associated with CMVI, leading to chronic compensated placental insufficiency. The third group consisted of 30 patients with exacerbation of moderate asthma caused by CMVI reactivation, which initiated the development of chronic compensated placental insufficiency. The fourth group consisted of 25 women with moderate asthma in the acute stage against the background of the acute phase of CMVI, leading to the formation of chronic subcompensated placental insufficiency.Results. In women in the second group, in comparison with the first group, the following changes were determined: in the right uterine artery, the systolic-diastolic ratio (SDR) was, respectively, 2.75±0.07 and 2.04±0.03 rel. units (р<0.001), pulsation index (PI) – 1.15±0.04 and 0.76±0.02 rel. units (p<0.001), resistance index (RI) – 0.63±0.01 and 0.51±0.01 rel. units (p<0.001); in the left uterine artery, SDR was, respectively, 2.84±0.09 and 1.98±0.05 rel. units (p<0.001), PI – 1.20±0.05 and 0.74±0.03 rel. units (p<0.001), RI – 0.64±0.01 and 0.49±0.01 rel. units (p<0.001); in the absence of statistically significant differences in the indicators of SDR in the umbilical artery – 3.62±0.09 and 3.41±0.06 rel. units, respectively (р>0.05), PI – 1.23±0.03 and 1.19±0.03 rel. units (p>0.05) and RI – 0.73±0.01 and 0.70±0.01 rel. units (p>0.05). In the third group, in comparison with the second one, vascular resistance did not differ significantly in the right, left uterine arteries and the umbilical cord artery. In patients of the fourth group, in contrast to the third one, higher values of resistance to blood flow were observed: in the right uterine artery – SDR (3.41±0.07 and 2.87±0.07 rel. units, p<0.001), PI (1.48±0.07 and 1.18±0.03 rel. units, p<0.001), RI (0.70±0.01 and 0.65±0.01 relative units, p<0.001); in the left uterine artery – SDR (3.33±0.11 and 2.88±0.09 rel. units, p<0.01), PI (1.45±0.05 and 1.19±0.05 rel. units, p<0.001), RI (0.70±0.01 and 0.68±0.01 rel. units, p<0.01); and also in the umbilical artery – SDR (4.39±0.13 and 3.65±0.12 rel. units, p<0.001), PI (1.45±0.04 and 1.24±0.03 rel. units, p<0.001), RI (0.79±0.01 and 0.72±0.01 rel. units, p<0.001).Conclusion. In the pathogenesis of reduced blood flow in the basin of the uterine and umbilical arteries in women with exacerbation of moderately severe asthma of cytomegalovirus etiology, leading to the development of chronic subcompensated placental insufficiency, compared with uterine cord hemodynamics in asthma in the acute stage, caused by reactivation of CMVI in the second trimester of gestation, which initiates the formation of a chronic compensated form of placental dysfunction in the third trimester of pregnancy, an important role is played by viral stimulation of vasoconstrictor responses.

Changes in immunity during the second trimester of pregnancy in women with exacerbation of bronchial asthma associated with reactivation of cytomegalovirus infection

Aim. To evaluate changes in immunity in the second trimester of pregnancy in women with exacerbation of bronchial asthma associated with reactivation of cytomegalovirus infection (CMVI).Materials and methods. The concentration of secretory immunoglobulin A (sIgA), immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM) and circulating immune complexes (CIC) was studied in 112 women at 21-24 weeks of uncomplicated pregnancy and pregnancy complicated by exacerbation of mild-to-moderate asthma associated with CMVI. The first group included 30 women seronegative for CMV, with an uncomplicated pregnancy. The second group consisted of 30 patients with exacerbation of mild asthma, initiated by the acute phase of CMVI, which induces the development of chronic compensated placental insufficiency. The third group consisted of 27 patients with moderate asthma in the acute stage against the background of the acute phase of CMVI, leading to the formation of chronic compensated placental insufficiency. The fourth group included 25 patients with exacerbation of moderate asthma with CMV etiology, initiating the development of chronic subcompensated placental insufficiency.Results. In women of the second group, the concentration of sIgA was 5.91±0.371 mg/L, IgA – 2.64±0.089 mg/mL, IgG – 15.4±0.791 mg/mL, IgM – 2.32±0.144 mg/mL, CIC – 0.176±0.004 optical density units (in the first group, respectively, 4.31±0.266 mg/L, p<0.001; 2.37±0.06 mg/mL, p<0.05; 13.3±0.293 mg/mL, p<0,05; 1.11±0.06 mg/mL, p<0.001; 0.092±0.005 optical density units, p<0.001). In patients of the third group, in contrast to the second one, no differences in immunity parameters were detected. In the fourth group, in comparison with the third one, lower parameters of sIgA (3.21±0.213 mg/L, p<0.001), IgA (1.43±0.081 mg/mL, p<0.001), as well as higher IgG values were detected (19.8±0.418 mg/mL, p<0.001), IgM (2.94±0.082 mg/mL, p<0.01) and CIC (0.198±0.005 optical density units, p<0.05).Conclusion. In patients with moderate asthma with exacerbation against the background of CMVI reactivation, which initiates the formation of chronic subcompensated placental insufficiency, in contrast to women with moderate asthma in the stage of CMVI exacerbation in the second trimester of pregnancy, leading to chronic compensated placental insufficiency in the third trimester of gestation, a more pronounced imbalance of humoral immunity and autoimmune disorders are found, which are important in the development of chronic placental dysfunction.

