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Shokirova Sadokatxon Muhammatsolievna, Assistant of chair of gynecology ASMI E-mail: [email protected]
EPIDEMIOLOGY, ETIOLOGY AND PATHOGENESIS OF INTRAUTERINE INFECTION
Abstract. In recent years, much attention is paid in the world literature placental growth factor (EDF), which are biologically active compounds that stimulate or inhibit the division and differentiation of various cells, including controlling the process c initial stages of placental development [1; 2; 4]. Keywords: placental growth factor, vascular endothelial growth factor.
In the development of the infectious process in the fetus, the type of pathogen, its virulence, ways of infection from mother to fetus, protective reserves of the mother's body and the ability of the fetus to immune response are important [11].
According to modern data [10; 12], the number of cases of IUI varies widely from 6 to 70%. Recently, the structure of infectious morbidity of pregnant women, parturient and puerperal, as well as the fetus and newborn has changed [5; 8]. It is proved that the causative agents of IUI are more than 27 types ofbacte-ria, many viruses, parasites, 6 types of fungi, 4 types of protozoa and rickettsia. Thus, according to a number of researchers [8; 12], chlamydia (17-50%) and viruses (herpes simplex virus, HSV - 7-47%, cytomegalovirus, CMV - 28-91.6%) are considered to be the predominant pathogens of antenatal infections., enteroviruses - 8-17%). Pathogens of intranatal infections are group B streptococcus (3-12%), staphylococcus (1-9%), fungi of the genus Candida (3-7%). Associations of pathogens occupy a leading position (75-95%).
It is known that most bacteria exist in nature in the form of specifically organized biofilms (biofilms) [2; 5; 7]. This form of existence creates a host of advantages for bacteria. Bacteria in biofilms have an increased survival rate in the presence of aggressive substances, immune protection factors and antibiotics [2]. In this regard, one of the main problems of practical medicine is the problem oftreating diseases of microbial origin.
In our study [5; 7], the results of bacteriological analysis of the species composition of the vaginal biotope revealed the strongest effect of Streptococcus faecalis (p = 0.00171), E. coli (p = 0.01424) and Staphylococcus epidermidis (p = =0.02714) for the implementation of intrauterine infection of the fetus. When evaluating pathogens detected in the cervical canal of pregnant women by the polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), the following was established: in the group without IUI, mycoplasma, chlamydia and urea plasma were 8%, CMV - 20%, HSV - 36%, Candida - 3%, associations - 60%. In the analysis of the group of newborns with the implementation of IUI, the most frequent pathogens were identified. So, mycoplasmas, chlamydia and HSV were found in 50%, CMV infection was detected in 45% of cases, urea plasmas (20%) and candida
(15%) were less common, associations were observed in 95%. The frequency of detection of pathogenic pathogens in newborns with signs of IUI was higher than in patients without infection.
In the pathogenesis of IUI, there are "maternal", "subsequent", "fruit" stages of development [2]:
The "maternal" stage reflects the beginning of the infectious process within the lower parts of the urogenital tract.
"Sequential" stage occurs with hematogenous spread of the inflammatory process, occurs when bacteremia and viremia.
At the "fruit" stage, the infection process spreads to the organs and tissues of the fetus. This occurs when the uteroplacental and placental-fruiting antimicrobial barrier is insolvent, the boundary of which is the layer of the chorale epithelium.
The main source of infection with IUI is the mother of the child, from which the pathogen enters the fetus (vertical transmission mechanism). In this case, infection occurs both in the ascending, trans placental and transovarial ways, and by contact and aspiration (directly during childbirth) ways. Moreover, for antenatal infections, hematogenous is the most typical, and for intrapartum infections, the ascending infection pathways [4; 10].
The impact of IUI on the embryo and fetus is the effect of a complex of the following factors [22]:
1. Pathological action of microorganisms and their toxins (infectious disease, fetal hypoxia, delayed development of the fetus).
