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Секция 7. Медицина
частичной посторонней помощи — 16,1%; с полной зависимостью от посторонней помощи — 27,5%; летальность составила 6,7%.
Обсуждение результатов
Рост заболеваемости объясняется значительным увеличением распространенности среди населения Сургута большинства основных факторов риска ИИ. Возрастает количество повторных инсультов и инсультов у лиц, перенесших инфаркт миокарда. Заболеваемость и смертность в Сургуте значительно выше, чем в Урала и южных районах Западной Сибири
[5; 6]. Выявленная метеозависимость развития ИИ отражает окологодичные колебания заболеваемости, но не является причиной ее повышения.
Относительно благоприятные исходы и низкая стационарная летальность объясняются несколькими факторами: госпитализацией всех больных ИИ, а также пациентов с ТИА и церебральными гипертоническими кризами; незначительным количеством больных пожилого и старческого возраста, составляющих всего 9-12% всех госпитализированных с ИИ, а также низким процентом атеротромботических ИИ.
Список литературы:
1. Айриян Н. Ю. Анализ данных эпидемиологического мониторинга инсульта в Российской Федерации: Ав-тореф. ... дис. канд. мед. наук. М., 2006.
2. Богданов А. Н. Ишемический инсульт в городском центре Среднего Приобья: Автореф. дис. ... канд. мед. наук. Пермь, 1990. - 18 с.
3. Быкова О. Н., Гузева О. В. Факторы риска и профилактика ишемического инсульта//Вестник Российской военно-медицинской академии, 2013. - № 4. - С. 46-48.
4. Гусев Е. И., Мартынов М. Ю., Камчатнов П. Р. Ишемический инсульт. Современное состояние пробле-мы//Доктор. Ру, 2013. - № 5. - С. 2-7.
5. Коваленко А. В., Гилева О. А. Эпидемиология и факторы риска инсульта в Кемерове. Бюллетень сибирской медицины. 2008. 5. 170-175.
6. Фейгин B.JI. Эпидемиология мозгового инсульта в условиях крупного города Западной Сибири по данным регистра: Автореф. дис. ... канд. мед. наук. - Новосибирск, 1984. - 20 с.
7. Barata A. D., Ho S. Y., Brass L. M. Long-term mortality in cerebrovascular disease//Stroke, 2003. - 34. - P. 669-704.
8. Lopez A. D., Mathers C. D., Ezzati. Global and regional burden of disease and risk factors: Sistematic analysis of population health data//Lancet, 2006. - № 367. - Р. 1747-58.
Hodjamova Nargiza Karimovna, assistant of the Department of Neonatology Tashkent Pediatric Medical Institute,
Tashkent, Uzbekistan Rakhmankulova Zukhra Jandarovna MD, professor of the Department of Neonatology Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan
Kamalov Zaynitdin Sayfutdinovich, MD, head of Laboratory Institute of Immunology of Academy of Sciences of the Republic of Uzbekistan, Tashkent, Uzbekistan E-mail: [email protected]
The cytokine status in infants with intrauterine growth retardation born with asphyxia
Abstract: Immunological examination of 89 mothers and 89 children was held. 38 of them are newborns with infants with intrauterine growth retardation (IUGR) born with asphyxia (basic group), 32 newborns — with IUGR born without asphyxia (group of comparison), and 19 are healthy newborn children (control group). In newborns with IUGR born with asphyxia there is a significant imbalance of pro-inflammatory and anti-inflammatory cytokines in peripheral blood serum.
Keywords: intrauterine growth retardation, asphyxia, clinical signs, cytokines.
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Intrauterine growth retardation (IUGR) of the fetus is one of the most frequent complications of pregnancy, which leads to adverse perinatal outcomes. The frequency of IUGR varies within the limits of 4.539%, and in structure of perinatal morbidity has a leading position. Infant mortality in this group is 8-10 times higher than among newborns with normal physical development [1; 2].
Adverse pregnancy negatively affects the development of the fetus, causes rapid exhaustion and inadequate reactions of adaptation in the neonatal period. The severity of newborns with IUGR in the first week of life mainly caused by intrauterine hypoxia and intrapartum asphyxia, which contribute to a variety of neurological disorders and instability of metabolic processes [3; 4].
However, IUGR as a result ofplacental insufficiency in extragenital and infectious diseases in mothers, on the one hand, is a factor contributing to the manifestation of specific perinatal infections and adversely affects their course in children, on the other hand, is often one of the clinical signs of congenital infections. The available scarce and ambiguous information about the state of the immune system in newborns undergoing severe asphyxia indicate modified immunological reactivity of this category of newborns. Most researchers came to the conclusion that chronic intrauterine hypoxia and severe asphyxia cause early inclusion of the immune system with possible further violation of its functions with the development of the secondary immune deficiency, which causes a predisposition to the development of infectious complications in these children. The changes of immunological indices associated with impaired regulation of immunogenesis, and with the direct influence of hypoxia on the state of the immune system [5-8].