Changes in the cytokine status in women with exacerbation of bronchial asthma due to reactivation of cytomegalovirus infection in the second trimester of pregnancy

Aim. To study changes in the cytokine status in women with exacerbation of bronchial asthma caused by reactivation of cytomegalovirus infection (CMVI) in the second trimester of gestation.Materials and methods. The concentration of pro-inflammatory cytokines (TNFα, IL-1β, IFNγ, IL-2) in blood serum was assessed in 112 women in the second trimester of pregnancy, uncomplicated and complicated by exacerbation of asthma caused by reactivation of CMVI. The first group included 30 women seronegative for CMVI with uncomplicated pregnancy. The second group consisted of 30 patients with exacerbation of mild asthma associated with CMVI, initiating the formation of chronic compensated placental insufficiency. The third group consisted of 27 patients with exacerbation of moderate asthma induced by CMVI reactivation leading to the development of chronic compensated placental insufficiency. The fourth group included 25 women with exacerbation of moderate asthma due to the acute phase of CMVI, which induces the development of chronic subcompensated placental insufficiency.Results. It was found that in the blood serum of women of the first group, the concentration of TNFα was (Me) 21.5 (13.8–30.1) pg/mL, IL-1β – 18.2 (13.6–34.0) pg/mL, IFNγ – 137.4 (109.5‒174.2) pg/mL and IL-2 – 29.8 (21.0‒38.9) pg/mL. In patients of the second group, compared with the first one, there was an increase in the level of TNFα by 3.79 times (p=0.000001), IL-1β – by 4.8 times (p=0.000001), IFNγ – by 1.73 times (p=0.000001) and IL-2 by 2.91 times (p=0.000001). In the third group, unlike the second one, no significant differences were found between the concentrations of TNFα, IL-1β, IFNγ, and IL-2. In patients of the fourth group, in comparison with the third group, higher values of TNFα (1.35 times, p=0.00507), IL-1β (1.86 times, p=0.000001), IFNγ (1.31 times, p=0.000167), and IL-2 (1.5 times, p=0.0056) were registered.Conclusion. During exacerbation of moderate asthma of cytomegalovirus etiology, leading to chronic subcompensated placental insufficiency, in comparison with exacerbation of moderate asthma caused by reactivation of CMVI, initiating the formation of chronic compensated placental insufficiency, activation of the systemic inflammatory response is most pronounced, leading to stimulation of the migration of monocytes, lymphocytes and neutrophils to the focus of inflammation at the level of small bronchi; also leading to disruption of intersystem relationships and to hemodynamic dysfunction of the placenta.

Course of pregnancy, delivery, the state of the fetoplacental complex in women with abdominal obesity and hypertensive disorders

Maternal obesity is becoming more common, occurring in one third of pregnant women, and is associated with increased morbidity and mortality in both mothers and children. The article presents data from a study of the course of pregnancy and childbirth in women with abdominal obesity. It was found that a third of women with abdominal obesity had signs of placental insufficiency on Doppler ultrasound (OR=2,9; 95% CI 1,2; 6,6, p<0,05), chronic placental insufficiency was more often recorded (20 (22,2%); TCP=0,03, p<0,05) and gestational diabetes mellitus (14 (15,6%), TCP=0,005, p<0,05). Childbirth in women with abdominal obesity was complicated by the development of decompensated placental insufficiency (15 (16,7%), p<0,05), and weakness of labor activity (13 (14,4%), p<0,05).

A Study of the Literature on Intrauterine Treatment Options for Chronic Placental Insufficiency with Intrauterine Growth Restriction Using Intrauterine Intravascular Amino Acid Supplementation.

