Резюме
Пасієшвілі Н.М. Оптимізація підходів до лікування внутрішньоутробного інфікування плоду.
В роботі представлені результати обстеження 60 вагітних з материнсько-плодовою інфекцією та внутрішньоутробним інфікуванням плоду. Використання сучасних методів дозволило вивчити можливості використання медичного озону в лікуванні внутрішньоутробних інфекцій, розробити патогенетичні підходи к тарапії вказаної патології, методи профілактики.
Ключові слова: внутрішньоутробне інфікування плоду, озонотерапія.
Резюме
Пасиешвили Н.М. Оптимизация подходов к лечению внутриутробной инфекции плода.
В статье представлены результаты обследования 60 беременных с материнско-плодовой инфекцией и внутриутробным инфицированием плода. Применение современных методов позволило изучить возможности использования медицинского озона в лечении внутриутробных инфекций, разработать патогенетические подходы к терапии указанной патологии, способы профилактики.
Ключевые слова: внутриутробное инфицирование плода, озонотерапия.
Summary
Pasieshvili N.M. Ways to optimize the treatment of intrauterine fetal infection.
The article presents results of the examination of 60 pregnant women with maternal-fetal infection and intrauterine infection of the fetus. Application of new techniques allowed us to study the possibility of using medical ozone in the treatment of intrauterine infection, to develop pathogenic approaches to the treatment of this pathology, and the methods of its prevention.
Key words: intrauterine infection of the fetus, ozone therapy.

УДК 615.38.015.2:618.3-06:616.9-022-053.1

Харьковский областной клинический перинатальный центр

61052, г. Харьков, ул. Маршала Малиновского, 4

Kharkiv Regional Clinical Perinatal Centre

61052, Kharkov, str. Marshal Malinovsky, 4

pasonana@mail.ru

Introduction. According to the literature, intrauterine infections (IUI) represent a group of infectious and inflammatory diseases of the fetus and young children which are caused by various pathogens, but are characterized by similar epidemiological characteristics and not infrequently have similar symptoms. Congenital infections develop as a result of intrauterine (ante- or intrapartum) infection of the fetus, in most cases the source of infection of the fetus being the mother [3,8]. However, the use of invasive methods of monitoring women during gestation (amniocentesis, cordocentesis) may lead to iatrogenic infection of the fetus. [4]. The true incidence of congenital infection has not yet been established, but, according to some authors, the prevalence of this disease reaches 10-35% [1,5]. IUI are severe diseases and largely determine the level of infant mortality.

In this case, the relevance of IUI is not only due to significant peri- and postnatal losses, but also due to the fact that the children who had severe forms of congenital infection, very often develop serious health problems that not infrequently lead to disability and reduced quality of life as a whole. [6]. Considering the widespread and gravity of the prognosis, it can be concluded that the development of methods for the effective treatment and efficient prevention of congenital infection is one of the priorities of modern perinatology. At present, the focus is on early screening of the pregnant for the presence of ТОRСН infections, the use of microbiological and ultrasound diagnostics in order to detect markers of IUI, the presence of placental dysfunction, and fetal specification [7].

However, there is evidence of abuse of immunological homeostasis in the IUI fetus, which is, unfortunately, contradictory or not well studied.

Currently, IUI treatment is mainly aimed at the treatment of infections in the mother, at the very outside – treatment of infectious and inflammatory diseases of the newborn, which is not always effective. The use of antibiotics has a number of side effects for both mother and fetus, and does not always produce the desired result. Recently, the practice of medicine has found widespread use of ozone, due to its high efficiency and lack of side effects [2]. Consequently, the development of new treatments for this disease, investigation of the possibility of using ozone therapy, determining its impact on the status of the mother and the fetus, the confirmation of its clinical effectiveness – are the pressing issues of modern obstetrics, and that led to the choice of the theme of this study.

The aim of the work was to increase the effectiveness of treatment by determining IUI pathogenetic changes in the pregnant and the development of new approaches to the treatment with the use of medical ozone.

