Evaluating serum elastin levels in striae gravidarum

Introduction

Striae gravidarum (SG) is considered to be the most common and disfiguring cutaneous complication of pregnancy. Prevalence of SG varies between 55 and 90%, and SG typically appears in the second and third trimesters [1]. SG occurs anywhere on the body, especially on the abdomen and breasts. The buttocks, thighs, axillae, legs, and hips are less commonly involved [2]. Lesions may vary in size and color, and the scars are typically a few centimeters in length and 1–10 mm in width [3]. Although SG does not cause serious medical problems, it may lead to itchiness and restlessness during pregnancy. As affected areas may become itchy, scratching them increases the risk of infection [4]. Over the long term, disfiguring SG may cause psychological distress, lack of self-confidence and represent an important aesthetic concern [5].

The pathogenesis includes genetic and hormonal factors as well as increased mechanical stress on connective tissue [6]. Many risk factors have been studied for their possible effect on the elasticity of the skin during pregnancy, including skin type and structure, race, family history, skinfold thickness, birth weight of the newborn, pre-preganancy body mass index (BMI), age, weight gain, impaired glucose tolerance, socioeconomic status, poor nutrition, type of delivery, and even eye and hair color [5], [6], [7]. However, the precise underlying etiology of SG remains unclear [2], [6], [7].

Elastin is a scleroprotein that has a texture similar to rubber but is 5 times more elastic. Extracellular matrix assures the structural support of the skin, and elastin plays an important role in the extracellular matrix. Alterations in elastin metabolism are included in the pathophysiology of destructive lesions affecting elastin-rich organs, such as blood vessels, kidney, skin, and lungs. Serum elastin levels are increased in emphysema, abdominal aortic aneurysm, and atherosclerosis [8], [9]. Although recent studies have shown changes in the structure of elastin in striae tissue in pregnant women [10], [11], there are no studies investigating elastin concentration in serum samples. The aim of the study was to investigate the role of elastin in the etiopathogenesis of SG.

Materials and methods

Results

Participants were separated into two groups due to the existence of the SG. The mean values were calculated for each of the variables under investigation among the groups. Comparisons of personal characteristics between pregnant women with and without SG are presented in Table 1.

Among 138 study participants, 105 (76.0%) had SG (Group 2), and 33 (23.9%) did not develop SG (Group 1). In Group 2, 32 had SG (30.4%) only in the abdomen; 15 (14.2%) had striae exclusively in other regions, such as hip, thigh, and breast; and 58 (55.2%) had SG in both abdominal and other regions. In the SG group, SG was developed most commonly after 20 weeks of pregnancy (80.0%). According to Davey scoring, the intensity of SG in Group 2 was as follows: 32 (30.4%) were mild, 54 (51.4%) were moderate, and 19 (18.0%) were severe.

We found no significant differences between groups regarding smoking habit and positive SG history in their family. In the SG group, the presence of acne during pregnancy was remarkably more common in the group without SG (p=0.023). The skin type (p=0.001) was also a significant factor in the development of SG (Table 1). SG was dramatically higher in the Type C group compared with Type A (p=0.006) and Type B (p=0.001), revealing statistical significance based on skin type.

Comparisons of variables between groups according to the development of SG are shown in Table 2. The average age in the SG group was remarkably lower than in the other group (25.34±3.44 years vs. 28.45±4.61 years, respectively; p<0.001). Prepregnancy BMI and postpregnancy BMI were significantly lower in the SG-negative group than in the SG-positive group. Additionally, abdominal circumference, hip circumference, and thigh circumference were significantly higher in the SG-positive group. There was no statistically significant difference between groups about weight gain during pregnancy and daily water consumption.

Significantly higher serum elastin concentrations were found in pregnant women with SG compared to pregnant women without SG (99.46±32.92 μg/mL vs. 88.36±19.12 μg/mL, respectively; p=0.018) (Table 2).

Comparisons of birth parameters between groups based on the presence or absence of SG are shown in Table 3. Weight at birth and head circumference were significantly higher in the SG-positive group (p<0.001 and p=0.001; respectively). Additionally, significant differences were found between the two groups with regard to infant sex. Male babies were significantly higher in the SG-positive group than in the SG-negative group (p=0.037). No noteworthy differences were noted between 2 two groups with regard to gestational age at birth and mode of delivery (p=0.624 and p=0.579, respectively) (Table 3).

Backward LR logistic regression analysis was performed between parameters that were statistically significant according to univariate analysis, such as the sex of the baby, acne condition, skin type, baby’s weight and head circumference, mother’s age, elastin level, and anthropometric measurements, with a correlation of 0.7 or greater. Other parameters included the mother’s height, weight, BMI, weight gain, thigh circumference, hip circumference, and abdominal circumference. Our results showed that increased elastin level, acne presence in mother, higher BMI after birth and male infants increases the risk of SG. In the other hand, the risk of SG decreases as maternal age increases (Table 4).

Discussion

Although SG does not cause serious health problems, it is difficult to manage given aesthetic concerns, psychological problems, and inability to predict the occurrence of SG, and the lack of definitive treatment SG is noted in 50–90% of pregnancies [1], [2], [3]. In this study, the frequency of SG is 76%. We noted that SG was linked with young maternal age; pre- and postpregnancy maternal weight and BMI; anthropometric measurements, such as hip, abdominal and thigh; acne presence during pregnancy and skin type, which are coherent with previous study results [6], [7].

In addition, male babies, high birth weight and head circumference of the newborn are associated with SG. In contrast with previous studies [1], [2], [5], we did not determine any relationship between SG and smoking, family history, weight gain during pregnancy and daily water consumption.