Intrauterine growth retardation (IUGR) is a very serious prenatal condition with 3-5% incidence of all pregnancies. It results from numerous factors, including chronic placental insufficiency. IUGR is associated with an increased risk of mortality and morbidity and is considered a major cause of fetal mortality. Currently, treatment options are significantly limited and often result in preterm delivery. Postpartum, IUGR infants also have higher risks of disease and neurological abnormalities. The PubMed database was searched using the keywords "IUGR", "fetal growth restriction", "treatment", "management" and "placental insufficiency" for the period between 1975 and 2023. These terms were also combined together. There were 4160 papers, reviews and articles dealing with the topic of IUGR. In total, only 15 papers directly dealt with a prepartum therapy of IUGR; 10 of these were based on an animal model. Overall, the main focus was on maternal intravenous therapy with amino acids or intraamniotic infusion. Treatment methods have been tested since the 1970s to supplement the fetuses with nutrients lacking due to chronic placental insufficiency in various ways. In some studies, pregnant women were implanted with a subcutaneous intravascular perinatal port system, thus infusing the fetuses with a continuous amino acid solution. Prolongation of pregnancy was achieved, as well as improvement in fetal growth. However, insufficient benefit was observed in infusion with commercial amino acid solution in fetuses below 28 weeks' gestation. The authors attribute this primarily to the enormous variation in amino acid concentrations of the commercially available solutions compared with those observed in the plasma of preterm infants. These different concentrations are particularly important because differences in the fetal brain caused by metabolic changes have been demonstrated in the rabbit model. Several brain metabolites and amino acids were significantly decreased in IUGR brain tissue samples, resulting in abnormal neurodevelopment with decreased brain volume. There are currently only a few studies and case reports with correspondingly low case numbers. Most of the studies refer to prenatal treatment by supplementation of amino acids and nutrients to prolong pregnancy and support fetal growth. However, there is no infusion solution that matches the amino acid concentrations found in fetal plasma. The commercially available solutions have mismatched amino acid concentrations and have not shown sufficient benefit in fetuses below 28 weeks' gestation. More treatment avenues need to be explored and existing ones improved to better treat multifactorial IUGR fetuses.

Serotonin and cyclic sleep organization in full-term newborn infants with intrauterine growth retardation

BACKGROUND: The high frequency of neurological and mental diseases in children who had intrauterine retardatiojn development indicates the need to study specific markers of disorders of fetal brain functional development, in particular, the state of the serotonergic system, which plays a key role in the morpho-functional development of the brain in early ontogenesis.
 AIM: To study the content of serotonin in full-term newborns with intrauterine development delay in comparison with quantitative and qualitative characteristics of sleep.
 MATERIALS AND MЕTHODS: The main group consisted of 26 newborns, whose intrauterine development took place in conditions of chronic placental insufficiency, which led to the formation of an asymmetric form of intrauterine retardatiojn development. The control group consisted of 72 healthy newborns from healthy mothers without pregnancy complications. Children of each group are divided into three subgroups depending on gestational age: I 37, II 38, III 3940 weeks. In all children, 712 hours after birth, an electropoligram of sleep was recorded (an electroencephalograph of the company Mizar, Russia) and its quantitative and qualitative analyses were carried out, highlighting the orthodox, paradoxical phase and undifferentiated state. The serotonin content was determined in platelet-rich plasma of blood from the umbilical cord vein after birth, as well as in a platelet suspension prepared from venous blood taken on the first day of life. The content of serotonin in platelets was judged by the indicator obtained by dividing the amount of serotonin in the platelet suspension by the platelet level. The amount of serotonin was determined by high-performance liquid chromatography with electrochemical detection. Statistical analysis was performed using the Statistica 6 program (Statsoft Inc, USA).
 RESULTS: We report here a low content of serotonin in platelet-rich plasma and platelets of newborns with intrauterine growth retardation and the absence of its normal increase in weeks 3739 of intrauterine development, as well as a violation of the genetic programming for the sleep-wake cycle organization.
 CONCLUSIONS: Assessment of the serotonin-producing system of the brain in comparison with the newborn sleep pattern can serve as a diagnostic marker of brain damage and substantiate the need for timely application of neuroprotection.

Задержка роста плода: современные критерии диагностики, тактика ведения беременности и родов

Objective. To prove the advantages of new diagnostic criteria for fetal growth restriction (FGR) with centile assessment of fetal biometric parameters and Doppler parameters of blood flow in the maternal-placental-fetal system. Patients and methods. A retrospective analysis was made of 364 obstetric histories and perinatal outcomes in patients diagnosed with FGR during pregnancy according to the “former” classification. Simultaneously, fetal growth was assessed using the new classification (2022); a comparative analysis of the diagnostic significance of FGR criteria in both classifications was performed. The prospective phase involved 90 patients in whom the diagnosis of FGR was based on the centile assessment of fetal biometric parameters and Doppler parameters. The examination included Doppler ultrasound and computerized cardiotocography. The histological examination of the placenta was carried out in 23 cases of FGR. Results. The use of new diagnostic criteria for FGR based on the centile assessment of fetal biometric parameters and Doppler parameters significantly reduced the rate of false-positive diagnoses of FGR from 40% to 15%. The histological examination of 21 (82%) out of 23 placentas revealed chronic placental insufficiency with equal frequency in the early (32%) and late (37%) phenotype of FGR. Conclusion. Thus, the use of new diagnostic criteria for FGR can improve the fetal growth assessment and optimize pregnancy and labor management tactics, accompanied by a decrease in the rate of unjustified preterm labor, cesarean sections, and improved perinatal outcomes. Key words: fetal growth restriction, classification of fetal growth restriction, small for gestational age

