1. Introduction

Undifferentiated connective tissue dysplasia (UCTD) is currently considered one of the most common and underestimated multisystem conditions, especially in women of reproductive age. According to various authors, signs of UCTD occur in 20–40% of women of childbearing age, but in clinical practice it is diagnosed in less than 10% [1-2].

Connective tissue amounts to 60% of the human body mass and participates in the construction of all organs and systems: cardiovascular, respiratory, musculoskeletal, genitourinary, including reproductive. Its structural insufficiency can be the basis for the pathogenesis of a number of obstetric and perinatal complications.

The increased interest to this pathology is caused by the following factors:

• the high prevalence of UCTD in the population;

• non-specificity and polymorphism of the clinical presentation;

• insufficient awareness among obstetricians and gynecologists;

• increased frequency of complicated pregnancies, deliveries and adverse perinatal outcomes;

• risk of developing dysplasia in offspring.

Research of UCTD has intensified in recent years, but it is mainly descriptive or localized in nature, most often addressing individual aspects (e.g., the impact of joint hypermobility or valve prolapse on pregnancy).

In international practice, UCTD is distinguished as an independent clinical category using the Beighton score for assessing joint hypermobility and the comprehensive criteria according to Villefranche (1998), which was revised in 2017 [3].

Studies show an association between UCTD and mitral valve prolapse, varicose veins, premature birth, and isthmic-cervical insufficiency (ICI) [4].

Kozlova N.M. et al. (2021) showed that in women with UCTD, the frequency of threatened miscarriage is more than 50%, and in women with ICI, the incidence is up to 40%. Belyaeva Yu.Yu. (2020) studied placental insufficiency in women with dysplasia and proved an increased risk of fetal hypoxia. Khusnullin S.K. noted the need for early detection of UCTD in pregnant women with asthenic phenotype and complaints of rapid fatigue, back pain, varicose veins [5-7,2].

However, most studies do not employ a comprehensive interdisciplinary approach. There are also few studies that use objective morphogenetic, cardiometabolic, and echographic assessment methods in pregnant women with UCTD.

The aim of the research was to study clinical manifestations, features of pregnancy and birth outcomes in women with undifferentiated connective tissue dysplasia.

2. Material and Methods

The study was prospective and was conducted at the 9^th maternity complex in Tashkent. We examined 202 pregnant women who were treated at our clinic between 2022 and 2024. All patients were divided into two groups. The main group (n = 102) consisted of women with a confirmed diagnosis of UCTD (according to the criteria of cartilaginous, cutaneous, vascular, musculoskeletal symptoms, Beighton index ≥ 4). The control group (n = 100) consisted of healthy women without signs of dysplasia, matched for age and gestational age. Clinical history, physical status, ultrasound data, Dopplerometry, cardiography, delivery, and the condition of newborns were evaluated. Statistical processing was carried out using the χ² criterion, according to which p<0.05 was considered significant.

3. Results

Asthenic body type among patients with UCTD was observed in 80 (78.4%) patients in the main group and in 32 (32.0%) cases in the control group. The asthenic or dysplastic somatotype is characterized by the following signs:

• tall stature with insufficient body weight (body mass index <18.5–20 kg/m²);

• narrow shoulders and chest, long limbs;

• severe thoracic kyphosis or scoliosis;

• narrow face with elongated features, thin lips.

These features reflect a systemic deficiency of collagen structures, which disrupts the normal formation of the musculoskeletal frame. The asthenic type is one of the most common external manifestations of dysplasia, is detected in most patients with UCTD and can be combined with postural hypotension, increased fatigue, pain in the muscles and back (Table 1).

Table 1. Prevalence of clinical signs

Hypermobility is an excessive volume of active and passive movements in the joints exceeding physiological limits. Clinical manifestations include: ease in performing "acrobatic" movements (for example, touching the floor with the palms of the hands while keeping the legs straight, hyperextending the fingers and knee joints); frequent subluxations, crunching and pain in the joints; increased risk of injury and strains; instability of the sacroiliac, knee and ankle joints. During pregnancy, hypermobility may be aggravated by the hormone relaxin, which increases the risk of cervical insufficiency, pelvic biomechanics disorders, and labor weakness. Joint hypermobility was found in 67 (65.7%) patients in the first group in our study, which was significantly higher than in the control group, where this indicator was 18 (18.0%) cases (χ² 40,73; p<0,05). The assessment was performed using the Beighton score and 4 points or higher considered diagnostically significant.

Venous system injury in women with UCTD is caused by weakness of the connective tissue framework of the venous wall and valve apparatus. It is clinically manifested by dilation of the subcutaneous veins of the lower extremities; a tendency to edema and heaviness in the legs; frequent bruising (hemorrhagic syndrome); hemorrhoids (especially in the third trimester). Pregnancy increases venous load, especially against a background of increased intra-abdominal pressure, making varicose veins a typical complication of UCTD. Such patients often need to wear compression hosiery and take venotonics. Varicose veins were found in the main and control groups: 42 (41.1%) versus 15 (15.0%) cases, respectively. (χ² 17,59; p<0,05).

