At present, there is a significant prevalence of manifestations of reactive asthenic syndrome in children as a result of stress on the adaptive capabilities of the body due to prolonged living under the stress of military hostilities.

The main pathogenetic mechanism of reactive asthenic syndrome is the overload of the activating reticular formation, which synchronizes all aspects of human behavior and manages its energy resources. A "vicious circle" is formed when the body needs additional energy to overcome external influences (somatic, infectious, stress overloads, etc.), and internal resources are not ready to accept and process it. The appearance of clinical symptoms is a signal of overload of the reticular activating system, autointoxication with metabolic products, and dysregulation of the production and use of energy resources of the body [1].

In addition, disorders of the digestive system are also characterized by the transient nature of asthenic syndrome in children and the presence of a clear connection with the provoking factor and its nonspecificity1.

A significant factor provoking the development of reactive asthenic syndrome in primary school children is a deficiency of vitamins and minerals, individual amino acids, in particular, tryptophan and polyunsaturated fatty acids, which are necessary for the normal functioning of the nervous system and the synthesis of neurotransmitters that affect the emotional sphere and behavior of the child2. The emotional characteristics of primary school children are characterized by diversity, short duration of manifestations, and at the same time a combination of intensity and stability of negative emotions. Different negative emotions (despair, fear, anxiety, melancholy) are accompanied by the same type of visceral shifts. The excitability of the sympathoadrenal system increases, therefore, the secretion of catecholamines increases. The link between the psychological and somatic spheres is the stress of warfare, expressed mainly in the form of longing and constant anxiety, a neurovegetative-endocrine motor response, and a characteristic sense of fear. Defensive physiological mechanisms only partially reduce, not completely eliminate, these phenomena. As a result, the pathogenic effect of stress on the child's body increases. This process can be considered as pathophysiological inhibition: stimuli coming from the central nervous system are blocked and diverted to visceral structures through the ans, leading to changes in various organ systems3. In the presence of pathoplastic overstrain, which is not blocked by psychological protection, the functional stage of the lesion develops into destructive morphological changes in the somatic system and generalization of the disease occurs.

The deficiency of macro- and micronutrients in children who have been exposed to the armed conflict zone is associated with malnutrition, which, of course, occurred during the child's long stay in closed premises (basements and bomb shelters) with a rather meager and monotonous diet. Nutrient deficiency also develops as a result of impaired digestion of food, diseases of the gastrointestinal tract, dysbiotic intestinal disorders, and metabolic pathology [2].

The purpose of the study is to study the peculiarities of the digestive system in children with reactive asthenic syndrome and the correction of disorders using a comprehensive integration program.

A prospective cohort non-randomized study was conducted from April 2022 to November 2022 (inclusive) on the basis of the Federal State Budgetary Educational Institution of Higher Education St. Luke Lugansk State Medical University (rector — Doctor of Medical Sciences A.V. Torba) with the participation of the Department of Pediatrics and Childhood Infections (head of the department — Doctor of Medical Sciences, prof. I.B. Ershova), State Budgetary Health Care Institution "Lugansk City Children's Hospital No. 3 of the Lugansk People's Republic (LPR)" (Chief Physician — Candidate of Medical Sciences S.Yu. Kozina), State Institution “Lugansk Republican Children's Clinical Hospital” of the LPR (Chief Physician — L.M. Beletskaya), State Institution Lugansk State Pedagogical University of the LPR of the Institute of Pedagogy and Psychology (Director — M.V. Rud) with the participation of the Department of Defectology and Psychological Correction (Head of the Department — Candidate of Medical Sciences I.I. Chubova), State Budgetary General Education Institution of the LPR "Lugansk secondary school No. 26" (Director — T.E. Vasilina), State Budgetary General Educational Institution of the LPR "Pervomayskaya Secondary School No. 30 named after E. Oleynikov" (Director — E.A. Bezkorovainyi), Children's City Polyclinic of the Zheleznodorozhny District of Rostov-on-Don (Municipal budgetary healthcare institution "Children's City Polyclinic of the Zheleznodorozhny District of Rostov-on-Don") (Chief Physician — A.M. Candidate of Medical Sciences Levchin), Municipal Budgetary General Education Institution of the city of Rostov-on-Don: "School No. 64" (Director — I.P. Ponomareva), "School No. 67" (Director — N.E. Sysoeva).