МОРФОФУНКЦИОНАЛЬНЫЕ ОСОБЕННОСТИ ПЛАЦЕНТЫ ПРИ ТУБЕРКУЛЁЗЕ ВО ВРЕМЯ БЕРЕМЕННОСТИ

Objective: To study the morphology of the placenta in pregnant women with TB Methods: The morphology of the 26 placentas was evaluated in this study, out of which 15 were from women with various forms and localizations of TB (main group), while 11 were from healthy pregnant women (control group). The placentas were evaluated macroscopically. Central and peripheral zones of the placenta and umbilical cord were sampled and embedded in paraffin. Histological slides were stained with hematoxylin-eosin and examined using an Olympus CX-21 microscope with a Universal Infinity Optical System (UIS2). Results: Women in the main group were significantly more commonly underweight (p<0.01) compared to the control group. They also showed a significantly higher frequency of decompensated chronic placental insufficiency (PI), increased share of immature intermediate differentiated villi, dystrophic and degenerative changes in the placenta (foci of dystrophic calcification, afunctional syncytial nodules), and circulatory disorders (ischemic necrosis, fibrinoid in the intervillous space). Foci of calcification and infarctions in the villi embedded in fibrinoid were also significantly more common in the main group. Compensatory changes included pronounced angiomatosis, hypervascularization of villi, an increase in the number of terminal villi, the formation of synticiocapillary membranes, and functional syncytial nodules Conclusion: TB in pregnant women leads to morphological and functional changes in the placenta (delayed villous maturation, disorders of the uteroplacental circulation) and the development of more severe forms of chronic PI. The compensatory changes in the placenta might not sustain the required level of its blood supply, which results in deterioration of the perinatal outcomes (intrauterine growth restriction – IUGR).

Morphological structure of cotyledons with non-contrasted blood vessels in the placenta of women who had an exacerbation of mono- and mixed-cytomegalovirus infection in the second trimester of pregnancy

Aim. To assess the morphological structure of cotyledons with non-contrasted blood vessels in the pla­centas in women who had an exacerbation of mono- and mixed cytomegalovirus infection (CMVI) in the second trimester of pregnancy.Materials and methods. The histometric parameters of the villi were studied with different visualization on X-ray phlebograms of blood vessels in 112 cotyledons of placentas in women with pregnancy, uncomplicated and com­plicated by mono- and mixed-CMVI (combination of CMVI and reactivation of chronic herpes virus infection type 1 HSV). The first group (control) included 36 cotyledons with a clear contrasting of the vascular bed in the placentas from women with an uncomplicated gestational period. The main group was represented by 76 cotyledons: subgroup 2a - 24 cotyledons, in which the bloodstream was not detected, in placentas from patients with exacerbation of mono-CMVI as­sociated with chronic subcompensated placental insufficiency (CSPI); subgroup 2b - 16 cotyledons with blood vessels not diagnosed by X-ray phlebography, in placentas from women with mixed CMVI infection, initiating the development of CSPI; subgroup 3a - 21 cotyledons with non-contrasted bloodstream in placentas from patients with exacerbation of mono-CMVI and chronic decompensated placental insufficiency (CDPI); subgroup 3b - 15 cotyledons with a similar an­giographic picture in placentas from women who had an exacerbation of mixed CMVI in the second trimester of gestation and CDPI. Identification of cotyledons with a clear visualization of blood vessels and with a non-contrasted vascular bed in the marginal part of the placenta was carried out by dosed administration of minium on linseed oil (1:3) through the vein of umbilical cord and assessment of the angiographic picture on X-ray, which were obtained using the RUM-20M apparatus with X-ray image amplifier Sapphire (Russia). For histological analysis, tissue pieces were taken in the same places before and after injection of the contrast mass into the bloodstream of the organ, on the damaged areas of which clamps were applied.Results. In the first group, the cotyledons had clear contours of the blood vessels and the vein draining them. Avascular villi (AV) accounted for 2.05±0.22%, villi with syncytiocapillary membranes (SCM) - 33.5±2.41%, villi with one (1) SCM - 77.1±2.07%, with two (2) SCM - 20.9±1.98% and with three (3) SCM - 1.42±0.09%. In subgroup 2a, compared with the first group, there was a deformation of the lumen of the vein of the stem villi of the I and II order, in which erythrocyte aggregates, single leukocytes and rarely thrombi were determined, as well as signs of edema and partial desquamation of endotheliocytes, fibrinoid and inflammatory changes in the vessel wall. The number of AV increased (by 6.87 times, p<0.001) and the number of villi with SCM decreased (by 2.05 times, p<0.001) with no significant differences between villi with 1, 2, and 3 SCM. In subgroup 2b, in comparison with subgroup 2a, mod­erate folding of the endothelium, areas of its partial desquamation, AV (1.39 times, p<0.01) and villi with 2 SCMs (1.44 times, p<0.05) were more common against the background of a decrease in the concentration of villi with 1 SCM (by 1.19 times, p<0.05). In subgroup 3b, a greater number of vessels were found that did not provide outflow of blood from cotyle­dons (12, p<0.001) and had an arcuate shape (10, p<0.001) compared with subgroup 3a, where their number was, respec­tively, 3 (p<0.001) and 2 (p<0.001). A more pronounced folding of the endothelial lining was determined, as well as ag­gregates, neutrophils, lymphocytes and thrombi in the lumen of the vessels. There was an increase in the percentage of villi with 1 SCM (by 1.13 times, p<0.05), as well as a decrease in the frequency of occurrence of villi with 2 SCM (by 1.67 times, p<0.05) and 3 SCM (by 2.13 times, p<0.001). In cotyledons of subgroup 3b, in contrast to those of subgroup 2b, blindly ending vessels were more common (2 times, p<0.05), arcuate course of veins (2.5 times, p<0.05), lumen de­formity, hyperchromia of the nucleus and total desquamation of cells, thrombi with calcification, complete and partial obliteration of the arterial lumen, inflammation, fibrinoid degradation of the muscular layer of vessels and the deposition of calcium salts in it, as well as AV (1.29 times, p<0.05) and villi with 1 SCM (1.40 times, p<0.001); less often villi were detected with SCM (1.35 times, p<0.05), with 2 SCM (2.78 times, p<0.001) and 3 SCM (1.57 times, p<0.05).Conclusion. In women with exacerbation of mixed CMVI in the second trimester of gestation and CDPI, in contrast to patients with reactivation of mono-CMVI leading to CDPI, angiodestructive and angioobstructive processes, as well as inhibition of angiogenesis, are more pronounced in cotyledons with non-visualized blood vessels. This increases vascular resistance and blocks the flow of the contrast mass during its dosed injection into the vascular bed of the placenta.