2. Violation of the process of implantation and placenta-tion (low placentation, placenta previa).
3. Reduction of metabolic processes and immune protection of the fetus.
In the pathogenesis of the emergence and development of IUI, the duration of pregnancy is of particular importance [3; 6]. A fetus up to 14 weeks of pregnancy does not respond to infectious antigens, since it lacks immunocompetent cells, immunoglobulins and does not show immune reactions. With the onset of the second trimester of pregnancy, the mechanism of the impact of an ascending infection changes due to the fusion of decidua vera and decidua's capsular is into a single decidua's parietals complex. At this time, an ascending
infection can penetrate to the fetus from the vagina or cervical canal. From this period of pregnancy, the internal pharynx of the cervical canal comes into contact with the water membranes of the fetus and, in the presence of infection, microorganisms penetrate into the amniotic fluid. The antimicrobial properties of the amniotic fluid acquire only after the 20th week of pregnancy, when an inflammatory proliferative reaction develops in response to the effect of an infectious agent, limiting further infection penetration, due to the appearance of lysozyme, complement, interferons, immunoglobulins [1; 7]. In the third trimester of pregnancy, antibacterial protection of amniotic fluid increases. During this period, the role of the exudative component prevails in the inflammatory reaction of the fetal tissues, when inflammatory leukocyte reactions develop in the fetus (encephalitis, hepatitis, pneumonia, interstitial nephritis) in response to infection penetration [6].
Especially dangerous when IUI in the II and III trimesters of pregnancy is damage to the fetal brain, which can lead to mental retardation, delayed psychomotor development of children [3; 7]. Intrauterine infection by the pathogens of the CNS structures in the fetus is accompanied by various severe abnormalities in the formation of the brain (hydrocephalus, sub ependymal cysts, cystic degeneration of the brain substance, abnormalities of the cortex, microcephaly). It is also possible the development of ventriculitis (deformity of the choroid plexus, heterogeneity or doubling of reflection from ependymal of the ventricles) [11].
Thus, infection of the fetus in the later stages of pregnancy does not, as a rule, lead to the formation of gross malformations, but can disrupt the functional mechanisms of cell and tissue differentiation [10; 11].
Changes in the state of the fetus and the functioning of the fetoplacental system, caused by intrauterine infection of the fetus, affect the composition and properties of the amniotic fluid [1; 9; 26; 30]. When injected into the amniotic fluid of an infectious agent, its unhindered reproduction occurs with the subsequent development of chorioamnionitis [1; 9]. The fetus finds itself in an infected environment, which creates favorable conditions for the infection of the fetus by contact, i.e. through the skin, mucous membranes, respiratory and gastrointestinal tracts.
The syndrome of "amniotic fluid infection" develops, the mechanism of its occurrence is as follows [2]:
1. Upon ingestion and aspiration of infected water in a newborn, signs of intrauterine infection appear (pneumonia, enter colitis, vesicles, omphalitis, conjunctivitis, etc.).
2. At the same time, microorganisms, spreading through the membranes or between them, reach the basal plate of the placenta (deciduitis). The further spread of the inflammatory reaction leads to the development of choronitis (placentitis),
manifested by leukocyte infiltration of intravillus space and endovascular ties in the chorial plate. Vasculitis in the decidua membrane, stem and terminal villi lead to vascular obliteration, the appearance of heart attacks, calcifications, massive fibrinous deposits, which may manifest as "premature maturation of the placenta."
3. Polyvascular infection during intrauterine infection is usually secondary and is a manifestation of kidney or urinary tract infections of the fetus. The reason for its development is the change in the ratio of the processes of production and resorption of amniotic fluid by the cells of the amniotic epithelium against the background of amnionitis.
4. In the genesis of the symptom complex of placental insufficiency with IUI, the main role belongs to vascular disorders.
5. A typical manifestation of intrauterine infection are miscarriage and premature birth [24]. Premature development of labor and untimely rupture of the fetal membranes are caused by the action of bacterial phospholipases that trigger the prostaglandin cascade and the damaging effect of inflammatory toxins on the fetal membranes.
6. Due to the fact that the phospholipases of gram-negative bacteria contribute to the destruction of surfactant in the lungs of the fetus, the newborn develop respiratory disorders.
In the modern literature [4; 9] there are many works devoted to the study of the relationship of immunological parameters and the severity of the infectious-inflammatory process during pregnancy. Increasingly, in the foreign and domestic literature, data appear on the relationship of bacterial invasion and cytokine synthesis by the cells of the amnion, chorion, decidual and fetal tissues [5]. The reproduction of microorganisms in the amniotic fluid leads to an increase in the level of lipopolysaccharides, which activate the synthesis of cytokines by fetal trophoblast cells. The study of changes in the cytokine system, which provides the processes of intercellular cooperation, growth and differentiation of lymphoid cells, hemopoiesis and neuroimmune-endocrine interactions, seems promising for IUI. In the pre-implantation period and during the development of pregnancy, cytokines are actively produced by a multitude of maternal and fetal cells, in particular, by deciduae cells of the uterus and trophoblast cells. It has been established that cell cultures have unequal ability to synthesize cytokines under the influence of lipopolysaccharides. Thus, tumor necrosis factor (TNF) is produced by amnion cells, interleukins (IL) -6 and IL-8 are produced by amnion and chorion, and IL-1 is produced only by chorion [9]. According to N. V Ordzhonikidze [14],from a variety of pro-inflammatory (IL-1, IL-2, IL-6, IL-8, IL-15, TNF, etc.) and anti-inflammatory (IL-4, IL-10, IL-13, transforming growth factor and others. Cytokines are considered to be the
main markers of the inflammatory process in human tissues and organs: IL-1, IL-6, IL-10, TNF [9].
