Laboratory markers for predicting critical obstetric conditions

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Abstract

Objective. To identify early laboratory markers of the risk for developing critical obstetric conditions (COC).

Materials and methods. As a retrospective analysis, the medical and birth histories of both favorable and adverse obstetric outcomes that occurred in medical organizations of all levels in Perm and the Perm Region in 2007–2018 were used. The comparative analysis included clinical and laboratory characteristics of the examination results and the course of pregnancy, delivery and the postpartum period. The risk of COC was assessed using the Kruskal – Wallis test. The relationship between quantitative variables was determined using the linear correlation coefficient (r). The data were analyzed in the Excel® 2016 spreadsheet processor using the author's [1] Stat2015 package. The LII was assessed (in conventional units – c. u.), according to the Ya.Ya. Kalf-Kalif formula [2] at different stages of pregnancy and in the postpartum period, which allowed us to determine the dynamics of changes depending on the risk group and gestation period.

Results. Early laboratory markers of COC were established (iron deficiency anemia, high levels of LII, elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), urea and creatinine, decreased fibrinogen, prothrombin index (PI) and prolonged thrombin time (TT)).

Conclusions. Reliably significant laboratory markers of the risk for developing COC have been identified.

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Introduction

Critical obstetric conditions (COC) are syndromes, symptoms, and complications that require timely, highly specialized care and intensive measures for women during pregnancy, childbirth, and the 42 days following delivery [1–3]. Severe maternal outcomes are divided into near-miss maternal mortality (NMM) and obstetric death, the main causes of which are extragenital diseases, hemorrhage, preeclampsia and eclampsia, amniotic fluid embolism, clinically narrow pelvis, and unsafe abortion [4]. Near-miss maternal mortality is a critical obstetric condition (COC) close to death experienced by a pregnant woman or woman who has recently given birth, who survived as a result of timely and high-quality highly specialized medical care [3]. The incidence of NMM worldwide reaches 1.4 % of all pregnancies and varies by region.

Systematic analysis of causes and monitoring of COC in Russia can reduce maternal mortality (MM) [5]. Consequently, the priority area for reducing MM in the population is the prediction and timely identification of risk factors and laboratory markers for the development of COC. The relevance of early preclinical prediction of COC is currently high.

The currently accepted methods for assessing the prognosis of obstetric pathology, regulated by Order No. 572n of the Ministry of Health of the Russian Federation dated November 12, 2012, based on the analysis of obstetric-gynecological and somatic medical histories and previous obstetric complications, are imperfect, as their prognostic value remains limited. For example, chronic diseases are recorded in 80 % of pregnant women, infectious and inflammatory processes in 74.6 %, and placental dysfunction and fetal hypoxia in 25–77 % of cases [6–9], while truly life-threatening conditions are detected in only 1.3–2.7 % of births [10].

A complete blood count is part of the standard set of tests during pregnancy, and an increase in white blood cells and changes in the white blood cell count do not always predict obstetric complications. This has sparked interest in the leukocyte intoxication index (LII), calculated using the formula developed by Y.Y. Kalf-Kalifa, which reflects the severity of the systemic inflammatory response and can therefore be used as an early marker of COC, since exceeding the LII level in the first (especially), second, and third trimesters can be considered a risk for the development of COC. A comparative analysis between the groups showed that the LII level for women in the control group in the first trimester was 0.84 ± 0.40 conventional units (95 % CI 0.70–0.99), in the second trimester it was 1.64 ± 1.40 conventional units (95 % CI 1.07–2.21), and in the third trimester it was 1.59 ± 0.96 conventional units (95 % CI 1.15–2.03) [12], while in complicated pregnancies it significantly exceeded 1.5, 2.21, and 2.03 conventional units in the first, second, and third trimesters, respectively [12].

The COC prediction method, based on risk factors (socio-behavioral, general somatic, and obstetric-gynecological) and increased LII in the first and second trimesters of pregnancy [13; 14], allows for the identification of high-risk groups for obstetric complications*. To date, there is no laboratory prediction of adverse maternal outcomes, therefore early laboratory markers of COC are proposed based on complete blood count, biochemical results, and coagulogram.

The aim of the study is to identify early laboratory markers of risk for the development of critical obstetric conditions.