Immuno-hormonal and dopplerometric characteristics of placental insufficiency in pregnant women with exacerbation of chronic bronchitis associated with reactivation of cytomegalovirus infection

Aim. To give immune-hormonal and dopplerometric characteristics of placental insufficiency in pregnant women with exacerbation of chronic bronchitis associated with reactivation of cytomegalovirus infection (CMVI).Ma­terials and methods. The concentration of IL-ie, IL-2 and progesterone was studied in the blood serum, and the pulsation index (PI) in the right uterine artery (RUA) was determined in 80 patients at 21-24 weeks of gestation, uncomplicated and complicated by exacerbation of chronic simple bronchitis due to reactivation of CMVI. In a retrospective analysis, 3 groups were formed. The first group - 30 women with CMV-seronegative physiological pregnancy; the second - 25 patients with chronic bronchitis in the acute stage, initiated by the acute phase of CMVI, leading to chronic compensated placental in­sufficiency (CCPI); the third - 25 women with exacerbation of chronic bronchitis CMVI etiology, causing the development of chronic subcompensated placental insufficiency (CSPI) in the third trimester of gestation.Results. In the first group, the concentration of IL-ie was 22.8±0.02 pg/mL, IL-2 - 30.6±2.34 pg/mL, progesterone - 130.8±8.19 nmol/L, and the value of PI in RUA - 0.83±0.04 rel. units. In patients of the second group, compared with the first, the level of IL-ie in­creased by 3.82 times (p<0.00i), IL-2 - by 2.55 times (p<0.00i) and PI in the RUA - by i.40 times (p<0.00i) against the background of a decrease in the progesterone concentration by i.47 times (p<0.00i). The third group compared with the first was characterized by an increase in the concentration of IL-ie by 6.87 times (p<0.001), IL-2 - by 3.19 times (p<0.001) and PI in RUA by i.66 times (p<0.00i) with lower levels of progesterone (i.93 times, p<0.00i). In the third group, in contrast to the second one, an increase in IL-ie was observed by 1.79 times (p<0.001), IL-2 - by 1.24 times (p<0.05) and PI in RUA - by i.i7 times (p<0.05), as well as a decrease in progesterone levels by i.3i times (p<0.0i). There was an in­crease in the relationship of PI in RUA with the concentration of IL-ie (r=0.69; p<0.001), IL-2 (r=0.75; p<0.001) and progesterone (r=-0.55; p<0.01).Conclusion. A more pronounced systemic inflammatory reaction, leading to inhibition of progesterone synthesis and increased resistance to blood flow at RUA develops in exacerbation of chronic bronchitis in the second trimester of gestation against the background of reactivation of CMVI, which initiates the development of CCPI, in comparison with the exacerbation of bronchopulmonary pathology of a similar etiology, which determines the formation of subsequent CCPI.

Excitatory and inhibitory neuron imbalance in the intrauterine growth restricted fetal guinea pig brain: Relevance to the developmental origins of schizophrenia and autism.