The protocol and study design were approved by the Local Ethics Committee, the Academic Council of Federal State Budgetary Educational Institution of Higher Education St. Luke Lugansk State Medical University on September 9, 2021.

The study included 419 children of primary school age, who were divided into groups and subgroups depending on the place of residence (Table 1).

Grade schoolers of the main group were included in the comprehensive rehabilitation integration program, which was carried out for children of the I "a" subgroup in Rostov-on-Don, for children of the II "a" subgroup — on the territory of the LPR. The program included interdepartmental interaction of medical and psychological-pedagogical specialists, as well as specialists in social services. Medical observation was carried out according to an individual plan with each child in accordance with the state, as well as health indicators, and included a systematic diagnostic examination with recording of the results, which served as the basis for the organization and formation of rehabilitation activities by a team of specialists. The tasks of the psychological and pedagogical unit were to assess the level of psychophysical development of the child, taking into account the individual characteristics and the organization of the child's individual educational route. Accompanying social workers provided social and legal support, the development of opportunities to overcome problems, and assistance in solving social security issues.

Full examination of children was carried out before the start of the comprehensive integration program and 6 months after the start of its implementation.

The comprehensive integration program included general health measures: the daily regimen was adjusted, nutrition was optimized, and daily walks lasting 1–2 hours were introduced into the daily routine. A set of morning gymnastics exercises was developed for children. In a differentiated mode, ultra-high-frequency therapy, balneotherapy, halotherapy, restorative massage, and light therapy were prescribed. Psychological correction was carried out aimed at correcting negative character traits, overcoming fears, and normalizing the psycho-emotional state. Working with parents contributed to the creation of a favorable psychological atmosphere in the family and an attentive and respectful attitude toward the child on the part of parents.

The above-described measures were carried out against the background of taking the vitamin-mineral complex Complivit Active one tablet once a day after a meal with sufficient liquid.

The optimally selected composition of the active substances included in this vitamin-mineral complex makes it possible to optimize the neurovegetative status of children with asthenic syndrome and the condition of the digestive tract.

Thus, the components of the complex are necessary to optimize the state of the digestive tract, as well as the mnestic functions and intelligence of the child under mental stress, and to support the nervous system during stress.

In addition, a combination of monotherapies L-carnitine and ubiquinone was prescribed in children with hypersthenic asthenia, the manifestations of which were observed in the form of increased fatigue, reduced performance, hyperesthesia combined with excessive irritability, excitability and overexcitability, motor activity, sleep disorders and headache, minimal age-related doses of carnitine (from the range: elcar, carnitene, carnitone, carnitine chloride): 25–30 mg/kg/day for a month, after which the doses were increased to average therapeutic, namely: 45 –50 mg/kg/day with their use up to 3–6 months. Coenzyme Q10 (Qudesan) was given in average therapeutic doses (from 3 mg/kg/day) for a month, after which the doses were reduced to prophylactic, namely 2 mg/kg/day [3, 4, 5].

In children with hyposthenic asthenia, when registering complaints of weakness, lethargy, fatigue, reduced activity, apathy, lethargy, and daytime drowsiness, therapy with these drugs began with high age-related doses of L-carnitine (75–100 mg/kg/day for a month), after which they switched to the use of medium-therapeutic, namely 45–50 mg/kg/day with their use up to 3–6 months, depending on the condition of patients. Coenzyme Q10 was started with average therapeutic doses of 3 mg/kg/day for a month, after which the doses were reduced to prophylactic, namely 2 mg/kg/day. The rationale for the use of antioxidants, in particular coenzyme Q10, in children who have experienced stress from warfare was that the mechanisms of antioxidant protection in children are imperfect, therefore lipid peroxidation poses a special danger to them. The immaturity of the physiological and metabolic systems of the child's body causes a high ease of their violation under the influence of various adverse environmental factors, in particular in a stressful situation.

