The Role of Features of the Early Adaptation Period in Newborns of Mothers with Urinary System Pathology in the Morbidity and Mortality of Children

The dissertation is devoted to the study of the role of features of the early adaptation period in newborns of mothers with urinary system pathology in the morbidity and mortality of children. The relevance of the research is due to high rates of neonatal morbidity and mortality closely associated with disturbances of adaptive mechanisms, as well as the increase in urogenital pathology among pregnant women. The research has established that newborns of mothers with urinary system pathology constitute a risk group for the development of neonatal dysadaptation, high morbidity, and mortality, primarily of urinary system pathology. The presence of nephropathy in the mother has been recognized as one of the main risk factors for the occurrence of urinary system diseases in the newborn.

The research was carried out on the basis of a comprehensive approach encompassing clinical-laboratory, immunological, and morphological methods of study. For the first time, morphological analysis of biological fluids — urine by the "Lito-system," blood serum, and amniotic fluid — was applied for the assessment of the features of early adaptation in newborns with a complicated perinatal period. The informativeness of this method has been demonstrated during dynamic monitoring of the condition of pregnant women and newborns. Prognostic criteria for neonatal dysadaptation and principles for the formation of high-risk groups for the development of urinary system pathology in children have been developed.

The efficiency of functioning of organs and systems of the body is largely determined by the level of adaptation to changing conditions of vital activity under the influence of internal and external environmental factors. Adaptation represents such a structural-functional organization of physiological systems that ensures their most efficient functioning and interaction.

The shortest and most critical age period is the early adaptation period of the newborn, during which the formation of the body's own homeostatic regulatory system occurs (36, 46, 125, 198, 213, 255, 258, 270, 338).

The importance of studying the mechanisms of adaptation in newborns is due to high rates of early neonatal and infant morbidity and mortality, which are largely associated with the features of the response of the main physiological systems responsible for regulation of adaptation in the perinatal and neonatal periods (183, 168).

The application of new methods for diagnosing the morpho-functional state of organs and the female reproductive system during pregnancy, the fetus, and the newborn may contribute to solving the problem of studying the features of mutual influence of the maternal and fetal organisms within the mother-fetus functional system. Assessment of the final result of this system's activity, i.e., studying the features of the establishment of the child's homeostasis after birth, facilitates the prediction of disturbances in the physiological state of regulatory systems.

A distinctive feature of neonatal dysadaptation diagnosis is that its conduct must be based on comprehensive examination of not only children but also their mothers. Among the factors contributing to the impairment of early adaptation processes in newborns, identified through examination of mothers, the most important place is occupied by intrauterine fetal infection. The outcome of labor and the risk of pathology in newborns increase in the presence of both extragenital and urogenital maternal pathology, which poses a threat both to the course of pregnancy and labor and exerts a negative influence on the child's adaptation process (3, 5, 22, 35, 44, 63, 92, 107, 114, 124, 125, 147, 150, 172, 193, 239). It is known that in recent years there has been a trend toward an increase in urogenital pathology among pregnant women, and its negative influence on the child's health status is beyond doubt (78, 83, 85, 102, 121, 129, 173, 195, 200, 203, 236).

In the structure of child mortality from individual conditions arising in the perinatal period, intrauterine infections occupy a high proportion (8, 16, 28, 35, 44, 53, 58, 61, 106, 115, 129, 147, 150, 174, 184, 192, 194, 203, 220, 225). According to data from Malkova E.M. et al. (128), among newborns receiving treatment in neonatal pathology departments, children with intrauterine infection (IUI) constitute up to 80%. One of the frequent causes of IUI is considered to be the infectious-inflammatory pathology of the urinary system organs (USO) of pregnant women. The significance of USO pathology in pregnant women for the development of the dysadaptation syndrome in newborns is undeniable. Meanwhile, studies devoted to the problem of impairment of early adaptation in newborns and its relationship with USO pathology in pregnant women are rare, and their results are ambiguous, which dictates the necessity of more detailed study of this problem.

The prevention of ante-, intra-, and early postnatal pathology of the fetus and newborn occupies one of the leading places among the problems of modern pediatrics. The special role of the course of the early adaptation period in newborns in the formation of children's health is emphasized by the majority of authors (2, 9, 13, 15, 16, 21.30, 32, 52, 68, 84, 89, 107, 122, 140, 143).

The relevance of the problem is determined by the arising necessity of: identifying possible patterns of adaptogenic-protective reactions of the organisms of newborns and young children depending on the immunological reactivity of the mother during pregnancy, in particular, against the background of USO pathology; establishing the features of clinical-immunological reactions of newborns in the development of USO pathology; developing principles of prevention of neonatal pathology and criteria for predicting the occurrence and course of USO pathology in newborns. It is important to assess not only the early consequences of early dysadaptation but also its remote outcomes against the background of various therapeutic approaches, observation of children during follow-up, and tracking the formation of immune system functions in children who have experienced various USO diseases in the neonatal period.