Neurodevelopmental disorders such as schizophrenia and autism are thought to involve an imbalance of excitatory and inhibitory signaling in the brain. Intrauterine growth restriction (IUGR) is a risk factor for these disorders, with IUGR onset occurring during critical periods of neurodevelopment. The aim of this study was to determine the impact of IUGR on excitatory and inhibitory neurons of the fetal neocortex and hippocampus. Fetal brains (n=2) were first collected from an unoperated pregnant guinea pig at mid-gestation (32days of gestation [dg]; term ∼67dg) to visualize excitatory (Ctip2) and inhibitory (calretinin [CR] and somatostatin [SST]) neurons via immunohistochemistry. Chronic placental insufficiency (CPI) was then induced via radial artery ablation at 30dg in another cohort of pregnant guinea pigs (n=8) to generate IUGR fetuses (52dg; n=8); control fetuses (52dg; n=7) were from sham surgeries with no radial artery ablation. At 32dg, Ctip2- and CR-immunoreactive (IR) cells had populated the cerebral cortex, whereas SST-IR cells had not, suggesting these neurons were yet to complete migration. At 52dg, in IUGR versus control fetuses, there was a reduction in SST-IR cell density in the cerebral cortex (p=.0175) and hilus of the dentate gyrus (p=.0035) but not the striatum (p>.05). There was no difference between groups in the density of Ctip2-IR (cortex) or CR-IR (cortex, hippocampus) neurons (p>0.05). Thus, we propose that an imbalance in inhibitory (SST-IR) and excitatory (Ctip2-IR) neurons in the IUGR fetal guinea pig brain could lead to excitatory/inhibitory dysfunction commonly seen in neurodevelopmental disorders such as autism and schizophrenia.

Perinatal outcomes of pregnancy and childbirth in moderate to severe COVID-19 patients

BACKGROUND: The presence of COVID-19 caused by SARS-CoV-2 during pregnancy increases the incidence of adverse perinatal outcomes, which are manifested in more frequent spontaneous miscarriages, premature births, antenatal fetal deaths, and fetal growth retardation, as well as in the development of intraamniotic infection and respiratory distress syndrome of the newborn. The most likely cause of premature birth can be considered severe respiratory failure of the mother with hypoxemia, which leads to circulatory disorders in the hemodynamic system of the mother-placenta-fetus. Currently, there is no single expert opinion on pregnancy prolongation tactics, as well as the timing and methods of delivery in patients with COVID-19, which is decided individually by an interdisciplinary consultation of the experts, taking into account the severity of the patients condition, gestational age and fetal condition.
 AIM: The aim of this study was to analyze perinatal outcomes of pregnancy and childbirth in the presence of moderate and severe COVID-19.
 MATERIALS AND METHODS: We carried out a retrospective analysis of perinatal outcomes in patients with the novel coronavirus infection in a specialized level III infectious hospital in St. Petersburg, Russia in 20202021 (from the first to the fourth wave of COVID-19) based on the birth histories of 50 patients with moderate (n = 31) and severe (n = 19) forms of the disease.
 RESULTS: Most of the patients suffered from chronic somatic diseases, with the course of pregnancy and childbirth complicated by premature rupture of amniotic fluid and progressive fetal hypoxia (fetal distress). In severe COVID-19, preterm labor prevailed and the proportion of operative abdominal delivery more than doubled that of vaginal delivery. The course of the postpartum period was determined by the COVID-19 positive dynamics. The majority of patients in the study groups showed significant changes in laboratory parameters such as anemia, an increase in the level of neutrophilic leukocytes with a subsequent decrease in their count, lymphopenia followed by lymphocytosis, and an increase in the levels of C-reactive protein and the activities of lactate dehydrogenase, alanine aminotransferase and aspartate aminotransferase. The study of the relationship between the most characteristic laboratory parameters in the disease dynamics showed the presence of statistically significant correlations between inflammation markers and metabolic markers, which allowed for assessing the severity of the patients condition.
 Antenatal diagnosis of the fetal functional status based on cardiotocography, ultrasound and Doppler sonography data revealed a predominantly compensated fetal condition in the study groups. The condition of newborns in all patients with moderate COVID-19 and in most of patients with the severe form of the disease was satisfactory. In severe COVID-19, the birth of children with moderate asphyxia was due to prematurity and antenatal hypoxia resulted from decompensation of chronic placental insufficiency. The histopathological patterns of the afterbirth in the study groups were represented by inflammatory changes and chronic placental insufficiency.
 CONCLUSIONS: The data obtained suggest that the basis for favorable perinatal outcomes is an adequate assessment of the condition of the pregnant woman and the fetus with timely delivery before the onset of irreversible organ damage.

