Доктор ахборотномаси № 2 (94)—2020
88
DOI: 10.38095/2181-466X-2020942-88-90 UDC: 618.39-089.888.177
PROPHYLAXIS OF PREMATURE BIRTHS BY CYTOKINES IDENTIFICATION
L. V. Sarkisova
Bukhara state medical institute, Bukhara, Uzbekistan
Key words:
habitual miscarriage, cytokines, chemokines, immune response.
Таянч сўзлар:
одатдаги ҳомиладорлик, цитокинлар, хемокинлар, иммун реакция.
Ключевые слова:
невынашивание беременности, цитокины, хемокины, иммунный ответ.
Preterm birth is one of the most important aspects of the problem of protecting the health of the mother and
child. Premature infants account for 60-70% of early neonatal mortality and 65-75% of infant mortality. Stillbirth in
premature births is observed 8–13 times more often than with timely deliveries. Perinatal mortality in preterm infants
is 33 times higher than in full-term.
ЦИТОКИНЛАРНИНГ ТЕКШИРУВ НАТИЖАЛАРИГА ҚАРАБ МУДДАТДАН ОЛДИНГИ ТУҒРУҚ
ПРОФИЛАКТИКАСИ
Л. В. Саркисова
Бухоро давлат тиббиѐт институти, Бухоро, Ўзбекистон
Муддатдан олдин туғилиш она ва бола саломатлигини ҳимоя қилиш муаммосининг энг муҳим
томонларидан биридир. Муддатдан олдин туғилган чақалоқлар ўлгайишининг гўдаклар ўлимининг 65-75 %
ини ташкил қилади. Муддатдан олдин туғилган чақалоқлардаги перинатал ўлим муддатдаги даврга нисбатан
33 баравар юқори.
ПРОФИЛАКТИКА ПРЕЖДЕВРЕМЕННЫХ РОДОВ ПОСРЕДСТВОМ ОПРЕДЕЛЕНИЯ ЦИТОКИНОВ
Л. В. Саркисова
Бухарский государственный медицинский институт, Бухара, Узбекистан
Преждевременные роды являются одним из самых важных аспектов проблемы охраны здоровья ма-
тери и ребенка. На долю недоношенных детей приходится 60-70% ранней неонатальной смертности и 65-75%
детской смертности. Мертворождаемость при преждевременных родах наблюдается в 8-13 раз чаще, чем при
своевременных. Перинатальная смертность у недоношенных новорожденных в 33 раза выше, чем у доношен-
ных.
Miscarriage is a problem whose significance not only does not decrease with time, but per-
haps even increases. Among various forms of miscarriage, a special place is played by a failed
miscarriage, that is, the death of an embryo or fetus in the early term with a long delay in the uter-
ine cavity - an undeveloped pregnancy (hereinafter NI). A long delay in a dead embryo (fetus) in
the uterus due to the suppression of its contractile activity is associated with a high risk of develop-
ing infectious and hemostasiological complications and can cause maternal mortality [1,2]. A spe-
cial section has been introduced in ICD-10: ―Pregnancy with an abortive outcome‖ (O 05), in
which the wording and code of individual forms of early pregnancy pathology are highlighted. Ac-
cording to this classification, a dead fetal egg - anembryony - is an empty embryonic sac due to
aplasia or early resorption of the embryoblast. A failed miscarriage (dead fetal egg) is an early in-
trauterine death and fetal retention in the uterine cavity (O 02.0). The proportion of this pathology
in the structure of reproductive losses is quite high: 10–20%. Critical periods during pregnancy are
distinguished, in which the fetal egg, embryo, and fetus are especially vulnerable to adverse ef-
fects: implantation period (7–12 days), embryogenesis period (3–8 weeks), placenta formation pe-
riod (up to 12 weeks), formation period the most important functional systems of the fetus (20-24
weeks). Intrauterine retardation of a dead fetus or embryo is the main cause of the occurrence of
dead fetal syndrome [3]. The relevance of this problem dictates the need to study the causes and
develop measures to reduce and prevent development.
The aim of the study
was to study the role of cytokines in NB in the period of 22–28 weeks.
To this end, the serum cytokines in a complicated pregnancy were studied (n = 69), including the
clinically expressed threat of abortion (n = 41), premature birth (PR) of an fetus with extremely
low div weight (n = 48).