Aim of the research

To establish possible patterns of the influence of the course of the early adaptation period on the morbidity and mortality of newborns of mothers with USO pathology, to develop criteria for early diagnosis and objective assessment of dysadaptation and prediction of diseases in newborns and young children.

Research objectives

1. To study the features of the course of a complicated perinatal period during clinical-laboratory monitoring of the condition of pregnant women and newborns.

2. To identify the features of adaptogenic-protective reactions of the organisms of newborns of mothers with USO pathology.

3. To study the indicators of clinical-immunological adaptation and intercellular interactions in newborns with USO pathology in the mother.

4. To determine the prognostic significance of clinical-laboratory indicators in the development of morbidity and mortality of newborns and young children.

0. To develop principles of prevention of neonatal pathology and criteria for the formation of high-risk groups of nephropathies in newborns and young children.

Scientific novelty

For the first time, the allocation of newborns of mothers with USO pathology into a risk group for the development of neonatal dysadaptation, high morbidity, and mortality has been scientifically substantiated. It has been established that the presence of nephropathy in the mother is one of the main risk factors for the occurrence of USO diseases in the newborn.

For the assessment of the features of early adaptation of newborns with a complicated course of the perinatal period, data on morphological analysis of biological fluids were used for the first time: urine by the Lito-system, blood serum, amniotic fluid. The informativeness of this method has been demonstrated during dynamic monitoring of the condition of pregnant women and newborns. During morphostructural analysis of urine, the greater part of hypoxic and ischemic lesions of the kidneys, sclerotic changes of renal tissue in newborns of mothers with pathological pregnancy and candidosis of the urogenital tract, both in mothers and in newborns, has been identified.

It has been established that in the early adaptation period of newborns of mothers with USO pathology, signs of both clinical and immunological dysadaptation are observed: an increase in serum concentrations of TNF-α not accompanied by an increase in serum concentrations of anti-inflammatory cytokines.

In more than two-thirds of newborns of mothers with USO pathology, mainly (56.5%), clinical manifestations of infectious-inflammatory diseases have been observed during the first three months of life.

The dynamics of changes in serum concentrations of cytokines, acute-phase inflammation proteins, and indicators of cellular and humoral immunity in the development of USO infection in newborn children have been characterized. It has been established that in the case of prenatal infection, cases of a more severe course of the infectious-inflammatory process in newborns predominate, which can be explained by an increase in the frequency of: suppression of the cellular link of immunity, decrease of the immunoregulatory index; decrease of prealbumin and α2-macroglobulin; low values of TNF-α and IL-4, increased concentrations of IL-8. A parallelism between a high frequency of viral infection and an increase in IL-12 has been noted.

It has been demonstrated that morphological markers of the structures of the solid phase of biological fluids can serve as indicators in the assessment of the state of adaptogenic-protective reactions of the newborn's organism, in particular the adequacy of the cellular immune response. It has been established that the detection of atypical and incomplete forms of anisotropic spherolytes in the absence of basic morphotypes in the fractions of blood serum and amniotic fluid is one of the informative arguments of reduced immunological protection. Adequate indicators of cellular immunity in healthy newborns were combined with an expanded spectrum of basic morphoforms with a clearly symmetrical structure.

Prognostic criteria for neonatal dysadaptation in newborns of mothers with USO pathology and principles for the formation of high-risk groups for the development of USO pathology in children have been developed.

Practical significance

It has been established that newborns of mothers with USO pathology constitute a risk group for the development of neonatal dysadaptation, high mortality, and morbidity, primarily of USO pathology.

The most informative clinical-laboratory indicators facilitating the prediction of disturbances in neonatal adaptation processes and contributing to the early diagnosis of USO pathology in newborns have been identified: monitoring the health status of pregnant women in the third trimester, analysis of morphotypes and structural formation of urine, blood, and amniotic fluid, determination of prealbumin, C-reactive protein, β2-microglobulin, indicators of the cellular link of immunity with phenotyping of lymphocyte subpopulations.

It has been shown that the greater part of the increase in β2-microglobulin and the decrease in prealbumin are characteristic of newborns with an infectious-inflammatory process against the background of intrauterine fetal infection. Parallel increase of CD4+ and CD8+ lymphocyte fractions, decrease of CD4+, and often increase of NK and CD19+ content precede the infectious-inflammatory process occurring in the postnatal period.

Morphological indicators of biological fluids — markers of predisposition to dysadaptation in newborns and young children — have been characterized, and their relationship with the degree of disturbances in the cellular and humoral links of immunity has been determined.