Pathomorphological characteristics of cotyledons with weak contrasting of the blood flow in the placenta of women who have undergone exacerbation of cytomegalovirus infection during the second trimester of pregnancy

Aim. To give pathomorphological characteristics of placental cotyledons with weakly contrasted bloodstream in women who had an exacerbation of cytomegalovirus infection (CMVI) in the second trimester of pregnancy.Materials and methods. A study was made of involutive-destructive processes in 153 cotyledons of the placenta with well and weakly contrasted bloodstream in women with pregnancy, uncomplicated and complicated by exacerbation of CMVI at 21-24 weeks of gestation. The first group included 36 cotyledon placentas from women with CMV-seronegative uncomplicated pregnancy with well contrasted blood vessels; the second group – 67 cotyledon placentas from patients with chronic compensated placental insufficiency (CCPI) and poorly contrasted vascular network; the third group – 30 cotyledon placentas from women with chronic subcompensated placental insufficiency (CSPI) with indistinctly visualized blood vessels; the fourth group – 20 cotyledon placentas from patients with chronic decompensated placental insufficiency (CDPI). Dosed introduction of red lead on drying oil (1:3) into the blood vessels of the placenta was carried out through the umbilical cord vein. Obtaining X-ray images of cotyledons with well and weakly contrasted blood vessels in the marginal part of the organ was carried out on the apparatus RUM-20M with X-ray image intensifier Sapphire (Russia). Cotyledon biopsy specimens for histometry and histochemical analysis were taken before their contrasting, and for survey microscopy – after injection of the contrast mass.Results. In the first group, the amount of fibrinoid in the stroma of the villi was 1.35±0.09%, perivillous fibrinoid − 1.02±0.08% in the absence of pseudonecrosis and calcifications. In the second group, unlike the first one, cotyledons prevailed, in which in 40-50% of cases weakly expressed contours of blood vessels were found, an increase in the specific volume of stromal fibrinoid by 1.82 times was observed (p<0.001), and fibrinoid around villi by 2.04 times (p<0.001); pseudonecrosis accounted for 2.29±0.13%, and calcificates − 1.50±0.12%. In the third group, in comparison with the second one, cotyledons were more common with 50-70% of indistinctly contoured vessels, villi with edematous changes and stromal collagenization; the concentration of stromal fibrinoid increased by 1.47 times (p<0.001), the proportion of perivillous fibrinoid – 1.46 times (p<0.001), pseudonecrosis – 1.41 times (p<0.001) and the accumulation of calcium salt – 1.57 times (p<0.001). In the fourth group, compared to the third one, cotyledons were more common, in which more than 70% of weakly contrasted blood vessels were determined, while the number of collagen fibers and acid glycosaminoglycans increased in the villi; there was an increase in the amount of fibrinoid around the villi by 1.24 times (p<0.01), pseudonecrosis – by 1.23 times (p<0.05) and calcificates – by 1.32 times (p<0.01).Conclusion. In women with an exacerbation of CMVI in the second trimester of gestation and CSPI, in contrast to patients with a similar infectious disease and CCPI, a decrease in the flow of contrast into the bloodstream of cotyledons is due to more pronounced edema, the formation of collagen fibers, fibrinoid and calcium salts in the stroma of the villi, as well as perivillous fibrinoid. In CDPI of cytomegalovirus etiology, compared with CSPI, weak contrasting of the vascular bed of cotyledons is associated with increasing changes in the stroma involved in the regulation of the resistance of draining veins and intracotyledon blood vessels.

Changes in immunological parameters and umbilical blood flow in pregnant women during exacerbation of chronic bronchitis associated with cytomegalovirus infection