Materials and methods. To achieve this goal, we examined 80 pregnant women (pregnancy – weeks 28-36), who were divided into clinical groups according to therapeutic approaches.

Group I (control) consisted of 20 women with physiological pregnancy. Group II included 20 women with a maternal-fetal infection (MFI), who received conventional antibiotic therapy stipulated by MH of Ukraine Decrees and Cinical protocols. [7]. Group III included 20 women with MFI, who received medical ozone. Group IV included 20 pregnant women with MFI who received combination therapy, which included the traditional treatment combined with ozone therapy. Ozone therapy represented intravenous injection of 200 ml of ozonated saline solution on alternate days; the course of treatment – 5 infusions. All pregnant women underwent a complete clinical and laboratory examination, bacteriological examination of the contents of the vagina, screening for TORCH-infection by ELISA and PCR. To determine the status of the fetus, its biophysical profile was estimated; Doppler flow indices in the "mother-placenta-fetus", the data of cardiotocographic study were also estimated. Ultrasound examination was carried out on Aloka 1100 "Flexus" using transabdominal 3.5 MHz convex probe in accordance with the screening program by the standard technique. All women were tested for placental proteins in the peripheral blood, since it is known that they describe the state of the fetoplacental complex: placental α1-microglobulin (PP12), α2-microglobulin of fertility (PP14), trophic β-glycoprotein (SP1) and testosterone-estradiol binding globulin (SSBG).

To study the immune status, we investigated the basic cellular and humoral immunity indicators (T and B lymphocytes, subpopulation of T-helper and T-suppressor cells), calculated immunoregulatory index (IRI), CD4 + / CD8 +, determined the level of serum of immunoglobulins (A, M, G ), the content of cytokines in the peripheral blood – tumor necrosis factor-a (TNFa), interleukin (IL-1, IL-2, IL-6), the level of the circulating immune complexes (CIC). We determined the composition of CEC including the release of multimolecular (> 19S), medium-molecular (11S-19S) and small-molecule (<11S) complexes by using Digeon et al. method of precipitation modified by V.M. Frolov et al, 1986.

Statistical analysis of the results of research was conducted by Student's t-test.

Results and discussion. The comparison of the clinical characteristics revealed that IUI are more likely found in women who have history of inflammatory diseases of the female reproductive organs (68.9%), artificial (26.1%) and spontaneous abortions (52.2%), preterm delivery (16.7%), and missed abortion (8.4%).

The study showed that the main group showed various degrees of changes in rates of specific cellular immunity, which were characterized by an imbalance of the subpopulation of T lymphocytes. At the same time, the pregnant showed changes in total population of T lymphocytes (CD3 +), ie reducing their total number to 49,2 ± 5,6%, which was significant in the pregnant with MFI, in contrast to the patients with normal pregnancy (p <0.05). The pregnant with MFI also developed immunological dysfunction, manifested deficiency of circulating T-helper cells (CD4 +), reaching the level of 34,5 ± 3,2%, with a slight decrease in T-suppressor cells (CD8 +) and changes in the immunoregulatory index CD4 + / CD8 + (62, 5 ± 7,3%). The content of B-lymphocytes (CD22 +) in the pregnant with MFI decreased, its multiplicity with respect to the control was 1.3 times. Cytokine profile was characterized by increased IL-1 (62.5 ± 4.7pg/ml), IL-2 (6.1 ± 0.7pg/ml) and TNF (59.2 ± 3.9pg/ml), which indicates increased production of proinflammatory cytokines in the MFI. At the same time, there was an increase by 2.4 times of the CIC level, mainly due to the most pathogenic medium- and low-molecular complexes (11S-19S) and disimmunoglobulinemia with a tendency to reduce the level of IgM and IgG; those violations were correlated with the severity of the MFI. Accumulation of immune complexes in the blood led to activation of immune reactions, and their deposition in the walls of the microvasculature interferred with the hemoperfusion, leading to tissue hypoxia and increased, in turn, lipid peroxidation and metabolic intoxication.