A principle for the formation of high-risk groups for the development of USO pathology has been developed and introduced into practice, using a complex of modern, accessible, and informative methods for assessing the state of adaptogenic-protective reactions of the newborn's and infant's organism.

Main propositions for defense

In women with USO pathology, labor pathology is aggravated and the physiological course of early adaptive mechanisms in newborns is impaired. In the predominant majority of newborns of women with USO pathology, chronic intrauterine hypoxia or acute asphyxia during labor is detected, pronounced neonatal dysadaptation is reliably increased, and perinatal lesions of the nervous system of varying degrees of severity are observed in all newborns. In pregnant women with USO pathology, cases of fetal death are significantly more frequent, and mortality among newborns at birth or during the first days of life is high.

Data on the morphology of biological fluids: a significant decrease in the frequency of basic morphotypes and an increase in pathological structures in the fractions of blood serum of women with USO pathology, the appearance of pathological striated structures, semicircular and ring types of cracks in the urine fractions; predominance of spider-like, plate-like morphotypes and structures specific to tissue intoxication and necrosis in the amniotic fluid fractions — are associated with a disturbance of the adaptive reactions of the organism of these women and predict the impairment of neonatal adaptation processes and the development of pathological processes in newborns.

Morphological markers of the structures of the solid phase of biological fluids can serve as indicators in the assessment of the state of adaptogenic-protective reactions of the newborn's organism, in particular the adequacy of the cellular immune response.

Intense functioning and exhaustion of the reserves of the immune system in newborns of mothers with USO pathology in the early neonatal period manifests as a decrease in the number of leukocytes, neutrophils, eosinophils, and lymphocytes (decrease of the total leukocyte count, CD4+, decrease of the immunoregulatory index) of peripheral blood. The development of dysadaptation is accompanied by an increase in the proportion of antigen-presenting cells of peripheral blood (monocytes). A decrease in prealbumin, an increase in haptoglobin, C-reactive protein, C4 complement component in umbilical cord blood, as well as an increase of M in peripheral blood on the 4th to 7th day of life possess the greatest diagnostic value in predicting pronounced dysadaptation in newborns of mothers with USO pathology.

Signs of tubular and glomerular dysfunction and a tendency toward the development of USO pathology in newborns of mothers with USO pathology are indicated by an increase in the level of β2-microglobulin in urine and blood. A pathological course of the early postnatal adaptation period is preceded by an increase in IL-4, IL-12 in peripheral blood, and IL-8 in umbilical cord blood of newborns. A decrease in the apoptosis realization index (ARI) in peripheral blood over time is an informative indicator for predicting impairment of the early adaptation period.

The presence of nephropathy in the mother is one of the main risk factors for the occurrence of USO diseases in the newborn. The identification of very high, high, and moderate risk groups makes it possible to establish the probability of the development of neonatal dysadaptation and USO pathology in newborns.

Monitoring the health status of pregnant women in the third trimester, analysis of morphotypes and structural formation of urine, blood, and amniotic fluid are informative clinical-laboratory indicators facilitating the prediction of disturbances in neonatal adaptation processes and the development of USO pathology in newborns and young children. The developed complex of clinical-laboratory, immunological, and morphological tests is a criterion for predicting the course of neonatal adaptation, morbidity, and mortality of newborns of mothers with USO pathology.

Implementation in practice

The results of the research have been introduced into the practice of the pediatric resuscitation department of the City Medical Center (Dushanbe), the neonatal department of the Research Institute of Obstetrics, Gynecology and Pediatrics of the Ministry of Health of the Republic of Tajikistan; into the educational process of the departments of children's diseases No. 2 of RSMU (Moscow), children's diseases No. 1 and propaedeutics of children's diseases of the Tajik State Medical University (Dushanbe).

Publications and testing of the work. The main provisions of the dissertation work have been reported and discussed at: the IV Congress of the Association of Cardiologists of Central Asia, Bishkek, 2002; the Annual Scientific-Practical Conference of TGMU, Dushanbe, 2002; the 50th Annual Scientific-Practical Conference of TGMU, Dushanbe, 2003; the 51st Annual Scientific-Practical Conference of TGMU "Water and Human Health", Dushanbe, 2003; the Republican Conference of Biochemists, Dushanbe, 2004; at the meeting of the expert commission on therapeutic disciplines, Dushanbe, 2005.

Thirty-two printed works have been published on the topic of the dissertation. Two methodological recommendations and an instruction on improving the system of birth registration and perinatal mortality accounting have been developed, tested, and introduced into practice.

Volume of the work. The dissertation is presented on 201 pages of computer text, consists of an introduction, 8 main chapters, conclusion, findings, practical recommendations, and a list of references; contains 26 tables and is illustrated with 10 figures. The bibliography includes 353 sources, of which 182 are foreign.