Aim. To evaluate changes in immunological parameters and umbilical blood flow in pregnant women with exacerbation of chronic bronchitis associated with cytomegalovirus infection (CMVI).Materials and methods. The concentration of secretory immunoglobulin A (sIgA), immunoglobulin E (IgE), circulating immune complexes (CIC), interleukin- 6 (IL-6), interleukin-4 (IL-4) and systolic-diastolic ratio (SDR) in the umbilical artery was studied in 80 women with exacerbation of chronic bronchitis in the second trimester of pregnancy, uncomplicated and complicated by the acute phase of CMVI. The first group was represented by 30 women with cytomegalovirus seronegative physiological pregnancy; the second – 25 patients with exacerbation of chronic bronchitis caused by reactivation of CMVI, complicated by the development of chronic compensated placental insufficiency (CCPI); the third – 25 women with chronic simple bronchitis in the acute stage in the setting of the acute phase of CMVI, initiating the formation of chronic subcompensated placental insufficiency (CSPI) at 30-34 weeks of gestation.Results. In the first group, the concentration of sIgA in blood serum was 4.3±0.26 mg/L, IgE – 3.64±0.23 IU/mL, CIC – 0.091±0.005 AU, IL-6 – 2.41±0.21 pg/mL, IL-4 – 30.1±2.19 pg/mL, cortisol – 527.2±20.95 nmol/L, and SDR in the artery umbilical cord – 3.41±0.06 relative units. In women of the second group, in comparison with the first one, there was an increase in the concentration of sIgA by 1.40 times (p<0.01), IgE – by 1.95 times (p<0.001), CIC – by 1.83 times (p<0.001) , IL-6 – 2.61 times (p<0.001), IL-4 – 1.29 times (p<0.05), cortisol – 1.35 times (p<0.001) in the absence of statistically significant differences the magnitude of vascular resistance in the umbilical artery. In the third group, in comparison with the first one, there was a decrease in sIgA values by 1.26 times (p<0.05) in the setting of an increase in the concentration of IgE by 2.56 times (p<0.001), CIC – by 2.09 times (p<0.001 ), IL-6 – by 3.65 times (p<0.001), IL-4 – by 1.64 times (p<0.001), cortisol – by 1.52 times (p<0.001) and SDR in the umbilical artery – 1.27 times (p<0.001). In women of the third group, in contrast to the second one, a decrease in the concentration of sIgA by 1.77 times (p<0.001), as well as an increase in IgE by 1.31 times (p<0.01), CIC ‒ by 1.14 times (p<0.001), IL-6 ‒ 1.39 times (p<0.001), IL-4 ‒ 1.27 times (p<0.05), cortisol ‒ 1.13 times (p<0.05) and SDR in the umbilical artery ‒ 1.21 times (p<0.001). A direct correlation was established between IL-6 and cord blood flow (r=0.53; p<0.01), as well as an inverse relationship between sIgA and cortisol (r=-0.44; p<0.05).Conclusion. In the second trimester of gestation, exacerbation of chronic simple bronchitis caused by reactivation of CMVI, which initiates the development of CSPI, in contrast to chronic bronchitis in the acute stage, associated with the acute phase of chronic CMVI, which induces the formation of CCPI, is accompanied by an imbalance of nonspecific local and systemic immune responses, as well as stress-reaction, which leads to the growth of SDR in the umbilical artery.

Features of the course and management of pregnant patients with COVID-19

Objective . To assess the effectiveness of the treatment of pregnant patients with moderate COVID-19 pneumonia. Materials and methods . A dynamic prospective study of the course of pregnancy in the second and third trimesters was carried out in 36 female patients with moderate COVID-19 pneumonia undergoing treatment at the Department of Obstetrics and Observation of Gomel City Clinical Hospital No.3. The comparison groups consisted of 30 pregnant patients without COVID-19 and 30 female patients of childbearing age with moderate COVID-19 pneumonia. All pregnant patients with pneumonia received treatment with the antiviral drug «Remdesivir», all non-pregnant patients underwent clinical treatment without antiviral drugs. Results . The study has found no significant differences in the frequency of gynecological and obstetric pathology in the anamnesis between the groups of the pregnant patients. However, the pregnant patients with pneumonia were characterized by comorbidity (anemia, chronic pyelonephritis, obesity). The main clinical symptoms in the patients with pneumonia did not differ significantly and were related to adaptive changes to pregnancy. The pregnant patients with pneumonia showed more rapid normalization of body temperature, oxygen dependence, and laboratory parameters. The remdesivir treatment for pneumonia did not lead to any progression of obstetric complications of pregnancy (thereatened miscarriage, chronic placental insufficiency) or development of any other complications. All the patients were discharged from the hospital with progressing pregnancy. Conclusion . High efficiency of the treatment of pregnant patients with moderate pneumonia using the complex therapy with the antiviral drug «Remdesivir» has been shown. It leads to a rapid enhancement of clinical and laboratory parameters in patients, but does not affect the duration of the treatment. The absence of direct adverse side effects and complications of pregnancy makes it reasonable to use this drug in the complex therapy of moderate pneumonia in the second and third trimesters. It is necessary to continue this study to analyze the long-term treatment results.

ВЕДЕНИЕ БЕРЕМЕННОСТИ У ВИЧ-ПОЗИТИВНЫХ ЖЕНЩИН

The article describes the management of HIV-positive pregnant women. It was shown that pregnancy complications in these women were observed more often in the second trimester of pregnancy. At the same time, the incidence of gestosis, anemia and chronic placental insufficiency decreases against the background of specific antiviral therapy.

Intraventricular hemorrhages in premature newborns: predictors of development

Intraventricular hemorrhage is the most common type of brain damage in infants with extremely low and very low body weight. The main source of intraventricular hemorrhages in premature infants are the vessels of the ventricular germinal zone, or germ matrix. Intraventricular hemorrhages are caused by many risk factors. The current concept is that predictors of development are classified into ante-, intra- and postnatal. The most significant among them is intrauterine infection, which can have a direct and indirect effect on the immature structures of the fetal brain. Also of great importance are the concomitant pathology of the cardiovascular system in the mother and complications of pregnancy and childbirth (placental abruption, rapid delivery, chronic placental insufficiency). On the part of the newborn, coagulation disorders in combination with immaturity of the hemostatic system, as well as pathology of the cardiovascular and respiratory systems are important. Predictors of intraventricular hemorrhages in premature infants (genetic, hemostasiological, morphological), require further study, analysis, and optimization of application in order to prevent and reduce the incidence of intraventricular hemorrhages.