Inclusion criteria in the main group:

- children of primary school age (from 7 to 10 years inclusive);

- children living in the territory of active hostilities in the territory of the LPR (Pervomaisk);

- signed informed consent of parents/legal representatives of the child to participate in the study.

Inclusion criteria in the control group:

- children of primary school age (from 7 to 10 years inclusive);

- children not residing in the territories of active hostilities;

- signed informed consent of parents/legal representatives of the child to participate in the study.

All children underwent a collection of complaints, anamnesis, analysis of outpatient charts, objective examination, and study of the motor-evacuation function of the gastrointestinal tract (peripheral electrogastroenterography) [6]. The work used "Gastroscan-GEM", created by the Istok-Sistema Research and Production Enterprise in Fryazino.

Mathematical processing was carried out using the Statistica software package for Windows 7.0. To compare qualitative indicators, the average value (M) and the standard deviation (σ) were calculated. Differences were considered statistically significant at p<0.05 (95% significance level) and at p<0.01 (99% significance level). To establish the relationship between the studied indicators, a correlation analysis was used with the calculation of the Pearson correlation coefficient.

During the dispensary observation of children in the zone of armed conflict, a particularly high frequency (in 100% of children) of complaints related to the digestive system was noted. In this regard, a more detailed study was conducted in this direction.

Further research was aimed at analyzing outpatient records and a more detailed examination of grade schoolers in terms of the frequency of registration of functional and organic pathology on the part of the digestive system (Table 2).

Our further study was aimed at studying the motor-evacuation function of the gastrointestinal tract, by determining the myoelectric activity of its different parts (Table 3).

The obtained data indicate a redistribution of relative electrical activity in different parts of the gastrointestinal tract of children of the main group on an empty stomach.

Conducting a comprehensive integration rehabilitation program had an optimizing effect on the motor-evacuation function of the gastrointestinal tract of children of the main group. There was a decrease in the relative power of the stomach, duodenum, jejunum, and ileum against the background of an increase in the projection of the colon on an empty stomach in a subgroup of grade schoolers evacuated to Rostov-on-Don (I "a"). In the subgroup of children remaining in the territory of the LPR (II "a"), a similar trend was observed, except for the values of the duodenum, which, despite the decrease, did not have a statistically significant difference from the indicator before the start of rehabilitation measures.

After eating, on the contrary, an increase in myoelectric activity was recorded in relation to all indicators of the gastrointestinal tract in grade schoolers of the I "a" subgroup, which made them comparable to the values of the control II "b" subgroup already 6 months after the start of the rehabilitation program. In children of the II "a" subgroup (remaining in the LPR), despite the increase in postprandial indicators, the values of the stomach, duodenum, jejunum, and colon after 6 months did not reach the level of the corresponding control subgroups and had a statistical difference with the I "a" subgroup. In response to the food load, the myoelectric activity of the stomach and duodenum in the II "a" subgroup increased by less than 1.5 times. To normalize their levels, in our opinion, this subgroup needs a longer recovery period.

The analysis of the rhythmicity coefficient characterizing the contractions of various parts of the gastrointestinal tract revealed the following (Table 4).

The implementation of comprehensive rehabilitation measures led to a decrease in the level of the rhythmicity coefficient before meals in the main group to values comparable to the indicators of the corresponding subgroups. It should also be noted that in the I "a" subgroup, postprandial indicators began to correspond to the normative growth (1.5–2.0 times) in comparison with the values before meals and had a statistical difference with the levels in the 1st study. In contrast to the I "a" subgroup, in the II "a" subgroup, despite the rehabilitation measures, the postprandial increase did not reach the standard values in the duodenum and ileum.

The study of the ratio (Pi/Pi+1), reflecting the ratio of the electrical activity of the overlying department to the underlying department, which means the coordination of contractions of the neighboring gastrointestinal tract, also revealed deviations in comparison with the control group for some clusters. Thus, the analysis of indicators at the first examination after eating reflected the lack of coordination of the functional activity of the stomach, duodenum, jejunum, and ileum with other departments in response to the food load. This was expressed by postprandial insufficiency of electrical activity in comparison with fasting values (from (–) 1.3 to (+) 1.15 instead of (+) 1.5 – (–) 2.0) (Table 5).

