Features of Early Postnatal Adaptation of Newborns of Mothers with Arterial Hypertension

The dissertation is devoted to the study of the features of early postnatal adaptation of newborns born to mothers with arterial hypertension. The research covers issues of epidemiology, pathogenesis, and classification of arterial hypertension in pregnant women, the impact of intrauterine hypoxia and intranatal stress on the fetus and newborn, as well as cardiovascular system adaptation, cerebral blood flow, and structural changes of the brain in the early neonatal period. Special attention is given to the hemodynamic and metabolic aspects of adaptation.

The work is aimed at comprehensive examination of central and cerebral hemodynamics, the enzymatic status of peripheral blood lymphocytes, and structural changes of the brain in newborns of mothers with arterial hypertension. The objective is to study the course of the early neonatal period and adaptive processes for the optimization of diagnostic measures, including the development of prognostic algorithms that allow timely identification of the risk group of newborns and prevention of complications.

1. Relevance of the problem. Fetal and neonatal pathology determines both the postnatal development of the child and the health of the adult [14, 39, 76, 113]. In the structure of perinatal morbidity and mortality, obstetric and extrauterine pathology plays a major role. It is evident that reducing morbidity and mortality of the fetus and newborn is one of the most important medical and social problems [14, 19, 33, 39, 123, 195]. Diseases of the cardiovascular system are the most frequently encountered group of extrauterine diseases in pregnant women and one of the leading causes of maternal and perinatal mortality [123, 167, 169, 198]. In the structure of cardiovascular pathology in pregnant women, arterial hypertension (AH) occupies a leading position [3, 35, 99, 154, 137, 198]. The causal relationship between morbidity in pregnant women and their newborn children is beyond doubt [123, 162, 198]. A vicious circle is created: sick mother - sick child - sick adolescent - sick mother [34, 35, 177]. The level of perinatal morbidity associated with AH in our country ranges from 463.0 to 780.0 per mille [146, 196]. A frequent complication of pregnancy in the presence of AH is the development of fetoplacental insufficiency (FPI), which is considered one of the leading causes of perinatal morbidity and mortality [1, 48, 52, 97, 145, 162, 205]. Neonatal morbidity in AH in pregnant women accompanied by FPI reaches 74-100% [162]. It should be noted that the obstetric aspect of research on this problem is limited to studying the course of pregnancy, the moment of delivery, and at best, a very brief characterization of the newborn at birth [52, 61, 137]. The features of further development of newborns born to mothers with AH are insufficiently studied, which limits the possibility of providing qualified care to these children, both during the neonatal period and in subsequent years [61, 150, 173]. The problem of health of newborns and young children is very closely related to one of the key concepts in medicine and biology — adaptation, which constitutes "an inseparable attribute of all living things and is characterized by the same diversity as life itself" [77]. At the present time, it should be considered proven that the very concept of "health status" cannot be considered without taking into account the features of adaptation of the organism to environmental conditions [34, 80, 101, 115]. It is from the position of adaptation that the main tasks of pediatrics and perinatology can be resolved: disease risk prediction, preventive therapy, prophylaxis, health promotion, and treatment [5, 18, 39, 101]. The early neonatal period is the first of the critical periods of postnatal ontogenesis, identified by Yu.I. Vel'tishchev et al. as early as 1983 [77]. In addition to a global restructuring of hemodynamics, metabolism is substantially altered, the coupling of anaerobic glycolysis and oxidative phosphorylation processes occurs, and the body's own thermoregulation, digestion, and ion homeostasis regulation systems are engaged [77]. Adaptation disorders in the early neonatal period have a significant impact on the child's health and subsequent development. Childbirth and the early neonatal period of life represent a unique combination of extreme impacts, requiring a continuous change in adaptation mechanisms at different levels of self-regulation [194]. The wide range of parameter fluctuations in the same child during overall adaptation is an indicator of high reserve capabilities, but this does not allow the formulation of a single concept of newborn adaptation and complicates the interpretation of examination results. One of the main parameters of newborn adaptation to extrauterine conditions is the restructuring of the circulatory system [10, 16, 44, 49, 63, 80, 115, 135]. The colossal changes occurring in the central hemodynamic system immediately after birth entail changes in cerebral blood flow and the peripheral component of the circulatory system. In our work, we focused primarily on the hemodynamic aspect of adaptation and only slightly touched upon the problem of metabolic adaptation in the newborn, without addressing many other aspects. This is because the concept of "adaptation" itself is very broad and encompasses such an enormous number of parameters that it is simply impossible to illuminate all aspects of adaptation within a single work. It should also be noted that many changes in hemodynamic and metabolic status in the early neonatal period have a compensatory-adaptive character. Therefore, most disorders arising during the early postnatal adaptation period are transient and reversible. The newborn organism has enormous reserve capabilities and can quite cope with many problems arising in the early neonatal period on its own. However, there are situations where medical intervention is necessary as early as possible, even in the preclinical period of development of a pathological condition. This makes it possible to use optimal therapeutic tactics and avoid severe consequences for the newborn and their family, both in the medical and social sense. This applies especially to neurological disorders, which are the leading cause of disability among the child population of Russia [14, 66, 126]. In this respect, the significance of modern methods of functional diagnostics for early detection of cerebral circulation disorders cannot be overstated. However, despite a large number of works [4, 14, 29, 33, 37, 41, 51, 64, 65, 67, 79, 94, etc.] devoted to this problem, the interpretation of examination results of newborns to this day remains difficult. This is due to the fairly wide range of normative values of cerebral blood flow parameters in newborns, as well as the insufficient individual approach to diagnostic questions for this particular child. At the current stage of clinical medicine development, the development of mathematically substantiated diagnostic and prognostic algorithms becomes relevant. This applies especially to conditions of the early neonatal period, when many diseases have nonspecific symptoms and a "blurred" clinical picture. In this period, it is sometimes very difficult to conduct differential diagnosis between normal adaptive changes in the newborn organism and the onset of a pathological process that may subsequently have catastrophic consequences. Medical intervention during the early postnatal adaptation period should be evidence-based and timely, and to solve this task, diagnostic algorithms should be developed for all groups of newborns, especially for children from pregnancies with high perinatal risk.