Materials and Methods

The comparative analysis includes medical records and birth histories with favorable and unfavorable outcomes from medical institutions of all levels of care in Perm and the Perm Territory between 2007 and 2018. Depending on the outcome of the pregnancy and the severity of complications, all observations were classified into four groups:

Control group (Group I) – women with a favorable pregnancy course and outcome in childbirth (n = 52).

Group II – patients with complications requiring hospitalization or drug therapy, but who completed their pregnancy without severe maternal and perinatal complications (n = 50).

Group III – women who have experienced severe obstetric complications and survived thanks to emergency and highly skilled medical care (n = 54).

Group IV – cases of death during pregnancy, childbirth, or within 42 days after their completion, accompanied by fetal or infant loss (n = 30).

A retrospective analysis was conducted of clinical and laboratory characteristics, including examination results: the course of pregnancy, childbirth, and the postpartum period in groups with favorable and unfavorable outcomes. The Kruskal–Wallis statistical test was used to assess the significance of differences between groups.

Correlations between quantitative variables were analyzed using Pearson's linear correlation coefficient (r). Statistical data processing was performed in Excel® 2016 using the proprietary software package Stat2015.

To assess LII (in conventional units – conv. units) using the formula developed by Y.Y. Kalf-Kalifa, indicators were determined at various stages of gestation and in the postpartum period, which made it possible to track the dynamics of changes depending on the risk of developing COC and the outcome of pregnancy.

Results and Discussion

The analysis showed that almost all patients in the compared groups were diagnosed with anemia, which increases the risk of maternal and perinatal complications: in group I – in 37 women (71.2 %); in group II – 38 (76.0 %); in group III – 26 (48.1 %); and in group IV – 21 (70.0 %), which is statistically significant (H = 13,341; p <  0,05) (Fig. 1).

 

Fig. 1. Iron deficiency conditions in comparison groups, %

 

Most women in the control group were diagnosed with grade I anemia. In group II, 66.0 % had grade I anemia, 6.0 % had grade II anemia, and 4.0 % had grade III anemia. In group III, 44.0 % of patients were diagnosed with grade I anemia, and 3.7 % had severe anemia. The highest rate of severe anemia was recorded in group IV – 23.3 % (Fig. 2). Pairwise comparisons revealed significant differences between groups III and II (U = 950.0; p = 0.05), III and IV (U = 444.0; p = 0.05), as well as between the control and I groups (U = 548,0; p = 0,05).

The leukocyte intoxication index (LII) remained within normal limits in women with favorable pregnancy outcomes (in the first trimester ≤ 1.5 conventional units; in the second trimester ≤ 2.21; in the third trimester ≤ 2.03). In the group of women with maternal losses, the LII was significantly higher from the first trimester onwards and remained high until delivery and in the postpartum period. In the first trimester, the LII in group IV was 27.05 ± 50.9, in the second trimester – 26.6 ± 44.2, and in the third trimester and postpartum period, significant differences were found between the compared groups (Н = 31,942; p <  0,001).

 

Fig. 2. Iron deficiency conditions by severity in comparison groups, %

 

In the third trimester, the average LII level in deceased women was 6.7 ± 2.9 versus 1.7 ± 0.5 in the control group (t = 3.333; p <  0.005). On days 1–2 after delivery, the LII in deceased women reached 45.6 ± 47.4 compared to 3.9 ± 1.2 in the control group (U = 93.00; p <  0.012), and on days 3–4, it was 154.7 ± 270.5 versus 2.6 ± 0.8, respectively (H = 42.099; p = 0.001; U = 55.00; p <  0.001). On days 5–6, the LII in group III was 6.6 ± 3.0, and in group IV, it was 8.4 ± 2.6 (t = 4.371; p <  0.001), which also confirms the persistence of inflammatory activity (Table 1).

