Antiphospholipid antibodies, genetic thrombophilia and fetal growth retardation

Aim: to study the role of antiphospholipid antibodies (AРA) and genetic thrombophilia as a potential cause of the development or a component in the pathogenesis of early and late fetal growth retardation (FGR).Materials and Methods. There was conducted a prospective randomized controlled trial with 118 women enrolled. The main group consisted of 83 patients, whose pregnancy was complicated by FGR degrees II and III, stratified into two groups: group 1 – 36 pregnant women with early FGR, group 2 – 47 pregnant women with late FGR. Women were subdivided into subgroups according to the FGR severity. The control group consisted of 35 pregnant women with a physiological course of pregnancy. АРА were determined according to the Sydney antiphospholipid syndrome criteria by enzyme immunoassay (ELISA): against cardiolipin, β2 -glycoprotein 1, annexin V, prothrombin, etc. (IgG/IgM isotypes); lupus anticoagulant – by the three-stage method with Russell's viper venom; antithrombin III and protein C levels – by chromogenic method; prothrombin gene polymorphisms G20210A and factor V Leiden – by polymerase chain reaction; homocysteine level – by ELISA.Results. AРA circulation (medium and high titers), genetic thrombophilic defects and/or hyperhomocysteinemia were detected in 40 (48.2 %) patients with FGR, which was significantly higher than that in the control group (p < 0.05): in group 1 (41.7 % of women) AРA (30.6 %) and AРA with genetic thrombophilia or hyperhomocysteinemia (11.1 %) were revealed; in group 2 (51.1 % of women) AРA (21.3 %), AРA with hyperhomocysteinemia (4.3 %), genetic thrombophilia (25.5 %), and due to hyperhomocysteinemia (2.1 %) were found. No differences in prevalence of thrombophilia rate in patients were observed related to FGR severity, but a correlation between the FGR severity and AРA titers was found.Conclusion. Testing for the presence of AРA, genetic thrombophilia and hyperhomocysteinemia should be recommended for patients with FGR (including those with FGR in medical history), especially in the case of its early onset. It is recommended to determine the full AРA spectrum.

Fetal growth retardation in multiple pregnancy: anthropometrical and haemodynamic criteria of early antenatal diagnosis

Ultrasound investigation o f feta l biometry and haemodynamic indices in fetoplacental system during pregnancy since 14 weeks was carried out in 53 women havingtwins as a result o f spontaneous pregnancy or using o f assisted reproductive technology methods. The frequency and possible reasons oflU G R development in multiple pregnancy were analyzed. To predict the possibility o f IUG R in II and III trimester o f multiple pregnancy the mathematic model was worked out based on the standard fetometric indices measuring at 14-16 weeks o f pregnancy.

MODERN DIAGNOSIS OF PLACENTAL DYSFUNCTION AND ITS COMPLICATIONS

The aim of the study was to improve the modern diagnosis of placental dysfunction and its complications. Materials and methods. The study involved a prospective survey of 70 pregnant women divided into the main group (pregnant women with placental dysfunction) (n = 50) and the control group (n = 20). The main group was divided into subgroups of pregnant women with placental dysfunction and fetal growth retardation (n = 30) and pregnant women with placental dysfunction without fetal growth retardation (n = 20). The control group comprised 20 pregnant women with physiological gestation. Apart from history taking, the study comprised obstetric and general clinical examination, evaluation of endothelium- dependent vasodilation, serum concentrations of soluble forms of vascular and platelet- endothelial molecules of cell adhesion 1, indicators of athrombogenicity of the vascular growth wall, uterine-placental-fetal blood circulation, pathomorphological and histometric examination of the placenta. Results. Based on the obtained clinical-morphological and endotheliotropic criteria, a personalized clinical algorithm for managing pregnant women with placental dysfunction was developed and implemented. Conclusions. Assessment of pregnancy results in a prospective clinical study showed that the proposed algorithm for personalization of the risk of perinatal abnormalities not only helped to avoid antenatal mortality, but also to prevent intranatal and early neonatal losses in patients with placental dysfunction and fetal growth retardation.

