Authors

  • Khudoyarova D.R.
    Prof. DSc, Samarkand state medical university, Samarkand, Uzbekistan
  • Shodiklova G.Z
    Prof. DSc, Samarkand state medical university, Samarkand, Uzbekistan
  • Yunusova Z.M.
    Samarkand state medical university, Samarkand, Uzbekistan

DOI:

https://doi.org/10.37547/ajsshr/Volume04Issue02-04

Keywords:

Undifferentiated connective tissue dysplasia (uCTD) tumor necrosis factor (TNF-) connective tissue (CT)

Abstract

The main function of CT is to provide structural support to other tissues. Cartilage and bone are the main types of connective tissue, other types include areolar connective tissue, which holds organs together, and dense connective tissue, which forms ligaments and tendons. We examined 47 pregnant women with uCDT and 15 healthy pregnant women without uCDT aged 24-30 years. The threat of termination of pregnancy occurred in 50% of women with uCDT, and the threat of preterm birth was observed 6 times more often than in healthy pregnant women. Thus, pregnant women with signs of various forms of uCDT belong to high-risk groups of obstetric and perinatal pathology, and therefore they need close monitoring during pregnancy, childbirth and the postpartum period, and it is also necessary to examine newborns who have a high probability of inheriting this disease.             


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ABSTRACT

The main function of CT is to provide structural support to other tissues. Cartilage and bone are the main types of

connective tissue, other types include areolar connective tissue, which holds organs together, and dense connective

tissue, which forms ligaments and tendons. We examined 47 pregnant women with uCDT and 15 healthy pregnant

women without uCDT aged 24-30 years. The threat of termination of pregnancy occurred in 50% of women with uCDT,

and the threat of preterm birth was observed 6 times more often than in healthy pregnant women. Thus, pregnant

women with signs of various forms of uCDT belong to high-risk groups of obstetric and perinatal pathology, and

therefore they need close monitoring during pregnancy, childbirth and the postpartum period, and it is also necessary

to examine newborns who have a high probability of inheriting this disease.

KEYWORDS

Undifferentiated connective tissue dysplasia (uCTD), tumor necrosis factor (TNF-), connective tissue (CT), interleukin-

1 (IL-1).

Research Article

DEBATABLE ISSUES OF PATHOLOGICAL COURSE OF PREGNANCY AND
CHILDBIRTH IN CONNECTIVE TISSUE DYSPLASIA

Submission Date:

January 31, 2024,

Accepted Date:

February 05, 2024,

Published Date:

February 10, 2024

Crossref doi:

https://doi.org/10.37547/ajsshr/Volume04Issue02-04


Khudoyarova D.R.

Prof. DSc, Samarkand state medical university, Samarkand, Uzbekistan

Shodiklova G.Z

Prof. DSc, Samarkand state medical university, Samarkand, Uzbekistan


Yunusova Z.M.

Samarkand state medical university, Samarkand, Uzbekistan

Journal

Website:

https://theusajournals.
com/index.php/ajsshr

Copyright:

Original

content from this work
may be used under the
terms of the creative
commons

attributes

4.0 licence.


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INTRODUCTION

The main function of CT is to provide structural support

to other tissues. Cartilage and bone are the main types

of connective tissue, other types include areolar

connective tissue, which holds organs together, and

dense connective tissue, which forms ligaments and

tendons. Undifferentiated connective tissue dysplasia

(uCTD) is a heterogeneous group of diseases that, in

turn, can lead to various chronic diseases. uCDT often

corresponds to abnormal structural and functional

changes in CT. This leads to disturbances in the

morphology and function of organs [11]. The clinical

and morphological manifestations of uCDT are

extremely diverse. They may include skeletal changes

associated with cartilage disorders, disproportionately

long limbs, arachnodactyly, chest deformities, spinal

scoliosis, flat feet, pathology of tooth development,

occlusion, cysts, joint pathology (tendency to

dislocation), hyperelasticity, thinning, a tendency to

traumatize the skin, varicose veins and external signs

of accelerated aging - early formation of wrinkles,

deformation of the oval of the face, including

gravitational ptosis (sagging soft tissues of the face)

[8,9]. Lesions of the cardiovascular system are very

diverse: mitral valve prolapse (the most common of all

cardiac anomalies in CTD is usually detected by

echocardiography), venous insufficiency, varicose

veins, and hemostasis pathologies [7].