 

Table 1. Level of LII (leukocyte intoxication index) at different stages of pregnancy, childbirth, and the postpartum period in the compared groups, conditional units

Leukocyte intoxication index

Group I, n = 52

Group II, n = 50

Group III, n = 54

Group IV, n = 30

Н- criterion

р-value

First trimester

1.3 ± 0.3

1.7 ± 0.3*

1.4 ± 0.3

27.5 ± 50.9

5.921

0.116

Second trimester

2.0 ± 0.5

2.0 ± 0.4

1.6 ± 0.4****

26.6 ± 44.2

2.782

0.426

Third trimester

1.7 ± 0.5

1.7 ± 0.4 ****

3.0 ± 1.2 ****

6.7 ± 2.9 *

31.942

0.001

Before delivery

2.2 ± 1.0 ***

2.8 ± 0.7

4.5 ± 1.7

–

34.5

0.298

1–2 days after delivery

3.9 ± 1.2

4.7 ± 2.4

6.1 ± 1.2

45.6 ± 47.4 *

7.411

0.060

3–4 days after delivery

2.6 ± 0.8 ***

2.60 ± 0.8 ****

3.9 ± 1.8 ****

154.7 ± 270.5 *

42.099

0.001

5–6 days after delivery

2.4 ± 0.6

–

6.6 ± 3.0 ****

8.4 ± 2.6 *

–

–

Note: here and further in the tables: * – reliable difference in data with group I; ** – with group II; *** – with group III; **** – with group IV; p/p – postpartum period. Normal range: first trimester – 1.51 conventional units; second trimester – 2.21 conventional units; third trimester of pregnancy – 2.03 conventional units.

 

Biochemical blood analysis showed no significant differences between the groups in terms of sugar and bilirubin levels. On the contrary, total protein levels in groups II and IV (66.3 ± 2.0 and 64.2 ± 3.4, respectively) differed significantly from those in the control group (69.0 ± 2.1), differences are significant (groups II and I – U = 953.0; p = 0.029; groups IV and I – U = 204.0; p = 0.003). The AST level was significantly higher in group IV (46.7 ± 27.5) compared to the control group (14.5 ± 2.1; U = 204.0; p = 0.003) and group III (21.2 ± 8.0; U = 191.5; p = 0.034). In group II, the AST level (19.9 ± 4.9) was significantly lower compared to the data for group IV (U = 204.0; p = 0.003).

Renal function indicators (urea and creatinine) were significantly higher in deceased women: for urea (H = 20.209; p < 0.001) and creatinine (H = 10.711; p = 0.013), significant differences were recorded with groups II and III (U = 113.0 and U = 75.0; both p <  0.001). Creatinine was also higher in group II compared to group I (U = 678.0; p = 0.002) (Table 2).

 

Table 2. Biochemical blood parameters during pregnancy in different study, M ± 2m

Indicator

Group I, n = 52

Group II, n = 50

Group III, n = 54

Group IV, n = 30

Н- criterion

р-value

Blood sugar, mmol/L

(normal range: 3–6.1)

4.3 ± 0.2

4.3 ± 0.2

5.4 ± 2.1

4.4 ± 0.7

0.361

0.948

Total protein, g/L

(normal range: 60–85 g/L)

69.0 ± 2.1

66.3 ± 2.0*

67.2 ± 2.2

64.2 ± 3.4*

6.932

0.074

Bilirubin, μmol/L

(normal range: 0–20.5)

11.0 ± 1.1

9.8 ± 0.9

9.6 ± 1.0

14.5 ± 5.6

4.835

0.184

AST, U/l

(normal: 0–32)

14.5 ± 2.1

19.9 ± 4.9 ****

21.2 ± 8.0 ****

46.7 ± 27.5*

10.206

0.017

АLТ, U/L

(норма: 0–31)

16.6 ± 4.3

22.4 ± 11.4

21.5 ± 7.5

50.7 ± 36.6

2.855

0.414

Creatinine, μmol/L

(normal range: 44–97)

36.2 ± 9.5

57.8 ± 6.8*

42.1 ± 11.0

68.6 ± 40.2

10.714

0.013

Urea, mmol/L

(normal range: 1.7–8.3)

3.2 ± 0.4

2.9 ± 0.3 ****

2.9 ± 0.3 ****

5.7 ± 1.5*

20.209

 <  0.001

 

The fibrinogen level in the comparison groups has reliable values (H = 9.178; p = = 0.028). Fibrinogen in group II is significantly higher than in the control group (U = 817.0; p = 0.042) and the group of deceased women (U = 226.0; p = 0.023).