The aim of the research was to study the concentration of proinflammatory and anti-inflammatory cytokines in newborns with IUGR born with asphyxia, in relationship with the characteristics of the course of the late neonatal period.
Materials and methods. During the work we examined 191 newborn children, including 172 newborns with IUGR and 19 healthy children. All the children were divided into 3 groups: I basic group — 79 newborns with IUGR born with asphyxia, II — group of comparison — 93 newborns with IUGR born without signs of asphyxia, III-control group — 19 healthy newborn children without congenital anomalies and hereditary diseases.
The concentration of interleukin and interferon (IL-1b, IFN-y, IL-4) in serum was determined by the method of solid-phase enzyme immunoassay using the test systems of «Cytokines» LTD (St. Petersburg, Russia). When analyzing historical data, taken from the histories of the newborns, the courses of pregnancy and delivery, the presence of risk factors in antenatal and intranatal periods were studied.
All newborn of basic group were born in severe and moderate asphyxia from mothers with adversely flowed pregnancy. Gestational age of infants of core group was 27-41 weeks, and in the group of comparison — 3740 weeks.
Results and discussion. Analysis of chronic somatic pathology among mothers has shown that 25.9% of women of the basic group suffered from diseases of the respiratory system, and women in the group of comparison — 12.5%; from diseases of gastrointestinal tract, 14.8% and 10.4% accordingly. Diseases of the cardiovascular system in mothers of the group I met in 18.5%, and in the group of comparison — in 6.3% of cases. Diseases of urinogenital sphere in the basic group were 13.0% of mothers in the group of comparison at 10.4%. Among antenatal risk factors leading role in children of the core group had developed fetoplacental insufficiency and chronic fetal hypoxia, which accounted for 81.5%, in the group of comparison, these indicators amounted to 64.6%. Acute respiratory virus infection during pregnancy in women of basic group were noted in 51.9% cases, and in the group of comparison — in 45.8%.
Pathological delivery in the 1st group amounted to 40.7%, in the 2nd — 25%. Early rupture of the amniotic fluid in a core group met in 51.9%, and in the group of comparison in 29.20%, premature detachment of the placenta, respectively 9% and 2% of cases.
Important to assess the clinical status of newborn children of IUGR born with asphyxia and identify the nature of various complications is the analysis of pathological conditions arising studied children in the neonatal period. Intrauterine pneumonia in children of the basic group appeared in 39.2±6.6%, in the group of comparison — in 15.1±5.2%, which was significantly less (P<0.01). Septic process in children of the basic group developed in 22.8±5.7%, in the group of comparison — in 9.7±4.3% (P<0.01). In our research children of the basic group are significantly more likely to have developed complications such as haemorrhagic syndrome (11.4±4.3% against 5.4±3.3%), bowel paresis (7.6±3.6% against 4.3±2.9%), which was 2.1 times and 1.8 times more than in the children in the group of comparison.
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We conducted a study to determine the level of production of IL-1b as important mediator, which is one of the most universal regulators of immune and inflammatory responses with a wide range of biological effects, including proliferation of T- and B-lymphocytes, antibody production, induction of synthesis of other cytokines (table 1). When studying the concentration of IL-1b in the control group (peripheral blood) level ranged 128.0-280.0 PG/ml and in the average totaled 200.4±9.74 PG/ml. Synthesis of IL-1b in serum of umbilical cord blood of newborns from healthy mothers was significantly reduced and amounted to 117.4±4.51 PG/ml (P<0.05).
The concentration of this monokin in serum of umbilical cord blood in newborns with IUGR born in asphyxia differed significantly from the control values in the peripheral blood of healthy newborns and amounted 162.3±3.52 PG/ml. This indicator in umbilical cord blood was 1.4 times higher than that in children born from healthy mothers (P<0.05). The obtained results allow us to think about the dependence of the level of production of IL-1b on the nature of the pathological process, as evidenced by raising it in newborns with IUGR
born with asphyxia.
Interferons play an important role in coordinating the functions of multi-component immune system. These are a group of biologically active proteins or glycoproteins, synthesized by the cell in the process of protective response to foreign antigens. One of them — IFN-y — is generated due to stimulation of T-lymphocytes and the EC and produced only by immunocompetent cells. It also plays an important role in the development of the immune response by Th1-type, contributing to the expression of beta-2 subunit of receptors to IL-12. In addition, IFN-y blocks the development of Th2 dysbalance-type, inhibiting the synthesis of IL-4 and prolif-eratiou cells Th2 dysbalance-phenotype. It doesn’t have antiproliferative actions on Th1 cells, since they do not express a beta-2 receptor subunit of IFN-y.