Diagnosis of uCDT is based on these symptoms and

additional findings (e.g., anthropometry, external

respiration, reduced heart size, decreased blood

pressure, plethysmography, specific characteristics of

ECG and ultrasound phleboscanning) [10]. According

to the analysis of these phenotypic markers of uCDT,

its prevalence may be relatively high in the general

population (e.g., 8.5% in a sample of 400 people [9]).

Although it is often stated that the etiology of DST has

a genetic component, an exhaustive analysis of the

relative roles of environmental factors (nutrition,

environmental conditions, movement hygiene, psycho-

emotional background) and genetic factors has not

been carried out. The term "dysplasia" refers to the

abnormal growth/development of a tissue or organ.

The diagnosis of CDT is made based on a thorough

analysis of symptoms and the results of clinical trials.

However, the diagnosis of DST in practice is rarely

accompanied

by

any

specific

histological

confirmations. Accordingly, dysplasia detected at the

clinical level may correspond to numerous changes in

tissue structure.

In the case of connective tissue, dysplasia (i.e.,

"abnormal growth") can occur due to: 1) abnormal

collagen synthesis or assembly; 2) synthesis of

abnormal collagen; 3) excessive collagen degradation;

4) disorders of the structure of collagen fibers due to

insufficient cross-linking; 5) similar anomalies related


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to elastin fibers; 6) tissue destruction through

autoimmune reactions [5,7]. According to Y. Chia,

mitral valve prolapses accounts for 60.8% of congenital

heart diseases in pregnant women [3]. Clinical

polymorphism of mitral valve prolapse is often

combined with other signs of connective tissue

dysplasia: asthenic physique, pathological joint

mobility, myopia, flat feet, as well as prolapse of other

heart valves, patent foramen ovale, nephroptosis,

biliary dyskinesia, varicose veins, and increased

bleeding. It is known that in patients with mitral valve

prolapse, additional pathways are found 3 times more

often than in the general population [2].

Most often, mitral valve prolapse is asymptomatic, has

a favorable prognosis, but is sometimes associated

with

cardiac

arrhythmias,

heart

failure,

thromboembolism, infective endocarditis, and sudden

death. The peculiarities of the hemodynamics of the

gestational period, namely an increase in the volume of

circulating blood, cardiac output, increase the load on

the cardiovascular system and can provoke the

development of these complications. In some cases, it

is during pregnancy that signs of heart failure and

paroxysmal cardiac arrhythmias manifest themselves

in women with mitral valve prolapse [6]. The greatest

threat is posed by patients with hemodynamically

significant mitral regurgitation and myxomatous

degeneration of the valve leaflets, which are the

source of blood clots and the cause of thromboembolic

complications [12].

In recent years, the problem of the course of

pregnancy and childbirth in women with uCDT, which

is a genetically determined disorder of its development

in the embryonic and postnatal periods, has been

actively discussed. As a result of various mutations in

the genes encoding the structure of collagen and

elastin, defects in fibrous structures and the main

substance of uCDT are formed, followed by the

development of various morphofunctional disorders of

a systemic and local nature [6].

The morphological basis of uCDT is a decrease in the

content of certain types of collagen or a violation of the

ratio between them, which leads to a decrease in the

strength of the connective tissue of many organs and

systems. The external manifestation of uCDT is the so-

called "dysembryogenesis stigmas", which can

manifest themselves as both obvious deformities and

subtle signs. Up to 35% of healthy people have some

degree of uCDT, and 70% of them are women [3]. The

variety of mutagenic effects on the development of

this pathology determines a wide range of its clinical

variants - from well-known gene differentiated

syndromes (Marfan, Ehlers-Danlos) - to numerous

hereditary undifferentiated (nonsyndromic) uCDT.