Mitral valve prolapse (MVP) is one of the characteristic cardiac manifestations of UCTD, most often detected by echocardiography. The cause is a disruption in the structure of the fibrous ring and chordal apparatus of the valve. Clinical signs are as follows: cardialgia (pain in the heart area unrelated to physical exertion); blood pressure lability; tachycardia, extrasystole; panic attacks, syncopal states (in mitral valve syndrome). MVP during pregnancy may be accompanied by a decrease in the adaptive reserves of the cardiovascular system, which requires monitoring by a cardiologist. Mitral valve prolapse was diagnosed in the main group of patients, which amounted to 24 (23.5%) cases.

Cutaneous manifestations of dysplasia reflect a disruption in the synthesis of collagen types I and III and a decrease in the strength of the dermis. The examined women had: striae (stretch marks) - not only in areas of rapid tension (abdomen, chest), but also on the shoulders, hips, in the lumbar region, even before pregnancy; skin hyperelasticity — the skin stretches easily and slowly returns to its original state; thin, dry, and fragile skin — frequent microtraumas, slow healing. These symptoms are particularly pronounced in the third trimester and in the postpartum period, when the skin undergoes sudden changes in volume and pressure.

Skin changes were also more frequently diagnosed in the group of patients with UCTD in 38 (37.2%) cases.

Thus, the clinical profile of women with UCTD demonstrates a typical syndrome of systemic connective tissue failure, manifesting itself in the musculoskeletal, vascular, cardiovascular, and skin areas. These manifestations not only increase the risk of obstetric complications, but can also serve as a diagnostic guide for the timely detection of UCTD, especially during the initial examination of a pregnant woman.

A comparative analysis of pregnancy complications in patients of the main and control groups was conducted. The analysis showed that in the main group (n=102), compared with the control group (n=100), pregnancy complications occurred significantly more often according to all parameters presented (Table 2).

Table 2. Complications of pregnancy

The threatened abortion risk was recorded in 56.8% of patients in the main group, which was more than 2.5 times higher than in the control group (21.0%). The difference was highly statistically significant (p<0.001).

Isthmic-cervical insufficiency (ICI) was observed in 42.1% of women in the main group versus only 5.0% in the control one, indicating a pronounced tendency to cervical dysfunction in patients of the main group (p<0.001).

Placental insufficiency was detected in 36.2% of patients in the main group, which also significantly exceeds the similar indicator in the control group (12.0%, p<0.01).

Preterm birth was observed in 21.5% of patients of the main group, while in the control group it was only 4.0%. The difference was statistically significant (p<0.01), indicating a higher risk of preterm birth in women of the main group.

Preeclampsia was diagnosed in 26.4% of patients of the main group compared to 9.0% in the control group (p<0.05), which also reflects a higher frequency of vascular complications of gestation in the main group.

Next, a comparative analysis of the frequency of intrauterine growth restriction (IUGR) was conducted in patients of the main and control groups. The analysis showed that IUGR was recorded in 18.6% of patients in the main group, which was almost four times higher than in the control group (4.5%). The difference was statistically significant (p<0.05), indicating a higher risk of fetal-placental blood flow disorders and fetal growth retardation in women of the main group.

Thus, a cumulative analysis of pregnancy complications shows that patients in the main group have a significantly higher risk of both maternal (threatened miscarriage, ICI, preeclampsia) and fetoplacental complications (placental insufficiency, IUGR, preterm birth) compared to the control group.

Analysis of the presented data on the course and outcomes of childbirth in the main and control groups showed marked differences in most indicators.

Weak labor activity was observed in 34.3% of women in the main group compared to 10.0% in the control group (p<0.001). It indicates that patients in the main group were significantly more likely to experience uterine hypotension during labor, which might have required medication stimulation (Table 3).

Table 3. Peculiarities of childbirth

Cervical dilation abnormalities were found in 29.4% of women in the main group, which was more than 3.5 times higher compared to the control group (8.0%, p<0.01). This fact reflects a tendency toward discoordination of labor and functional insufficiency of the cervix in patients of the main group.

Postpartum hemorrhage was recorded in 18.6% of women in the main group compared to 5.0% in the control one (p< 0.05), indicating a higher probability of hypotonic complications in the postpartum period.

Cervical and vaginal tears occurred in 22.5% of women in the main group compared to 6.0% in the control group (p<0.01). It confirms the increased trauma of childbirth in women of the main group, which might be associated with discoordination of contractions and structural insufficiency of connective tissue.

The frequency of cesarean sections was also higher in the main group (24.5% vs. 12.0%, p<0.05). It reflects the increased frequency of complicated deliveries and the need for operative delivery in this type of patients.

Childbirth in patients of the main group was significantly more difficult, with a higher frequency of labor abnormalities, traumatic tears, postpartum hemorrhages, and surgical delivery, which indicated the adverse influence of the initial pathology on the course of labor and the postpartum period.