Modern methods of diagnosis of intrauterine infections
The prevalence of IUI among the causes of adverse outcomes, the high level of infection in pregnant women and puerperas necessitate the search for reliable methods for its diagnosis. The no specificity of the clinical manifestations of IUI creates diagnostic difficulties, which dictates the need for the combined use of clinical and laboratory research methods. In the last decade, bacteriological and immunological methods have been the main diagnostic methods for IUI [10; 11].
There are 3 stages in the diagnosis of intrauterine infection: 1) diagnosis during pregnancy; 2) early diagnosis at the time of childbirth; 3) diagnosis in the development of clinical signs of infection in the early neonatal period [11].
Of the non-invasive methods of prenatal diagnosis of IUI, the most informative are ultrasound and Doppler sonography [6; 7]. Direct methods of laboratory diagnostics (cordocen-tesis, dark-field microscopy, PCR, ELISA, culture) can detect the pathogen in biological fluids or tissue biopsies of an infected child. Indirect methods of diagnosis of IUI include the clinical symptoms of the mother, ultrasound and help only to make a presumptive diagnosis of IUI [10]. Screening tests of IUI in newborns include examinations of smears of amniotic fluid, placenta, umbilical cord blood culture and contents of the stomach of a newborn, sometimes blood culture [6; 7; 10]. The "gold standard" of post-diagnosis of IUI is a histological examination of the placenta, umbilical cord and fetal membranes [4; 10].
Any changes in homeostasis in the mother's body are reflected in the cellular and chemical indicators of the amniotic fluid, which very subtly characterize the course of the pathological process, and therefore the amniotic fluid can serve as an important diagnostic material [1; 6]. According to I. V. Bakhareva [1], the most significant in the diagnosis of IUI is the determination of the antimicrobial activity of amniotic fluid, based on the migration of leukocytes in it when bacteria accumulate in the amniotic membrane, exceeding 103 CFU / ml. The appearance in the amniotic fluid of a large number of leukocytes, an increase in cytosis due to epithelial cells without the detection of microflora may indicate IUI.
Currently, great importance is attached to ultrasound research methods, which can be used to determine indirect signs
of fetal IUI (polyhydramnios, ventriculomegaly, microcephaly, hepatomegaly, an increase in the thickness of the placenta, fine suspension in the amniotic fluid) and structural changes in various organs [4; 11].
We have developed the necessary list of diagnostic measures for the early detection of IUI [19].
The complex survey of pregnant women included:
1. General clinical and biochemical blood and urine tests with the definition of standard indicators.
2. Determination of TORCH-complex pathogens using PCR in vaginal smears, amniotic fluid.
3. Determination of antibodies in the blood to chlamydia, mycoplasmas and ureaplasmas, CMV and HSV by ELISA.
4. Conducting amine test, pH-metry vaginal contents.
5. Bacterioscopic examination of the contents of the vagina, cervical canal and urethra.
6. Bacteriological examination of the maternal surface of the placenta, amniotic fluid, intestinal contents.
7. Determination of the level of pro-inflammatory (IL-1^, TNF) and anti-inflammatory (IL-10) cytokine in the amniotic fluid, maternal venous serum and fetal umbilical cord blood.
8. Ultrasound scan of the fetus, amniotic fluid and placenta.
9. Histomorphological study of the placenta.
The complex examination of newborns included:
1. Apgar score, measurement of body weight and length at birth, dynamics of increase in body weight before discharge from the maternity hospital.
2. Determination of antibodies in the blood to chlamydia, mycoplasmas and ureaplasmas, CMV and HSV by ELISA.
3. Bacteriological examination of scrapings from the conjunctiva, posterior pharyngeal wall and vulva.
4. Identification of clinical signs of IUI together with a neonatologist.
A comprehensive study of the species composition of microorganisms of the birth canal, amniotic fluid, placenta, newborn, determination of antigens and antibodies to the suspected causative agent in cord blood and amniotic fluid, histological examination of the afterbirth can determine the pathway of infection of the child, the nature of the pathogen and clarify the amount of additional diagnostic studies in IUI also identify therapeutic and preventive measures in the early neonatal period.
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