uCDTs are thought to be "phenotypic" copies of known

syndromes [8]. The generalized nature of connective

tissue damage affects the pathological development


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of the organs of the reproductive system, which

further provokes the manifestation of a number of

obstetric problems [12]. In contrast to syndromic

forms, uCDT is manifested mainly by mild

heterogeneous symptoms and syndromes, united

under the general name of "dysembryogenesis

stigmas" [1,3]. The peculiarities of the course of

pregnancy and childbirth in women with uCDT have

not been sufficiently studied and are the subject of

close attention of researchers. Pregnancy pathology

occurs significantly more often in women with uCDT

than in healthy women - 85.5% versus 53.3%, there are

indications in the literature of a higher incidence of the

threat of early and late termination of pregnancy in

women with uCDT. There is also a higher incidence of

preeclampsia and eclampsia in women with uCDT [7,8].

METHODS

Methods of investigation: We examined 47 pregnant

women with uCDT and 15 healthy pregnant women

without uCDT aged 24-30 years. The threat of

termination of pregnancy occurred in 50% of women

with uCDT, and the threat of preterm birth was

observed 6 times more often than in healthy pregnant

women. The main cause of recurrent miscarriage in this

group of patients was isthmic-cervical insufficiency. At

the same time, according to our data, the threat of

termination of pregnancy at a period of up to 20 weeks

occurred in almost 1/3 of cases, the threat of premature

birth - in 17.2%, pregnancy ended in premature birth in

4.6% of cases. Analysis of the course of the gestational

process in pregnant women with uCDT revealed that

one of the most common complications was early

gestosis, which occurred in 48.6% of cases. At the same

time, there was a direct significant correlation

between the severity of the clinical picture and the

incidence of early gestosis. According to our data, the

most common complication of the second half of

pregnancy in women with uCDT was preeclampsia

(49.8%), and the course of childbirth in these patients

was characterized by frequent complications. It is

known that preeclampsia occupies the 2nd-3rd place in

the structure of causes of maternal mortality and is one

of the main causes of premature birth and perinatal

fetal death. One in five children born to a mother with

preeclampsia has some degree of abnormality in

physical and psycho-emotional development. Also,

placental dysfunction was very common in uCDT - in

37.5% of cases. At the same time, there was a violation

of uteroplacental and fetal hemodynamics, transport,

trophic, endocrine, metabolic functions of the

placenta, which led to fetal malformations (12.1%).

However, this assumption cannot be considered

indisputable. The main clinical manifestation of

placental dysfunction in pregnant women with uCDT

was fetal distress. Microscopy of the placenta in

puerperas with uCDT showed various forms of

impaired placental maturation. Another, no less

important complication for obstetrics - untimely


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discharge of amniotic fluid - was observed in 40.0% of

cases in women with uCDT. The incidence of premature

and early rupture of amniotic fluid in our pregnant

women with uCDT ranged from 37.4% to 41.7% of cases.

The microscopic picture of fetal membranes in uCDT

was characterized by thickening of the compact layer

of the amnion of varying degrees of severity due to the

proliferation of collagen fibers in it. Of the features of

the course of labor associated with uCDT, a

relationship with a rapid and rapid course of labor was

revealed, and in severe cases of uCDT, the frequency of

rapid and rapid labor in primiparous women reached

47%, and in mild signs of uCDT was about 14%. Recently,

a new concept of the development of labor weakness

(DLW) has been put forward, in which its causal factor

may belong to the uCDT. The data of the literature

review indicate a fairly high incidence of ECS, which is

2-10% in parturient women with its primary

development and 2.5% in its secondary development. In

women over 30 years of age, ECS is 2 times more

common than in women aged 20-25 years. ECS leads to

a protracted course or complete cessation of labor, the

appearance of signs of fetal distress, which leads to

prompt delivery. In the structure of emergency

caesarean section, ECS ranks 2-3rd, reaching 37% [9,10].