In the group of survivors, the fibrinogen level is significantly lower than in group II (U = 568.0; р = 0.015).

A decrease in the international normalized ratio (INR) was also noted in the comparison groups (H = 9.735; p = 0.021), with the indicator in group II significantly lower than in group IV (t = 2.721; p = 0.010) and the control group (U = 217.5; p = 0.008).

The prothrombin index (PTI) in the compared groups showed a significant difference (H = 42.041; p <  0.001). A decrease in PTI was recorded in the group of deceased women, especially in comparison with the control group (t = 9.240; p <  0.001), and reduced values in the group of deceased women compared to the values in group II (t = 7.767; p <  0.001). Significance was determined between groups II and IV (U = 20.0; p <  0.001) and between the control group and group III (t = 11.312; p <  0,001).

In the group of women with maternal losses, thrombin time (TT) was prolonged (21.0 ± 13.4) compared to data from groups II (U = 54.0; p = 0.007) and IV (t = 3.510; p = 0.002). In group II, thrombin time was shorter compared to the control group (t = 3.573; p = 0.001) (Table 3).

 

Table 3. Hemostasis system indicators in women from different study groups, M ± 2m

Indicator

Group I, n = 52

Group II, n = 50

Group III, n = 54

Group IV, n = 30

Н- criterion

р-value

Fibrinogen, g/L

(normal range: 2–4)

4.7 ± 1.3

4.8 ± 0.4*. ****

4.0 ± 0.4**

3.9 ± 0.4

9.178

0.028

INR (international normalized ratio)

2.1 ± 2.1

1.0 ± 0.0 *.****

1.0 ± 0.0

1.1 ± 0.2

9.735

0.021

PTT, with

(norm: 24,3–35)

27.5 ± 1.2

28.7 ± 1.6

29.3 ± 1.6

26.6 ± 5.9

2.500

0.475

PTI

(norm: 80–110)

1.0 ± 0.0***

11.7 ± 11.8 ****

88.6 ± 15.2 **

88.0 ± 18.4*

42.041

 <  0.001

PTT, with

(norm is up to 11 per minute)

13.8 ± 1.1

14.1 ± 0.6

14.1 ± 0.6

17.2 ± 3.9

3.667

0.300

TT, with

(norm 11–17.8 s)

14.9 ± 1.3

11.9 ± 1.2 *.****

21.0 ± 13.4**

15.9 ± 1.3

15.900

 <  0.001

Fibrin monomers soluble complex, unit

(norm 0–3.5)

6.2 ± 2.0

5.8 ± 0.9

4.6 ± 1.3

–

4.140

0.247

D-dimer, ng/mL (norm 0–1680)

521.0 ± 357.9***

587.4 ± 78.0

4530.5 ± 5355.8**

–

9.099

0.028

 

The study results showed a high level of moderate anemia among patients from socially vulnerable groups (SVG), which can be explained by social and behavioral factors.

The data obtained confirm the important role of LII as a predictor of complications: already in the first trimester, it exceeded the norm in women with unfavorable outcomes, and after childbirth, it increased tenfold. This reflects the development of a toxic-inflammatory process, indicating decompensation of homeostasis systems.

Signs of multiple organ failure have been identified in women with severe outcomes: increased AST, ALT, urea, and creatinine, which may serve as early biochemical markers of adverse pregnancy outcomes. Hemostasis disorders (decreased fibrinogen and PTI, prolonged TT) can be regarded as early manifestations of DIC syndrome before the development of clinically significant critical obstetric conditions.

Conclusions

  1. Early laboratory markers associated with the risk of developing critical obstetric conditions (COC) include: iron deficiency anemia, especially severe anemia, common among women from high social risk groups; an increase in the leukocyte intoxication index (LII) as early as the first trimester of pregnancy, with an increase during pregnancy and in the postpartum period, reflecting a systemic inflammatory response and decompensation of adaptive mechanisms; biochemical signs of incipient multiple organ failure – increased levels of AST, ALT, urea, and creatinine with a decrease in total protein; hemostasis system disorders: decreased fibrinogen, prothrombin index (PTI), prolonged thrombin time (TT), which can be regarded as initial manifestations of developing DIC syndrome.
  2. The laboratory profile of a pregnant woman at high risk of COC can be established long before the clinical manifestation of severe complications, which emphasizes the diagnostic significance of a comprehensive assessment of standard indicators of general, biochemical, and coagulation analyses.
  3. Timely interpretation of laboratory data in dynamics can significantly improve the accuracy of early prediction of adverse pregnancy outcomes and justify the need for: interdisciplinary consultation; hospitalization in a specialized hospital (level III); early initiation of therapy aimed at correcting pathological processes.