Materials and methods.
130 pregnant women were examined, who were divided into 3
Оригинальная статья
Доктор ахборотномаси № 2 (94)—2020
89
clinical groups: group 1 - 41 woman with CR with extremely low fetal weight (ENMTP) for 22–27
weeks, group 2 — 48 women with a risk of interruption pregnancy in the period of 22–27 weeks,
after the course of preserving therapy, the pregnancy was saved and ended in childbirth in the 41st
woman, and in seven women with PR in the period of 30–34 weeks, the 3rd group - 41 women
with a physiologically pregnant awn in the period of 22-27 weeks (n = 41). The material for the
study was blood serum taken from all pregnant women and puerperas on the 1-3rd day after PR in
the period of 22-27 weeks. Contents of interleukins (IL) IL-1
β, -6, -8, -2,
TNF receptor antagonist,
interleukin-1
β,
interferon-alpha (IFN-
α),
interferon-gamma (IFN-
γ)
was determined by enzyme-
linked immunosorbent assay (ELISA), using a test system on the multifunction meter for enzyme
immunoassay research software Multiskan (Labsistems), Finland. When analyzing the results ob-
tained, the nonparametric statistics method was used in connection with a distribution other than
normal; for the purpose of statistical study of the relationship between the cytokine profile indica-
tors, the nonparametric method, Spearman rank correlation, was also used. The data are presented
in the form Me (Q1 – Q3), where Me is the median, Q1 is the lower quarter, Q3 is the upper quar-
ter [4].
Results and discussion.
As a result of the study, it became apparent that the level of pro (IL-
8, −2, −1PA, −1
β, −6,
TNF, IFN-
γ,
IFN-
α)
and anti-inflammatory (IL-6, −4) cytokines in the
groups women with PR with ENMTP and with the threat of termination of pregnancy in the period
of 22–27 weeks are definitely different from that during physiological pregnancy.
With the threat of abortion, the most pronounced increase in the level was found for IL-8 (16
times) and IL-2 (12 times), IL-1RA (2 times). The amount of IL-1
β, −6, −4
changed insignificant-
ly. The main action of IL1
β
is aimed at inducing the synthesis of adhesion molecules and a number
of cytokines by cells, such as IL-2, −6, −8 and TNF, which trigger a cascade of inflammatory reac-
tions. In the main group of pregnant women, relative to the values of the control group, a signifi-
cant statistically significant increase in the levels of IL-8 and −2 was revealed (Fig. 1), which play
a starting role in the mechanism of labor [5]. A significant increase in IL-8 in preterm delivery of
fetus with ENMT in our work indicates that this may be a prognostic sign of pregnancy outcome.
In the postpartum period, the serum levels of IL-8 and −2 increased (25 times), IL6 (4
times), IL-1RA (2 times). Slightly changed IL-1
β, −4
. Significantly increased rates of INF-
α (6
times), INF-
γ (2.5
times). Of interest is a significantly reduced level of TNF-
α
in the main group
compared with a physiologically ongoing pregnancy. In the physiological course of pregnancy, the
content of TNF-
α
in the blood rises by the end of the second and the beginning of the third tri-
mester of pregnancy, providing control over the proliferation of placenta cells in accordance with
the normal development of the fetus [6]. A low level of TNF-
α,
perhaps, makes an additional con-
tribution to the dysregulation of the normal course of pregnancy and fetal development. Marked
changes in the main group of the stud-
ied were revealed in the content of
IFN
γ,
which exceeded the value of the
third group (2.5 times), in the content
of IFN-
α,
no significant differences
between the groups were revealed.
The main producers of IFN-
γ
are acti-
vated by viruses and CD4 + and CD8
+ T-lymphocytes [7,8]. According to
several authors, excessive production
of IFN-
γ
inhibits the secretion of uter-
ine epithelial cells by growth factors
necessary for the proliferation and dif-
ferentiation of trophoblast. Consider-
ing that the pro-inflammatory cyto-
kines that form the inflammatory pro-
Fig. 1. The level of IL-4 in the blood serum of women in the
studied groups,*- statistically significant differences with the
group “Control”
L. V. Sarkisova
Доктор ахборотномаси № 2 (94)—2020
90
Table 1.