In addition, the ileum had increased pre-prandial ratios in grade schoolers who experienced war stress in comparison with control subgroups.

The analysis of the data obtained during the dispensary observation showed the following. In the survey, appetite disorders were most often recorded. Moreover, out of 97 children, 69 (71.13%) showed a decrease, and 28 (28.87%) — a complete absence. In addition, in 51 (52.58%) of 97 children, appetite impairment was accompanied by nausea, and in 44 (45.36%) — by periodic vomiting.

The second ranked place in the frequency of complaints from the digestive tract was taken by the violation of the stool (79 (61.72%) of grade schoolers). Moreover, constipation and diarrhea were recorded with the same frequency of 41 (51.90%) and 38 (48.10%) children, respectively, of the above groups.

One in three children had recurrent abdominal pain. A more detailed survey revealed that most often children indicated pain in the umbilical cord (17 (41.46%) people), as well as in the epigastric (14 (34.15%) children) areas. The majority (68.29%) of children had weekly (even daily) pains that disappeared during switching of attention or in a calm environment. 

Analysis of the data obtained from outpatient records showed that in general, functional abnormalities in the digestive system were recorded in 79 (61.72%) of the examined children, and organic pathology — in 62 (48.44%). Twenty-eight (21.88%) grade schoolers had somatoform disorders of the gastrointestinal tract. A combined pathology of the digestive system was observed in 97 (76.98%) children.

Among the functional deviations in the examined children, the first ranked place was occupied by functional disorders of the biliary tract (80 (62.50%) of the examined children) (Table 2). At the same time, our data coincide with the indicators of other authors, indicating that disorders of the biliary tract are one of the most common forms of functional disorders in children (ICD = 10 K 82.8; Rome III E1–E3, Rome IV E1–E2) [7]. Most studies have shown that these disorders develop as a result of discoordination of the "brain-gastrointestinal tract" interaction, namely: the central nervous system, the ans, and motor-tonic function of the components of the biliary tract, which entails functional disorders at the beginning, and subsequently — diseases of organic pathology.

The second ranked place among the dysfunctions of the digestive system was occupied by defecation disorders, which occurred in more than 40% of children. Moreover, if according to the results of studies conducted by other authors, constipation prevailed in the general population of primary school children [8, 9, 10], then our observation of children in the zone of armed operations allowed us to identify the registration of constipation and diarrhea with the same frequency: 24 (46.15%) and 28 (53.85%), respectively.

The third rank among the functional disorders of the digestive system in children in the zone of the military operation was occupied by recurrent abdominal pain (40 (31.25%) people), which can cause distress and discomfort in children, and also, according to the Roman criteria of the IV revision, like other functional gastrointestinal disorders, have a genesis in the gut-brain interaction disorder.

Among the organic diseases of the digestive system in the first place in primary school children living in zones of active hostilities, there were diseases of the stomach and duodenum (in 59 (46.09%) of those examined). Moreover, among them, gastritis and gastroduodenitis were in the lead (in 44 (74.58%) children).

The next ranked place was occupied by intestinal diseases. Among these, nonspecific ulcerative colitis (NUC) was the leading cause, accounting for 72.72% (24) of grade schoolers with bowel disease overall. The level of activity, according to the survey, ranged from minimal (10–34 points) to moderate (35–64 points) on the scale of the pediatric index [11]. In addition to NUC, non-infectious gastroenteritis, unspecified colitis, Crohn's disease, diverticulosis, etc. were recorded with a lower frequency.

Significantly less often (19 (14.84%) people) in the examined children, diseases of the gallbladder and bile ducts were recorded, which were represented by chronic cholecystitis, cholangitis, and congenital defects of the bile duct system; one child was diagnosed with cholelithiasis.

The rest of the organic diseases of the digestive system occurred with the same frequency, which is presented in the table.