PECULIARITIES OF PREGNANCY COURSE, CHILDBIRTH, AND MORPHOFUNCTIONAL STATE OF PLACENTA IN WOMEN WITH INTRAUTERINE FETAL GROWTH RETARDATION

Fetal growth retardation is a severe obstetric pathology that is accompanied by significant reproductive losses and the cost of treating newborns. The aim of the study is to investigate the clinical difference between the course of pregnancy, childbirth, and morphofunctional state of the placenta in women who gave birth to children with low birth weight before gestational age and normal anthropometric parameters. Materials and methods. The study included 37 women; the individuals of the main group gave birth to a child with low birth weight before gestational age (n = 25), the comparison group consisted of women who had uneventful pregnancy and children born with normal anthropometric parameters (n = 12) . Results and discussion. Pregnancy and childbirth in the main group were registered mostly within the age range of 30 and 39, burdened with bad habits, accompanied by somatic and obstetric pathology. The predominant mode of preterm delivery in most of the main group was cesarean section caused by fetal distress in contrast to women in the comparison group. Analysis of the morphofunctional state of the placenta from the women in the main groups revealed both general structural-adaptive and structural-morphological changes that indicated compensatory hyperplasia of placental tissue in women with foetal intrauterine growth retardation that is characteristic of the compensated stage of chronic placental insufficiency. Conclusion. The multicomponent impact of various factors may contribute to an increased risk of fetal growth retardation and its progression, so timely correction of risk factors will help to improve the management of pregnancy and perinatal outcomes.

Prediction of perinatal outcomes in pregnant women with fetal growth retardation

Introduction. An important problem of modern obstetrics is the development and improvement of methods for predicting fetal growth retardation (FGR) and pregnancy outcomes in this pathology, since there are no proven effective treatments for FGR. Purpose of the study — to develop prediction criteria for newborn hypotrophy and cumulative adverse perinatal outcome in pregnant women with FGR. Objective. To identify key predictive factors for adverse perinatal outcomes in pregnancy complicated by FGR. Material and methods. A case-control, cohort-based study was conducted that included 155 pregnant women with FGR, who were divided into two groups after delivery: Group 1 included 90 patients with neonatal hypotrophy and Group 2 included 65 patients without neonatal hypotrophy. A comprehensive analysis of clinical and anamnestic, laboratory and instrumental data, peculiarities of the course of pregnancy and perinatal outcomes was performed. FGR was determined on the basis of ultrasound fetometry. Results. Factors associated with neonatal hypotrophy and unfavorable perinatal outcome were: impaired blood flow in the uterine arteries and/or umbilical artery, early preeclampsia and scarcity of water. Protective factors were antibacterial therapy for intrauterine infection, administration of low-molecular-weight heparin in the first trimester, and acetylsalicylic acid starting from the 12th to 16th weeks of gestation. Conclusion. The most promising measures in the prevention of FGR and adverse perinatal outcomes in this pathology may be timely prescription of antithrombotic correction and treatment of genital infections.

The rs5918 polymorphism in the ITGB3 gene increases the risk for preeclampsia in pregnant women with fetal growth retardation