Analysis of outcomes for newborns in the main and control groups showed significant differences, reflecting the impact of complicated pregnancy and childbirth in patients of the main group:

The mean body weight of newborns in the main group was 2760 ± 240 g, which was ~350 g less compared to the control group (3110 ± 280 g). Weight loss indicates a higher incidence of intrauterine growth restriction and confirms the adverse impact of fetoplacental insufficiency.

Low Apgar scores (<7 points in the 1^st minute of life) were recorded in 15.6% of newborns in the main group versus 4.0% in the control group. This difference indicates a higher incidence of hypoxia and asphyxia at birth in children of the main group.

Newborns from mothers in the main group more often showed signs of intrauterine distress and hypotrophy, which was manifested in reduced body weight and more frequent low Apgar scores. These results correlate with the high frequency of pregnancy and childbirth complications in the main group and reflect their adverse impact on perinatal outcomes.

4. Discussion

The results obtained confirm that undifferentiated connective tissue dysplasia (UCTD) is a significant predictor of complicated pregnancy, childbirth, and adverse perinatal outcomes.

The clinical phenotype of women with UCTD was marked by typical signs of systemic connective tissue dysfunction: asthenic somatotype (78.4%), joint hypermobility (65.7%), varicose veins (41.1%), mitral valve prolapse (23.5%), skin changes (37.2%). These data are consistent with the results of studies presented in the literature, which indicate a high prevalence of asthenic and dysplastic phenotypes among women with UCTD and their association with obstetric pathology [5,8].

The high frequency of pregnancy complications in the main group (threat of miscarriage — 56.8%, ICI — 42.1%, placental insufficiency — 36.2%, IUGR — 18.6%) reflects a violation of the structural and functional integrity of the connective tissue elements of the uterus, vessels and placenta. Joint hypermobility and weakness of the collagen structures of the cervix can promote isthmic-cervical insufficiency, while vascular insufficiency and fetoplacental insufficiency can develop into placental insufficiency and fetal growth restriction. These pathogenetic mechanisms were previously described by De Paepe A. (2018) and Malfait F. (2017) [3-4].

Features of labor in women with UCTD included: weak labor activity (34.3%), abnormal cervical dilation (29.4%), postpartum hemorrhage (18.6%), frequent traumatic tears (22.5%), increased frequency of cesarean section (24.5%).

This pattern of complications demonstrates that functional failure of the myometrium and connective tissue structures of the birth canal is a key factor in birth complications.

Perinatal outcomes were also worse in the main group: the body weight of newborns was significantly lower (2760 ± 240 g vs. 3110 ± 280 g), and a low Apgar score <7 at the 1^st minute was observed in 15.6% of cases (vs. 4.0% in the control group). It confirms that systemic connective tissue dysplasia of the mother adversely affects fetoplacental function and the adaptive abilities of the newborn.

Thus, a comprehensive analysis of clinical, obstetric, and perinatal data shows that UCTD is a multisystem risk factor requiring early detection, dynamic monitoring and personalized prevention of obstetric complications.

5. Conclusions

Undifferentiated connective tissue dysplasia in women of reproductive age is associated with a high risk of complicated pregnancy and childbirth, including threatened miscarriage, isthmic-cervical insufficiency, placental insufficiency, IUGR and preterm birth.

The clinical profile of UCTD (asthenic type, joint hypermobility, varicose veins, mitral valve prolapse, skin changes) is a significant diagnostic marker for the early detection of patients at a risk.

The course of labor in women with UCTD is associated with an increased frequency of labor abnormalities, traumatic tears, and postpartum hemorrhage, often requiring surgical delivery.

Perinatal outcomes were more unfavorable in the main group: there was a decrease in the body weight of newborns and more frequent asphyxia at birth, which was associated with chronic fetoplacental insufficiency.

The identified features justify the need for early screening for UCTD, personalized management of pregnancy and childbirth, including prevention of ICI, placental insufficiency and obstetric hemorrhage.

Conflict of Interests’ Statement

The authors declare no conflict of interest.

This study does not include the involvement of any budgetary, grant or other funds.

The article is published for the first time and is part of a scientific work.

ACKNOWLEDGEMENTS

The authors express their gratitude to the management of the multidisciplinary clinic of the 9th Maternity Complex in Tashkent for the material provided for our study.

Ethical Approval and Consent to Participate

The Research Ethics Board of our institution does not require review or approval of case reports. Our research was carried out in accordance with the World Medical Association Code of Ethics (Declaration of Helsinki).

Source of Funding

Each of the authors has reviewed and approved this manuscript. None of the authors has a conflict of interest, financial or otherwise. This manuscript is original, no part of it has been previously published and is not being considered for publication elsewhere. The corresponding author agrees to accept full responsibility for authorship at the submission and review stages of the manuscript.

Ethical Aspects

All patients signed voluntary informed consent to participate. Personal data were encrypted and used only for scientific purposes.