As far as we know, mechanical skin tension and increased estrogen, relaxin and adrenocortical hormone levels affect elastin fibers, collagen fibers and other extracellular matrix components and cause abnormalities that trigger the development of SG [13], [14], [15]. Hormones, such as adrenocortical hormone and relaxin, reduce the adhesion between collagen fibers, which causes structural alterations in elastin fibers and collagens and leads to reduced solidity to tension [16], [17]. The studies showed that androgen, estrogen and glucocorticoid receptors were 2 times more frequent in striae tissues compared with normal skin. This evidence indicates increased hormonal receptor activity in skin areas that are exposed to mechanical tension [18]. Hereby, increased skin tension may lead to the degeneration of the skin at the striae zones. Increased glucocorticoids during pregnancy suppress the production of the collagen and elastin fibers, thus preventing renewal of the fibers, which adapts the skin to mechanical stress.

However, despite a large number of studies, it is still difficult to pinpoint the exact cause of striae formation and predict its occurrence. Once the striae is formed, the deformation of the skin is irreversible. The most effective method in the treatment of SG is to prevent its development by using prophylactic treatments. But according to the Cochrane Review, one of the largest studies ever made about SG, topical agents have been reported to be unsuccessful in preventing the development of SG [19].

This research has shown that the reason behind the development of SG still remains unclear and further research is needed to clarify the etiopathogenesis to develop effective agents for prevention. The focus of our study was on the role of elastin turnover in the etiopathogenesis of SG.

Elastin is an important scleroprotein located in connective tissue, providing elasticity to skin upon exposure to mechanical stress. In our study, serum elastin levels, which is an indicator of elastin turnover, were significantly higher in SG-positive women than in women without SG. High serum elastin levels may be the result of a induced elastin production in women with SG. Wang et al. investigated the anatomy of elastic fibers in striae from healthy and lesional skin of pregnant women. The authors observed that a significant remodeling of the cutaneous elastic fiber system occurred as a consequence of the increased low-intensity load on the skin during pregnancy [11]. Due to these alterations, there was a marked disruption of the normal elastic fiber network. Elastin is produced by linking together many small soluble precursor tropoelastin protein molecules. Interestingly, the expression of the tropoelastin gene was dramatically elevated in SG [11], indicating that a considerable amount of tropoelastin-rich fibrils were derived from de novo synthesis by dermal fibroblasts. Amplification of the synthesis of tropoelastin and fibrillin-1 may represent the skin’s response to the disruption of normal elastic fibers, and this feature may promote increased serum elastin in SG as show our study.

Although the level of elastin is increased in tissue and serum, newly synthesized tropoelastin-rich fibers cannot function as elastin fibers because they are thin and disorganized [20]. Therefore, high elastin levels in serum cannot prevent the formation of striae; conversely, it may represent the production of elastin caused by mechanical tissue damage. Similar results were reported by Watson et al., who observed a complex, nested elastic system in the normal skin [14]. However, they implied that in skin affected by striae, the components of this elastic fiber network were reduced and reorganized. In this setting, the elements of fibrillin and elastin were affected equally. Mechanical pressure on the skin during pregnancy can influence the elastic fiber network and trigger the remodeling that leads to the formation of striae [14].

The most important limitations of our study are that we did not investigate elastin-derived peptides (EDP), which is known as another marker of elastin turnover. Production and destruction rate of elastin fibrils increases with the development of striae [11], [14], resulting soluble elastin peptides to pass into bloodstream which may increase the serum EDP level. Although studies have used EDP as an indicator of elastin turnover in atherosclerosis and aortic aneurysm [21], there is no study found investigating the EDP level in SG in the literature. If we studied the level of serum EDP in our study, we could show both the production and destruction of elastin in a bidirectionally. However, our hypothesis was that the most important factor in the stria etiopathogenesis in pregnant women was the problems caused by the production of elastin rather than destruction. Therefore, we evaluated only the serum elastin level, assuming that it would reflect the production of elastin better. Since our study is the first study in which serum samples are used to analyze SG, we believe that our study will inspire researchers to investigate other markers of elastin turnover.

The other limitations of the present study include data restricted to the experience of a single center and possible impacts of genetic, metabolic and environmental factors on serum elastin levels.

To our best knowledge, there is no study designed to evaluate serum elastin levels in pregnant women with SG. Our results revealed high serum elastin levels in women with SG as a marker of increased elastin turnover. These findings are in conjunction with previous studies that indicate the critical role of elastin in the striae formation. Since striae development during pregnancy is influenced by many variables such as genetic structure, skin type, age, BMI, weight gain and gender, serum elastin level is not suitable for clinical purposes to predict the occurrence of SG. Considering all risk factors including elastin levels, SG may be predicted more accurately. In addition, many topical medical agents and laser treatment modalities that prevent or heal the deformed skin are available that are specially designed to stimulate collagen production. However, very few of these treatment modalities have focused on elastin production [20]. Better treatment options that protect the skin structure under mechanical stress and increase the production of healthy elastin may be developed as the number of studies investigating the role of elastin in SG development increases.

In conclusion, serum elastin levels are increased in women with SG. However, the newly synthesized elastin may not be functional as it is thin and disorganized. Therefore, increased elastin production may not prevent the formation of striae. High serum elastin levels in SG may be used for clinical purposes to predict the formation of striae and this finding may provide an impetus to explore the pathomechanisms of striae. Further controlled trials on larger series are warranted to determine the predictive role and clinical significance of serum elastin levels in the formation of SG.