Aim. To assess the relationship of rs5918 ITGB3, rs1126643 ITGA2 and rs5985 F13A1 polymorphic loci with the risk for preeclampsia (PE) in pregnant women with fetal growth retardation (FGR). Materials and methods. The study included 272 pregnant women, of which 76 had a combination of PE and FGR and 196 had FGR. In the studied groups, genetic testing was carried out for three polymorphic loci of candidate genes for hereditary thrombophilia (rs5918 ITGB3, rs1126643 ITGA2, and rs5985 F13A1). Results. The rs5918 genetic variant in the ITGB3 gene is associated with the development of PE in pregnant women with FGR: C allele of rs5918 ITGB3 increases the risk for this complication of pregnancy by 1,8 times (OR 1.761.77, p0.036, pperm0.038). The rs5918 polymorphism determines an increase in the affinity of DNA motifs for seven transcription factors (BDP1, ELF1, IRF, NRSF, Pax-5, Sp1, and Zfx), is a missense mutation and causes the Leu59Pro amino acid substitution in the 3 subunit of integrin, is multidirectionally associated with the expression of five genes (EFCAB13, TBKBP1, NPEPPS, MRPL45P2, THCAT158) and alternative splicing of two genes (EFCAB13, MRPL45P2), is located in the region of functionally important DNA regions (promoters and enhancers) in cell cultures and organs which are pathogenetically important for the formation of PE and FGR. Conclusion. The rs5918 polymorphism in the ITGB3 gene increases the risk for PE in pregnant women with FGR.

FEATURES OF THE CLINICAL COURSE OF PREGNANCY, CHILDBIRTH IN WOMEN WITH COVID-19 AT DIFFERENT PERIODS OF GESTATION

The study of the features of the clinical course of pregnancy, childbirth in women who have had COVID-19 at different periods of gestation is relevant, especially in the context of a modern pandemic. Purpose of work. To determine the features of the clinical course of pregnancy, childbirth in women with COVID-19 at different periods of gestation. Materials and methods. 57 women who were ill with Covid-19 at different stages of pregnancy were examined. Results and discussion. The peculiarities of the clinical course of pregnancy, childbirth in women who have undergone Covid-19 diseases in the 1st trimesterinclude the syndrome of threatened abortion (73.6 %), placental dysfunction (100%), fetal growth retardation syndrome (42.9 %); in the second trimester - syndrome of threatened premature birth (55.6 %), placental dysfunction (100 %), amniotic fluid pathology (63.2 %); in the third trimester - anemia - in 100 %, antenatal fetal distress - in 42.1 %, pareclampsia - in 47.4 %, pathological blood loss - in 26.3 %. Conclusions. The course of pregnancy and childbirth in women who have undergone COVID-19 diseases in different trimesters of gestation have certain clinical features. Gestational complications in women who were ill in the early stages of the first trimester include the syndrome of threatened abortion, spontaneous abortion, missed abortion, premature birth in the second trimester, fetal growth retardation syndrome in the second and third trimesters. The gestational complications in women who were ill in the second trimester include the syndrome of threatened abortion, premature birth, pathology of amniotic fluid (amniotic fluid of «black» color), the phenomenon of angiitis in the abdominal cavity, placental dysfunction, fetal growth retardation syndrome, distress fetus, antenatal fetal death. The gestational complications in women who were ill in the third trimester include the syndrome of threatened premature birth, placental dysfunction, and fetal distress.

Evaluation of Serial 2-D Sonographic Placental Volumetry and Umbilical Arterial Doppler and Their Correlation with Uterine Arterial Doppler in Predicting Adverse Fetomaternal Outcomes – An Observational Study from a Tertiary Care Centre in Pune, India