Interferon system is aimed at the recognition and elimination of alien genetic information. The most important function of IFN-y is its involvement in the implementation of the linkages between lymphocytes and macrophages, and in the regulation of cellular and humoral immune responses.
Table 1. - Concentrations of cytokines in serum of peripheral and umbilical cord blood of newborns.
Cytokines Peripheral blood Umbilical cord blood
Control group n-19 Basic group n-38 Group of comparison n-32 Control group n-26 Basic group n-38
IL-1b 200.4±9.74 512.5±8.31* 417.4±4.08* 117.4±4.51 162.3±3.52*
IFN-y 25.7±1.65 15.4±0.86* 12.3±0.61* 24.3±1.39 28.1 ±1.35*
Note: Р — significant differences in compare to control group (P<0.05).
The results of our research showed that in healthy newborns in peripheral blood serum concentration of IFN-y averaged 25.7±1.65 PG/ml, in umbilical cord blood remained the same (24.3±1.39PG/ml). In umbilical cord blood of children with IUGR born in asphyxia, the level of IFN-y was increased to 28.1±1.35 PG/ml, which significantly differed from those of other groups.
The concentration of IFN-y in newborns with IUGR born without asphyxia reduced to 12.3±0.61 ng/ml, which was significantly lower than in the control group (P<0.05). In newborn infants with IUGR born with asphyxia concentration of IFN-y, remaining significantly low (15.4±0.86 PG/ml) against reference values tend to increase, but it does not differ from parameters of children with IUGR born without asphyxia.
Thus, in newborns with IUGR born with asphyxia there is a 1.4 times increase of IL-1b in cord blood compared with umbilical cord blood in healthy newborns, and the tendency to the increase of IFN-y.
In the peripheral blood of infants with IUGR born with asphyxia observed 2,6 times increase in the concentration of IL-1b, compared with peripheral blood in healthy newborns, and 1.7 times reduced levels of IFN-y. The imbalance of cytokines may be one of the causes of aggravation of the pathological process in IUGR.
Currently some of the main reasons for the development of immunodeficiency become clear. One reason is the violation in the organism under the influence of various factors, including birth asphyxia, immunoregulatory processes carried out with the help of a Th1 — and Th2 — helpers. As known, the first synthesize cytokines that stimulate cellular immunity (IL-1, 2, 6, 8, 12, IFN, TNF and other), the second synthesize cytokines that stimulate humoral immunity (IL-4, 5, 10, TGF-b and others). In a normally functioning body there is a certain balance of interaction between Th1-and Th2-helpers. But a strong change of their activity under the influence of any effect, can lead to
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serious adverse effects in the functioning of the immune system in general. It is established that hypoxia may cause activation of Th2-helpers and synthesis of cytokines that provide suppressive effect on cellular immunity.
The activation of specific immune response is mediated by a number of cytokines (IL-2, IL-4 and others), regulating the growth and differentiation of lymphocytes and contributing to this phase ofthe immune response. One of them — IL-4 — has a wide spectrum of biological action. This lymphokine (molecular weight 15-20 kDa) is produced by T cells (Th2) and is a factor of differentiation for T — and B-lymphocytes. The strongest effect of IL-4 provides for the regulation of formation other cytokines through participation in numerous biological processes, such as the immune response and the inflammatory response. IL-4 limits the synthesis of macrophage inflammatory IL-1b, 6, 8, 12, TNF-a, formation of highly active metabolites oxygen, nitrogen. In addition, IL-4 plays as a cofactor of proliferation of dormant B-lymphocytes and induces synthesis of IgE and IgG in these cells. Known ability of IL-4 to generate activity of lymphokine-activated cells (LAC) and to strengthen anti-tumor activity of the macrophages.
In healthy newborns level of cytokine IL-4 in cord blood was 26.5±1.57 PG/ml, which was significantly lower than in newborns with IUGR born with asphyxia (P<0.05). In peripheral blood its increasing was observed, and the content of the latter averaged 52.2±2.31 PG/ml, with fluctuations 32-73 PG/ml (table 2).
In newborns with IUGR born without asphyxia the decrease of the level of IL-4 to 22.4±1.07 PG/ml in the peripheral blood was observed, which was significantly lower than in the control (P<0.05). In newborns with IUGR born with asphyxia concentration of IL-4 recoreing significantly low (26.7±1.69 PG/ml) with regard to the control values in the peripheral blood, tends to increase, but it significantly differs from the indicators of children with IUGR born without asphyxia.
The level of IL-4 in cord blood of newborns with IUGR born with asphyxia was not different from the level of those in the peripheral blood serum of healthy newborn babies. The concentration of this cytokine in the peripheral blood of infants born with IUGR born without asphyxia 1.2 times lower than in newborns with IUGR born with asphyxia.