Pathogenic CIC which are fixed on the surface of cell membranes, including the placenta, close circulus vitiosus of immune responses, most likely determining further damage of the placenta. Therefore, the pregnant with MFI formed secondary immunodeficiency, mainly on the relative suppressor variant, moderate activation of immune reactions, and disimmunoglobulinemia, which had a strong tendency to reduce the level of IgM while increasing the rate of the CIC, indicating increased autoimmune component. Severity of immunological disorders correlated with the severity of symptoms of secondary immunodeficiency. Efficient use of medical ozone in treatment of MFI in pregnancy was monitored by clinical and immunological parameters.

Introduction of ozonated saline solution had a marked immunocorrective impact, normalized humoral immunity (IgA, IgM and IgG), enhanced the effect of T-suppressor cell-mediated immunity, reduced the level of proinflammatory cytokines (IL-1, IL-2, TNF) and content with medium weight complexes. The use of medical ozone alone or in the combined therapy has been an effective treatment IUI aimed at normalization of immunological changes in the blood of the pregnant, improving the utero-placental blood flow, increase of protein-synthesizing function of the placenta, reducing the signs of maternal-fetal infection, and improvement of the condition of a newborn.

The use of ozone therapy has led to an increase in the basic fetometrical parameters (biparietal diameter, abdominal circumference, femur length), significantly reduced the number of destructive changes in the placenta: echodensity of the placenta decreased by 1.9 times, the thickness – 1.5 times, sound conductivity – 1.7 times, intervillous space expansion – 2.2 times, which indicates the high efficiency of the proposed therapy.

Under the influence of medical ozone occurs normalization of protein-synthesizing function of the placenta (increase of SP1 by 2.1 times, PP14 – by 2.7 times; decrease of PP12 – by 2.2 times), which will result in the proper development and functioning of fetoplacental complex.

Also, according to CTG, significantly improved the condition of the fetus; there occurred complete normalization in the pregnant with mild impairment, as well as in 90% of the pregnant with MFI (moderate impairment), as opposed to traditional treatment, which was effective in only 46.3% with mild impairment and 16.7% with the moderate impairment.

Also, the use of medical ozone significantly improved the fetal biophysical profile, especially in cases of marked intrauterine infection of the fetus. Doppler echocardiography indicators in the pregnant with MFI showed violations of the utero-placental blood flow (increased vascular resistance in the umbilical artery and uterine arteries). As a result of the treatment with the use of medical ozone, 75% showed normalization of blood flow in the fetoplacental system, while the traditional treatment – only 15% of pregnant women.

Analyzing the clinical groups, we determined a significant decrease in number of gestational complications, especially when using ozone therapy. In particular, a reduction in the frequency of preterm birth, placental insufficiency, signs of maternal-fetal infection, symptoms of intrauterine fetal infection, infection in the newborn. In the pregnant with MFI, the smallest number of preterm birth was observed in the group where the pregnant women received combined treatment. The highest percentage of complications in childbirth was determined in the second clinical group. Attention is drawn to the fact that every second pregnant woman had untimely rupture of membranes. Under the influence of the therapy, has improved the indicators of the health of newborn children immediately after birth, reduced the number of infected infants. These positive effects have been achieved probably due to ongoing correction with the use of ozone therapy.

Conclusions:

1. The use of medical ozone alone or in the complex therapy is an effective treatment of MFI aimed at normalization of immunological changes in the blood of the pregnant, improving of utero-placental blood flow, increase protein-synthesizing function of the placenta, reducing the incidence of infectious and inflammatory diseases of the newborn.

2. The use of ozone therapy reduces the development of placental dysfunction, fetal distress, and improves pregnancy outcomes: increases the number of normal births, prevents untimely rupture of membranes, thereby reducing the delivery of an immature and premature fetus; thus, the use of ozone therapy can be recommended for use in the treatment of intrauterine infection of the fetus.

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