BACKGROUND An important part of human placental development is the extensive modification of maternal vasculature by trophoblasts. Fetal growth retardation (FGR) and preeclampsia (PE) are associated with deficient trophoblastic invasion and modification of the uterine spiral arteries leading to small-caliber vessels of high resistance which impairs placental blood flow, creating a hypoxic environment and subsequent oxidative stress. FGR and pre-eclampsia are important causes of maternal and perinatal morbidity and mortality and it is important to identify such ‘at risk’ pregnancies during routine antenatal care. Ultrasonography (USG) and colour-Doppler are readily available tools that may be used for identifying such ‘at risk’ pregnancies. The purpose of this study was to evaluate the accuracy of 2-D sonographic placental volumetry, umbilical arterial doppler and uterine arterial doppler in predicting adverse fetomaternal outcomes and compare the accuracy of these three tests with each other in terms of sensitivity and specificity. METHODS A total of 100 women were randomly selected from the antenatal clinics, and were subject to serial ultrasounds at 12 - 16 weeks, 20 - 24 weeks, and 28 - 32 weeks. The 2-D sonographic placental volume, umbilical and uterine arterial resistivity index (RI), and pulsatility index (PI) were measured. The pregnancies were followed up till delivery and the measurements were plotted against the actual placental weight and development of FGR and/or pre-eclampsia. RESULTS In pregnancies with FGR or pre-eclampsia, the placental volumes were low, and correspondingly the uterine and umbilical arterial RI and PI were high (increased impedance) as compared to the normal pregnancies. For the prediction of adverse outcomes, a receiver operating curve (ROC) analysis showed that placental volume and umbilical artery RI and PI had high sensitivity in the 1st-trimester, and high specificity in the 2nd-trimester. CONCLUSIONS 2-D sonographic placental volumetry and umbilical arterial Doppler studies may be used as 1st-trimester screening tools to predict adverse fetomaternal outcomes. These patients may be subjected to more intensive follow-up to minimize maternal and perinatal morbidity and mortality. KEYWORDS Doppler Ultrasonography; Fetal Growth Retardation; Placenta; Pre-eclampsia; Umbilical Arteries; Uterine Artery

Gene polymorphism of the xenobiotic biotransformation system and the intrauterine fetal growth retardation in female workers of industrial enterprises

Intrauterine growth retardation is recognized as one of the leading causes of incidence and mortality in infancy and early childhood in all the countries of the world. The causes and mechanisms of development of this process are decisive when choosing the tactics of nursing such children. Of particular importance is the understanding of the functioning of the mother-placenta-fetus system, in particular the mechanisms of suppression of the detoxification function of the placenta in connection with the polymorphisms of the genes of the I and II phases of the xenobiotic biotransformation system. The aim of the study was to determine the relationship between the polymorphism of the genes of the I and II phases of the xenobiotic biotransformation system with the intrauterine fetal growth retardation in women living in the South of the Kemerovo region and working under harmful labor conditions. A survey of 39 women of reproductive age living in the territory of Novokuznetsk was carried out, 20 of them worked at various enterprises of the city. The study group included 14 women who gave birth to children with intrauterine growth retardation of varying severity. The comparison group (control) consisted of 25 women. They did not have spontaneous miscarriages and they carried a child without the intrauterine growth retardation. The work investigated the frequency of occurrence of polymorphisms of genes of the xenobiotic biotransformation system - CYP1A2*1F, GSTM1 (they determine the activity of detoxification enzymes), as well as their combinations - in a group of working women and housewives who gave birth to children with intrauterine growth retardation. The forms of genes associated with the intrauterine fetal growth retardation, as well as genes associated with the resistance to this pathology, were identified. Combinations of gene forms of different phases of the xenobiotic biotransformation and their relationship with intrauterine fetal growth retardation were shown. There were no statistically reliable differences between various cohorts of women. A positive association of a high risk of the intrauterine fetal growth retardation in women with A/A CYP1A2*1F genotype and deletion polymorphism of the GSTM1 "-" gene has been shown. The heterozygous form of the C/A CYP1A2*1F gene polymorphism is statistically reliably associated with the resistance to this pathology, as well as the normally functioning GSTM1 "+" gene. Genotype A/A CYP1A2*1F in the combination with the deletion polymorphism of GSTM1 "-" gene is statistically reliably associated with intrauterine fetal growth retardation, and C/A CYP1A2*1F genotype in the combination with normally functioning GSTM1 "+" gene is associated with a low risk of the intrauterine fetal growth retardation. Comparative analysis of the relationship of the studied forms of genes of the xenobiotic biotransformation system with the intrauterine fetal growth retardation in the groups of female workers and housewives did not show statistically reliable differences.