2. Research objective: to study the features of the course of the early neonatal period, hemodynamic and metabolic adaptation of newborns of mothers with AH for the optimization of diagnostic measures.

3. Research tasks:

1) Assess the features of the course of the perinatal period and the health status of newborns of mothers with AH.

2) Study the features of central and cerebral hemodynamics and the status of the enzymatic status of peripheral blood lymphocytes in the group of newborns of mothers with AH during the first week of life.

3) Determine the relationship between hemodynamic and metabolic indicators and their correlations with anamnestic and clinical-laboratory characteristics during the early neonatal period.

4) Based on sequential Wald analysis, identify a "risk" group of newborns for the development of intraventricular hemorrhage.

4. Scientific novelty.

For the first time, a comprehensive examination of central and cerebral hemodynamics, structural changes of the brain, and the enzymatic status of peripheral blood lymphocytes has been carried out among newborns of mothers with AH.

For the first time, features of cellular energy metabolism, central hemodynamics, and cerebral blood flow have been identified in the group of newborns of mothers with AH.

In the first days of life, activation of oxidative-reductive processes and an increase in hemodynamic indicators have been observed, followed by their decrease by the end of the early neonatal period, which indicates depletion of the reserve capabilities of the newborn organism.

The influence of hemodynamic and metabolic changes on the course of the early neonatal period in this contingent of children has been demonstrated.

The relationship between different links of hemodynamic and metabolic adaptation and their partial interdependence have been shown.

Based on clinical and anamnestic data and hemodynamic parameters, an algorithm for predicting the possible development of intraventricular hemorrhage in newborns whose mothers suffer from AH has been compiled and analyzed for the first time.

5. Practical significance and implementation of results.

The adverse influence of arterial hypertension in pregnant women on the course of the early neonatal period in the newborn has been proven.

Differences in central and cerebral hemodynamic indicators have been identified that allow suspicion of cerebral circulation disorders in children born to mothers with AH, and with constant dynamic monitoring of these parameters, the disruption of adaptive mechanisms can be prevented.

Features of the cytochemical profile of peripheral blood lymphocytes in the group of newborns of mothers with AH have been identified, which can be used for the development of metabolic therapy for this contingent of children.

A risk group of newborns of mothers with AH for the development of intraventricular hemorrhage has been identified.

A prognostic program for the development of intraventricular hemorrhage in newborns whose mothers suffer from AH has been compiled for the practicing physician, which will allow timely preventive measures to be taken to prevent this complication.

6. Main provisions for defense:

1. Arterial hypertension in pregnant women adversely affects intrauterine fetal development and reduces the adaptive capabilities of the newborn organism.

2. In newborns born to mothers with AH, tension of compensatory-adaptive mechanisms is observed on the first day of life, which by the end of the early neonatal period is replaced by depletion of the organism's reserve capabilities.

3. The period of early postnatal adaptation in newborns whose mothers suffer from AH is characterized by specific changes in central and cerebral hemodynamics and the enzymatic status of lymphocytes, which dictates the necessity of observing these children in a risk group for the development of cerebral circulation disorders.

7. Testing of the work.

The materials of the dissertation were reported at the II Inter-university Conference of Young Scientists and Students "Actual Medical and Biological Problems" (Izhevsk, 2002), the I International Conference "Early Stages of Pregnancy: Problems, Solutions, Prospects" (Moscow, 2002), the IX Russian National Congress "Man and Medicine" (Moscow, 2002), the IV Russian Forum "Mother and Child" (Moscow, 2002), the All-Russian Scientific and Practical Conference "Second Tula Pediatric Readings" (Tula, 2003), the I Congress of Cardiologists of the Volga and Ural Federal Districts of the Russian Federation (Perm, 2003), the IV Inter-university Conference of Young Scientists and Students (Izhevsk, 2004), the V International Seminar "Angioplasty and Stenting of Coronary Arteries in the Treatment of Ischemic Heart Disease" (Izhevsk, 2003), the IX Congress of Pediatricians of Russia "Actual Problems of Pediatrics" (Moscow, 2004), at the joint meeting of the problem commission of the pediatric faculty and the departments of pediatrics, pediatric infections with a course of pediatric diseases, pediatrics and pediatric infections of the Faculty of Advanced Training and Professional Development, propedeutics of pediatric diseases with a course of polyclinic pediatrics, obstetrics and gynecology of the Faculty of Advanced Training and Professional Development of Izhevsk State Medical Academy of the Federal Agency for Healthcare and Social Development.

8. Implementation in practice.

The results of the work have been implemented in the practical activities of the newborn department and the department of resuscitation and intensive care of newborns of Maternity Hospital No. 6 in Izhevsk, the ultrasound diagnostics department of Republican Clinical Hospital No. 3, the resuscitation department of the Republican Pediatric Clinical Hospital, and in the educational process of the Department of Pediatrics of the State Educational Institution of Higher Professional Education "Izhevsk State Medical Academy" of the Federal Agency for Healthcare and Social Development.

9. Publications.

Fifteen printed works have been published on the topic of the dissertation.