It is necessary to note the high registration of the presence of several diseases of the digestive system in the same children at the same time.

It should be noted that the study we conducted in 2014–2016 regarding the state of health of children in the frontline areas [12, 13, 14], in comparison with the currently presented data (since the beginning of the intensification of hostilities in 2022) demonstrated a sharp deterioration in indicators of diseases of the digestive system.

Conducting a comprehensive integration rehabilitation program made it possible to reduce the frequency of registration of functional deviations in both subgroups, both for individual indicators and as a whole: in the I "a" subgroup — by 1.79 times, and in the II "a" — by 1.59 times (p<0.01).

In children evacuated to Rostov-on-Don of the I "a" subgroup, the frequency of occurrence of all diagnosed categories of functional disorders of the digestive system decreased.

In children who remained in the territory of the LPR, despite the decrease in indicators under the influence of rehabilitation measures, a statistically significant level of decrease was observed only in relation to defecation and biliary tract disorders (p<0.05).

Assessment of the dynamics of organic pathology of the digestive tract in children of the examined subgroups revealed a not so pronounced effect of the comprehensive integration rehabilitation program carried out in comparison with the indicators of functional deviations. The frequency of registration of organic diseases in the I"a" subgroup (evacuated children) decreased by 45.15%, and in the II"a" subgroup (remaining on the territory of the LPR) — by 31.15%.

A more detailed analysis of certain categories of diseases made it possible to establish that in the I "a" subgroup, the incidence of diseases of the stomach and duodenum decreased by 1.8 times, and the incidence of diseases of the intestine by more than 2 times (p<0.05). In the II "a" subgroup, the incidence of diseases of the stomach and duodenum decreased by 1.6 times (p<0.05). The frequency of intestinal diseases, despite the decrease, did not reach a statistically significant difference from the indicators established in May.

The analysis of the indicators of the motor-evacuation function of the gastrointestinal tract, by determining the myoelectric activity of its different parts, revealed an increase in the relative power (Pi/Ps) in almost all parts of the gastrointestinal tract (except for the colon) in children in conditions of active hostilities. In parallel, we noted a decrease in the myoelectric activity of the colon (by 31.29% compared with the control group), indicating a slowdown in its motility (Table 3).

The study of the relative power after eating revealed an inadequate postprandial change in the indicators. If normally, in response to the food load, the myoelectric activity of the gastrointestinal tract should increase by 1.5–2 times, then in children in the zone of armed conflict, the values increased only by 10–15% or did not change at all.

Kritm indicators of the stomach, duodenum, and ileum at the first examination on an empty stomach in children living in the shelling area were increased in comparison with the corresponding control subgroups (Table 4). After the food load in this group of children, there was no adequate increase in the indicators in all parts of the gastrointestinal tract, which in comparison with the values of fasting increased by 1.10–1.3 times instead of the normal 1.5–2 times.

The results of the repeated examination after 6 months showed that the development and implementation of a comprehensive rehabilitation program increased the efficiency of the gastrointestinal tract, which was reflected in the optimization of the coordination of its various departments. However, if the pre-/postprandial ratios in the I "a" subgroup of the main group were leveled to 1.5–2 in all parts of the gastrointestinal tract, then in the II "a" subgroup of the same group, despite the increase in values in the duodenum and jejunum, they were kept at the level of 1.3–1.4, which is statistically lower in comparison with the corresponding control subgroup.

At the end of the study, based on the results of the correlation analysis with the calculation of the Pearson correlation coefficient, we studied the relationship between the individual indicators.

As a result of mathematical processing, a positive correlation was established between the presence of nausea/vomiting and the level of Pi/PS of the stomach (r=+0.78; p=0.021), between the presence of diarrhea and the Kritm value of duodenum (r=+0.69; p=0.019), the frequency of functional abdominal pain disorders and the myoelectric activity of the jejunum (r=+0.81; p=0.010). In addition, a negative correlation between the postprandial level of Kritm of the colon and the severity of constipation (r=-0.72; p=0.001) was revealed.

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