It is known that during pregnancy there are significant

changes in the structure of muscle tissue and collagen

fibers of the cervix. The volume of muscle tissue

increases by more than 2 times due to the growth of

the vascular link with the simultaneous destruction of

collagen fibers. In the course of many studies, it was

found that in 15-20% of women such changes were not

observed, which made it possible to attribute such

patients to the risk group for the development of

abnormalities in labor [14]. Another discussed cause of

DRD is the pathology of immune status. As is known,

endogenous prostaglandins and endothelial growth

factors play an important role in the nature of labor

[13]. It has been established that the main role in the

development of labor belongs to the fetus. At the

junction of maternal and fetal tissues in the uterus,

there is a release of the main modulators of myometrial

contractile activity - prostaglandins of fetal and

maternal origin. As a result, another mechanism of

childbirth is triggered - immunological rejection of the

fetus [10]. Cytokines such as interleukin-1 (IL-1), IL-6, IL-

8 and tumor necrosis factor (TNF-) are of great

importance in the mechanism of labor [11]. The study

of the peculiarities of the course of pregnancy and

childbirth in 47 patients with small and large signs of

uCDT made it possible to establish that abnormalities

of labor in the first stage of labor occurred in 75.3% of

parturient women against 23.7% in the control group

without uCDT. Caesarean section in the study group

was performed in 15% of pregnant women and only in

3% of patients in the control group. Hypotonic bleeding

in the third stage of labor occurred in 7.8% of mothers

with uCDT and was absent in the control group. Pubic

joint divergence was diagnosed in 8.3% of women with

uCDT and was not detected in the control group. Signs


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of prolapse of the internal genitals, confirmed by

clinical and ultrasound data, were found in 45% of

patients in the main group, in the control group this

pathology was not revealed. Birth injuries of newborns

from mothers with uCDT were diagnosed in 38% of

cases versus 3.9% in the control group. This study

showed that patients with generalized manifestations

(involvement of three or more organs in the

connective tissue defect) of uCDT, even in the absence

of severe forms of this pathology, are at high risk for

the formation of obstetric and neonatal pathology [4].

CONCLUSION

Thus, pregnant women with signs of various forms of

uCDT belong to high-risk groups of obstetric and

perinatal pathology, and therefore they need close

monitoring during pregnancy, childbirth and the

postpartum period, and it is also necessary to examine

newborns who have a high probability of inheriting this

disease. The high incidence of complications during

pregnancy, childbirth and the postpartum period in

patients with uCDT determines the relevance of this

problem in obstetrics and the thoroughness of

examination of this category of women. However,

ambiguous and sometimes contradictory data on the

association and incidence of these complications with

uCDT require further research to determine a set of

diagnostic and preventive measures.

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Klemenov A.V., Tkacheva O.N., Vertkin A.L.

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ZBIRNIK

NAUKOVYKH

PRATS

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OBSTETRICIAN-GENECOLOGISTS OF UKRAINE

Vipusk 1/2 (33/34) 2014


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SJIF

I

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(2021:

5.

993

)

(92022:

6.

015

)

(2023:

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164

)

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Course of pregnancy and childbirth in connective

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P.4-7.

10.

Rudnikhina N.K., Vasilyeva A.V., Novikova I.M. et al.

Cardiac arrhythmias in pregnant women with

connective tissue dysplasia.

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Torshin I.Yu., Gromova O.A. Dysplasia of

connective tissue, cellular biology and molecular

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Filipenko P.S., Malookaya Y.S. Rol' dysplasia

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- P.13-19.

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Tsukanov Yu.T., Tsukanov A.Y. Varicose veins of

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№10 (2).

-

P.84 - 89.

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Kisters K., Barenbrock M., Louwen F. И соавт. –

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Khudoyarova D., Shodiklova G., Yunusova Z.

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TISSUE DYSPLASIA IN OBSTETRICS //Естественные

науки в современном мире: теоретические и

практические исследования. –

2024.

Т. 3. –

№. 1.

С. 13

-16.

17.

Adkhamjonovna Q. M., Zarnigor Y. Mathematical

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Pedagogical Inventions and Practices.

2022.

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С. 35

-38.

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Nuralievna S. N., Maqsadovna Y. Z. Ortiqcha vazni

bor ayollarda homiladorlik va tug’ruqning kechis

hi

va asoratlari //Ta’lim fidoyilari. –

2022.

Т. 22. –

№.

7.

С. 429

-438.

19.

Maqsadovna Y. Z. Pregnant women with morbid

obesity: pregnancy and perinatal outcomes

//Eurasian Medical Research Periodical.

2023.

Т.

16.