 

* V.V. Skryabina, M.M. Padrul, S.N. Berseneva, I.V. Kondratyuk. Method for predicting the development of critical conditions in women during childbirth and the postpartum period. No. 2647459 C1 Russian Federation. IPC G01N 33/48; M.M. Padrul, N.V. Isaeva, E.V. Cherkasova, S.N. Berseneva. Method for predicting the risk of adverse maternal outcomes during pregnancy, childbirth, and the postpartum period. No. 2803129 C1 Russian Federation. IPC G01N 33/48.

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About the authors

M. M. Padrul

Ye.A.. Vagner Perm State Medical University

Author for correspondence.
Email: bers.s2014@yandex.ru
ORCID iD: 0000-0002-6111-5093

DSc (Medicine), Professor, Head of the Department of Obstetrics and Gynecology

Russian Federation, Perm

N. V. Isaeva

Ye.A.. Vagner Perm State Medical University

Email: bers.s2014@yandex.ru
ORCID iD: 0009-0007-0626-7979

DSc (Medicine), Professor, Vice-Rector for Continuous Professional Development, Head of the Department of Public Health and Healthcare with a Course in Law

Russian Federation, Perm

S. N. Berseneva

Perm Regional Clinical Hospital

Email: bers.s2014@yandex.ru
ORCID iD: 0009-0003-1668-6748

PhD (Medicine), Obstetrician-gynecologist

Russian Federation, Perm

E. V. Cherkasova

Medical Information Analytical Center

Email: bers.s2014@yandex.ru
ORCID iD: 0009-0001-4696-3545

DSc (Medicine), Methodologist

Russian Federation, Perm

A. A. Gorokhova

Women's Health Clinic, Perm

Email: bers.s2014@yandex.ru
ORCID iD: 0009-0006-6062-8854

Obstetrician-gynecologist

Russian Federation, Perm

References

  1. Шелудько В.С., Девяткова Г.И. Теоретические основы медицинской статистики (статистические методы обработки и анализа материалов научно-исследова¬тельских работ: учеб.-метод. пособие. 3-е изд., исправл. и доп. Пермь; Саратов: Амирит 2019; 96. / Sheludko V.S., Devyatkova G.I. Theoretical foundations of medical statistics (statistical methods of processing and analysis of research materials: textbook.-method. manual. 3rd ed., corrected. and additional. Perm; Saratov: Amirit 2019; 96 (in Russian).
  2. Кальф-Калиф Я.Я. О лейкоцитарном индексе интоксикации и его практическом значении. Врачебное дело 1941; 1: 31–35. / Kalf-Kalif Ya.Ya. On the leukocyte index of intoxication and its practical significance. Medical Business 1941; 1: 31–35 (in Russian).
  3. Пырегов А.В., Шмаков Р.Г., Фёдорова Т.А., Юрова М.В. и др. Критические состояния «near miss» в акушерстве: трудности диагностики и терапии. Акушерство и гинекология 2020; 3: 228–237. / Pyregov A.V., Shmakov R.G., Fedorova T.A., Yurova M.V. et al. Critical conditions of "near miss" in obstetrics: difficulties of diagnosis and therapy. Obstetrics and Gynecology 2020; 3: 228–237 (in Russian).
  4. Зиганшин А.М., Нагимова Э.М., Мараканов Р.М., Мудров В.А. Материнская смертность: структура и пути решения проблемы. Журнал акушерства и женских болезней 2021; 70 (5): 5–14. / Ziganshin A.M., Nagimova E.M., Marakanov R.M., Mudrov V.A. Maternal mortality: structure and ways of solving the problem. Journal of Obstetrics and Women's Diseases 2021; 70 (5): 5–14 (in Russian).
  5. Мурашко М.А., Сухих Г.Т., Пугачев П.С., Филиппов О.С. и др. Международный и российский опыт мониторирования критических акушерских состояний. Акушерство и гинекология 2021; 3: 5–11. / Murashko M.A., Sukhoi G.T., Pugachev P.S., Filippov O.S. et al. International and Russian experience in monitoring critical obstetric conditions. Obstetrics and Gynecology 2021; 3: 5–11 (in Russian).