Table 2. - Concentrations of IL-4 in serum of peripheral and umbilical cord blood of newborns.
Cytokines Peripheral blood Umbilical cord blood
Control group n-19 Basic group n-38 Group of comparison n-32 Control group n-26 Basic group n-38
IL-4 60,8±4,53 26,7±1,69 22,4±1,07 26,5±1,57 52,2±2,31
P P<0,05 P<0,05 P<0,05
Thus, in the early postnatal period of immune adaptation of healthy full-term newborns on the background of high antigenic load noted the development of laboratory signs of systemic inflammatory reaction, resulting in a significant increase of proinflammatory cytokines concentrations in serum. The identified laboratory signs in physiological conditions are not accompanied by the development of the clinical picture ofsystemic inflammation, infectious toxicosis and multiorgan failure. Apparently, the coretenance of the immune homeostasis in the body of a newborn child is secured by the whole immune complex feedback mechanisms, the most important among them are activation, proliferation and differentiation of cells-producers of antiinflammatory cytokines and the increase in the concentrations of anti-inflammatory mediators in the serum.
In mothers of children with IUGR with asphyxia, peripheral blood, a decrease of concentration of IL-4 is 2.3 times more in comparison with control group. In newborns with IUGR born with asphyxia there is a significant imbalance of pro-inflammatory (2.6 times increased
concentration of IL-1b, 1.7 times reduced concentration of IFN-y) and anti-inflammatory (2.3 times reduced concentration of IL-4) cytokines in peripheral blood serum.
The balance of pro- and anti-inflammatory cytokines, in the end, may be the key moment, causing the clinical condition of the child. Violation with the development of complications neonatal period can lead to clinical manifestation of the disease.
The conclusions: 1. It is established that the adverse pregnancy substantially determines the development of children in conditions ofchronic intrauterine hypoxia and birth with asphyxia. Among pathological conditions, along with hypoxic CNS effects and IUGR in newborn infants undergoing chronic intrauterine hypoxia more often respiratory disorders, intrauterine infection occure, and children who had asphyxia in the neonatal period, often develop pneumonia and acute inflammatory diseases. 2. Revealed that in children with IUGR born with asphyxia, in peripheral blood a decrease of concentration of IL-4 and anti-inflammatory.
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References:
1. Evsukova I. I. Pathogenesis of perinatal pathology of newborn children developed in a chronic hypoxia with placental insufficiency//Journal of obstetrics and feminine diseases. - 2004. - № 2. - P. 26-29.
2. Bose C., Van Marter L. J., Laughon M. et al. Fetal growth restriction and chronic lung disease among infants born before the 28th week of gestation//Pediatrics. - 2009. - Vol. 124. - № 3. - P. 458.
3. Koptseva A. V., Ivanov O. V., Vinogradov A. F. Peculiarities of the course of the period of adaptation and improvement of rehabilitation of premature infants with intrauterine growth retardation//Russian j ournal of Perinatology and Pediatrics. - 2008. № 3. - P. 23-32.
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5. Polin R. A., Spitzer A. R. Fetal and neonatal secrets. 2th.: Hanley &Belfus Publication. Philadelphia: 2006. -499 p.
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Frolova Tatyana Vladimirovna, Kharkov National Medical University, Doctor of Medical Science, Professor
E-mail: [email protected] Okhapkina Оlga Vladimirovna, Kharkov National Medical University, Doctor of Medical Science, Professor
Siniaieva Iryna Revazovna, Kharkov National Medical University, Associate Professor Tereshchenkova Iryna Ivanovna, Kharkov National Medical University, Associate Professor Atamanova Elena Vladimirovna, Kharkov National Medical University, Candidate of Medical Science
Modern aspects in the formation of health in child population
Abstract: Unfavorable state of the environment and worse social-economic conditions of life produce a significant negative effect on the formation of health of pupils.
Keywords: social-economic conditions, children’s health, mineral profile, physical development.
Sensitivity of the child’s organism to the effect of various factors causes flexibility of all physiological and pathological processes, which take place in the child’s organism. That is the state of health in childhood directly depends upon the influence of social, economic, ecological and other exo- and endogenous factors [1, 22-25].
The unsatisfactory state ofhealth in modern pupils is caused by a catastrophic reduction of physical load and motor activity of children, improper nourishment, chronic stresses and bad habits, the latter being widely common in adolescents at present.
As for the state of environment, according to data of the Ministry of Ecology and Natural Resources of Ukraine (2013), the content of harmful substances in the atmosphere of the City of Kharkiv exceeds their standard values 3.4- 5.4 times depending upon the City district. The discharge of harmful substances into the atmosphere is 356 000 tons; the air is polluted by 1200 enterprises and more than 500 000 vehicles [2].
The purpose of the study was to reveal the factors, which exert the largest influence on the formation of health in the child population of the Kharkiv Region.
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