С. 72

-77.

20.

Khudoyarova D., Abdullaeva S. FETOPLACENTAL

INSUFFICIENCY

WITH

HYPOTENSION

IN

PREGNANT WOMEN //Естественные науки в

современном

мире:

теоретические

и

практические исследования. –

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С. 42

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References

Bukharin O.V., Chepalchenko O.E., Valyshev A.V. et al. Microflora of the large intestine in patients with connective tissue dysplasia. J. Microbiol. Epidemiol. Immunobiol. – 2003- №3. - P.62-66.

Gracheva O.N. Dysplasia connective tissue - prevention of gestational complications. Gin. Akush. and Perinatol. - 2010. - № 3, pp. 25-29.

Golovskoy B.V., Usoltseva L.V., Khovaeva Y.V. et al. Features of the clinical manifestation of connective tissue dysplasia in people of working age. J. Klin. honey. - M. - 2002 - No 80(12) - P.39-41.

Zakharyan A.L., Zakharyan E.L. Severity of varicose veins of lower limbs in various degrees of connective tissue dysplasia. G. wedge. Hir. – 2005. - No8 - P.42 - 44.

Zemtsovskiy E.V. Dysplastic phenotypes [Dysplastic phenotypes]. Dysplastic heart. St. Petersburg: "Olga" - 2007. - P. 68-90.

Kazachkova E.A., Tukay KS. Connective tissue dysplasia syndrome and pregnancy. Moscow, 2007. – 79 p.

Klemenov A.V., Tkacheva O.N., Vertkin A.L. Dysplasia of connective tissue and pregnancy (review). archive. - 2011. - № 11. - P.80-83.

Klemenov A. V. Undifferentiated dysplasia of connective tissue. Moscow, 2005. - 136 p. 129 ZBIRNIK NAUKOVYKH PRATS ASSOCIACII OBSTETRICIAN-GENECOLOGISTS OF UKRAINE Vipusk 1/2 (33/34) 2014

Komisarova L.M., Karachaeva A.N., Kesova M.I. Course of pregnancy and childbirth in connective tissue dysplasia. – J. Akush. and gin. - 2012. - No 3 - P.4-7.

Rudnikhina N.K., Vasilyeva A.V., Novikova I.M. et al. Cardiac arrhythmias in pregnant women with connective tissue dysplasia. – J. Akush. and gin. – 2012. - No.3.- P.97-100.

Torshin I.Yu., Gromova O.A. Dysplasia of connective tissue, cellular biology and molecular mechanisms of magnesium impact. – Zh. RMJ. - 2008.- Vol.16, No4. - P.3-11.

Filipenko P.S., Malookaya Y.S. Rol' dysplasia connective tissue v formirovaniya prolapsa mitral'nogo valvea [The role of dysplasia of connective tissue in the formation of mitral valve prolapse]. J. Klin. honey. Moscow, 2006. - No84(12) - P.13-19.

Tsukanov Yu.T., Tsukanov A.Y. Varicose veins of lower limbs as a result of connective tissue dysplasia. J. Angiol. vessel. Hir. -2004 - №10 (2). - P.84 - 89.

Kisters K., Barenbrock M., Louwen F. И соавт. – Membrane intracellular and plasma magnesium and calcium concentrations in preeclampsia // Am. J. Hypеrtens. – 2000. - Vol.13. №7. - Р. 765-769.

Dildora K., Zikiryaevna G., Zarnigor Y. PREGNANCY AND UNDIFFERENTIATED CONNECTIVE TISSUE DYSPLASIA //Central Asian Journal of Medical and Natural Science. – 2023. – Т. 4. – №. 6. – С. 1228-1232.

Khudoyarova D., Shodiklova G., Yunusova Z. RELEVANCE OF THE PROBLEM OF CONNECTIVE TISSUE DYSPLASIA IN OBSTETRICS //Естественные науки в современном мире: теоретические и практические исследования. – 2024. – Т. 3. – №. 1. – С. 13-16.

Adkhamjonovna Q. M., Zarnigor Y. Mathematical Quest as a Learning Activity //Journal of Pedagogical Inventions and Practices. – 2022. – Т. 9. – С. 35-38.

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