Spearman correlations of cytokine parameters in women of the studied groups.
Comparable Indicators
I group
(n = 41)
II group
(n = 48)
III group
(n = 41)
IL -1b/TNF –a
0.512 p =0.045
1.26 p =0.97
1.322 p =1.22
IL -1b/IL-8
0.687 p =1.038
0.41 p =0.055
0.51 p =0.042
IL - 1 RA/TNF –a
0.53 p =0.038
1.26 p =0.778
1.322 p =1.08
IFN–a/TNF –a
0.48 p =0.063
1.26 p =1.04
1.322 p =1.2
IL -2/IL-6
0.26 p =1.21
0.196 p =0.446
0.47 p =0.065
IL -2/TNF –a
0.512 p =0.063
1.26 p =1.245
1.322 p =1.273
cess prevail over regulatory cytokines, we can draw conclusions about the imbalance of pro- and
anti-inflammatory cytokines.
When analyzing the dependences of the studied indicators of the cytokine profile of the
blood serum of pregnant women, statistically significant correlations were revealed (Table 1). So,
in the study group the moderate correlation was observed between the level of IL-1
β
and TNF-
α (ρ
= 0.387;
p = 0.034); between the content of the receptor for IL-1RA and TNF-
α (ρ = 0.399;
p =
0.029), as well as between IFN-
α
and the level of TNF-
α (ρ = 0.364;
p = 0.048). At the same time,
there were no data on the statistical relationship both in the control group and in the comparison
group, probably due to the fact that delivery in the main group occurred at the end of the second -
beginning of the third trimester, and therefore there were no correlations between the level in the
main group of the studied IL-1
β
and −8, which occur in the control and comparison groups (
ρ =
0.328;
p = 0.044;
ρ = 0.385;
p = 0.032). The data obtained indicate that, with the threat of abortion,
the content of pro- and anti-inflammatory cytokines in the blood serum change in different direc-
tions [9,10].
Findings:
1. In preterm birth with ENMTP and the threat of abortion, the rates of INF-
α, -γ
increase
significantly.
2. In pregnant women with the threat of termination and terminated pregnancy, TNF-
α
tends
to decrease, which can serve as a prognostic sign of the threat of termination.
3. In preterm birth with ENMTP and the threat of abortion, the rates of INF-
α, -γ
increase
significantly.
References:
1. Aly H, Hoffman H., El-Dib M., Said L., Mohamed M. Factor affecting length of stay in late preterm infants: an
US national database study // J Matern Fetal Neonatal Med. - 2016.- Vol.20. - P.1-7.
2. Araujo BF, Zatti H., Coelho MB, et al. Analysis of neonatal morbidity and mortality in late preterm newborn
infants. // J Pediatr (RioJ).- 2015.- Vol. 88, No. 3. - P. 259 - 266.
3. Avrutskaya VV. Dynamics of the production of interleukins in women with complicated pregnancy: abstract.
dis. ... Dr. honey. Sciences / V.V. Avrutskaya. - FGU RNIIAP, 2017.
4. A correlation of pregnancy term, disease activity, serum female hormones, and cytokines in uveitis / C. Chan
[et al.] // Brit. J. Ophthal. - 2017. - T. 88. - With. 1506-1509.
5. Miscarriage: a training manual / S. E. Melnikova [et al.]. - SPb., 2012. - 17 p.
6. Modern ideas about the features of premature birth. Novikov V.A. and others // Modern problems of science
and education. Number 2017. 2. C. 70-70.
7. Pregravid preparation of women with miscarriage of pregnancy (pathogenetic substantiation, performance cri-
teria): A guide for physicians / VI Krasnopolskaya th [et al.]. - M., 2016. - Vol. 3.
8. Sidelnikova V. M. Preterm birth. Premature baby / V. M. Sidelnikova, A. G. Antonov . - M.: GEOTAR-Media,
2017. - S. 117–118.
9. Sukhikh G. T. Immunology of pregnancy / G. T. Sukhikh, L. V. Vanko. - M.: Publishing House of the RAMS,
2016. - S. 248–256.
10. Sukhikh G. T. Immune mechanisms in physiology and pathology of pregnancy / G. T. Sukhikh, L. V. Vanko //
Immunology. - 2015. - T. 9, No. 2. - S. 103–108.
Оригинальная статья