  6. Шехтман М.М. Руководство по экстрагенитальной патологии у беременных. Издание третье. М.: Триада 2005; 816. / Shekhtman M.M. Guidelines on extragenital pathology in pregnant women. Third edition. Moscow: Triad 2005; 816 (in Russian).
  7. Стрижак Н.В., Егорова А.Т., Моисеенко Д.А. Социальный статус и соматическая патология беременных женщин с пороками сердца. РМЖ. Мать и дитя 2016; 5: 334–335. / Strizhak N.V., Egorova A.T., Moiseenko D.A. Social status and somatic pathology of pregnant women with heart defects. Russian Journal of Woman and Child Health 2016; 5: 334–335 (in Russian).
  8. Сидельникова В.М. Подготовка и ведение беременности у женщин с привычным невынашиванием: метод. пособия и клин. протоколы. 3-е изд. М.: МЕДпресс-информ 2013; 224. / Sidelnikova V.M. Preparation and management of pregnancy in women with habitual miscarriage: method. benefits and wedge. protocols. 3rd ed. Moscow: MEDpress-inform 2013; 224 (in Russian).
  9. Акушерство. Национальное руководство. Под ред. Г.М. Савельевой, Г.Т. Сухих, В.Н. Серова, В.Е. Радзинского. М.: ГЭОТАР-Медиа 2015; 1088. / Obstetrics. National leadership. Edited by G.M. Savelyeva, G.T. Sukhoi, V.N. Serov, V.E. Radzinsky. Moscow: GEOTAR-Media 2015; 1088 (in Russian).
  10. Кукарская И.И. Эффективность мониторинга критических акушерских больных в Тюменской области. Образовательный конгресс «Современные технологии охраны материнства и детства в Западной Сибири». Тюмень 2014. / Kukarskaya I.I. The effectiveness of monitoring critical obstetric patients in the Tyumen region. Educational Congress "Modern technologies for the protection of motherhood and childhood in Western Siberia". Tyumen 2014 (in Russian).
  11. Bone R.C., Balk R.A., Cerra F.B. et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine (англ.). Chest 1992; 6 (101): 1644–1655.
  12. Скрябина В.В. Показатели лейкоцитарного индекса интоксикации у беременных при физиологическом и осложненном течении гестации. Приволжский научный вестник 2012; 7 (11): 49–54. / Scriabina V.V. Indicators of leukocyte intoxication index in pregnant women with physiological and complicated course of gestation. Privolzhsky Scientific Bulletin 2012; 7 (11): 49–54 (in Russian).
  13. Падруль М.М., Исаева Н.В., Черкасова Е.В., Берсенева С.Н. Факторы риска материнской и несостоявшейся материнской смертности, прогнозирование тяжелых акушерских состояний. Пермский медицинский журнал 2022; 39 (6): 97–105. / Padrul M.M., Isaeva N.V., Cherkasova E.V., Berseneva S.N. Risk factors of maternal and failed maternal mortality, prognosis of severe obstetric conditions. Perm Medical Journal 2022; 39 (6): 97–105 (in Russian).
  14. Падруль М.М., Исаева Н.В., Черкасова Е.В., Берсенева С.Н Особенности анамнеза, результатов и обследования, течения беременности, родов и послеродового периода у женщин с несостоявшейся материнской смертностью. Научный форум: медицина, биология и химия: материалы XV Международной научно-практической конференции. М.: Изд. МЦНО 2018; 7 (15):15–26. / Padrul M.M., Isaeva N.V., Cherkasova E.V., Berseneva S. Features of anamnesis, results and studies, the course of pregnancy, childbirth and the postpartum period in a woman with failed maternal mortality. Scientific forum: Medicine, Biology and chemistry: proceedings of the XV International Scientific and practical conference. Moscow: Ed. MCN, 2018; 7 (15): 15–26 (in Russian).

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