Pregnancy leads to the development of conditions that result in significant physiological, structural, and functional changes in various parts of the body to adapt to this phenomenon. While many of these changes resolve after pregnancy, some may persist permanently, subsequently exerting a significant impact on women’s lives [1]. One of these changes is skin alterations that occur in most women [2]. Skin changes during pregnancy are due to hormonal and metabolic changes, which are categorized into three groups: pre-pregnancy skin diseases, physiological skin changes during pregnancy (including increased skin pigmentation, melasma, changes in hair growth, vascular changes, and striae), and pregnancy-specific skin diseases [3]. Skin changes during pregnancy include increased pigmentation due to melanin deposition in the skin, affecting 90% of pregnant women [4]. This change is more pronounced in women with darker skin tones and is most noticeable in the early stages of pregnancy and in naturally darker areas like the areola, perineum, and navel [5]. Vascular changes in pregnancy, due to increased blood volume and flow and reduced peripheral vascular resistance, include spider angiomas and palmar erythema [6]. Spider angiomas, seen in two-thirds of white women and 10% of black women, are characterized by fine, red protrusions with branching vessels from a central lesion, often observed on the face, neck, and upper chest, and usually resolve after childbirth [7]. Palmar erythema is another change that is clinically insignificant, seen in two-thirds of white women and one-third of black women, and typically diminishes shortly after childbirth [5, 8]. Melasma is a common skin change during pregnancy, affecting 50% of pregnant women, characterized by irregular brown patches on the face, neck, and forehead [3, 9]. The exact cause is uncertain, but it is thought that both environmental and genetic factors may contribute. These patches usually fade after childbirth [5, 9]. Hair growth changes in pregnancy include an increase in the anagen phase compared to the resting phase. Estrogen prolongs the growth phase, while androgens cause follicles to lengthen in androgen-dependent areas like the face and neck [10]. Sudden hair loss during the telogen phase typically starts one to five months after childbirth, with hair growth returning to its pre-pregnancy state within six months to a year after childbirth [7, 10]. Striae are the most common changes in connective tissue that occur during pregnancy, typically appearing in the third trimester and impacting women of any race, whether they are first pregnant women or have had multiple pregnancies [11]. They form on the abdomen, thighs, and breasts, beginning as red or purple streaks that progress into glistening silvery lines, manifesting as creases on the surface of the skin [2, 11]. These pregnancy striae can be several centimeters long and 1–10 millimeter wide [12]. These symptoms can be noticed in 50–90% of pregnant women before 24 weeks and are also prevalent in 50–90% of the general population [13, 14]. In Iran, the prevalence of these skin changes among pregnant women is around 87.7% [15]. Some women consider these symptoms to be normal pregnancy symptoms. The exact cause is still not fully known. It is believed that genetic and hormonal factors, as well as increased mechanical pressure, play an important role in their development [16]. They can also occur as a result of rapid weight gain, specific endocrine disorders, and prolonged use of steroids [1, 17]. Striae are rarer in Asian and African American women, indicating a genetic influence [2, 17, 18]. Hormones such as estrogen and epinephrine are thought to contribute to their development. Estrogen, relaxin, and adrenal gland hormones can decrease collagen fiber connections and increase the extracellular matrix, contributing to striae development in areas under tension [18]. Additionally, there is a notable increase in estrogen, androgen, and glucocorticoid receptors in striae [19]. During pregnancy, estrogen hormone levels increase significantly moreover. The level of epinephrine hormone in pregnant women is higher compared to normal individuals and increases during pregnancy. Also in early pregnancy, the level of relaxin hormone is at its highest. This hormone works to relax the muscles and help facilitate the easier passage of the baby during childbirth [5, 19, 20]. Striae form following sudden weight gain, specific endocrine conditions, and prolonged steroid use [16, 20]. Continuous mechanical pressure on skin tissue alters the elastin fiber network and affects skin elasticity [19, 20]. They result from tension and increased mechanical pressure on the connective tissue, causing skin stretching and inadequate collagen repair disrupted by tension [11, 20]. Changes in the elastin fiber network affect the damaged skin’s viscoelastic properties, leading to firmer skin with reduced elasticity and deformability compared to normal skin [7, 19, 20]. Individuals in this situation are at higher risk of pelvic organ prolapse and tears in the perineal and labial areas during childbirth [19, 20]. Pregnancy striae can be affected by factors such as the age of mother, body mass index (BMI), weight gain, abdominal size, baby weight, family background, and nutrition [21]. While not medically risky, they can impact self-image, confidence, and mental health. This may lead to issues such as negative body image, reduced self-confidence, and even depression [22]. These consequences can result in psychological challenges, poor body image, diminished sexual satisfaction and overall well-being, skin injuries from scratching, formation of itchy papules and plaques, persistent stress and anxiety for the, and potential behavioral issues for the infant [5, 7, 23]. Many primipara or women planning to have a child are seeking information on factors influencing the condition of stretch marks (striae) and how to prevent and treat them [2, 24]. They are ready to spend money on treatment options. Interventions for striae emphasize prevention and management [7, 24]. Actions for preventing and treating stretch marks include engaging in regular physical activity, maintaining a nutritious diet, staying well-hydrated, utilizing skincare goods, and therapeutic approaches such as microdermabrasion and microneedling. Nonetheless, some of these interventions may be costly and not be easily affordable for all individuals [19, 25]. Research conducted in Jiangsu, China, demonstrated that lifestyle choices and dietary habits play a crucial role in the development and intensity of striae on the skin [18, 19, 25]. A study conducted in Lebanon suggested that the topical application of lotion containing cocoa butter may not decrease the chance of developing pregnancy striae [26]. A study has shown a link between the presence of striae and blood levels of vitamin C [27]. Limited evidence suggests that centella and bitter almond oil massage may help prevent and reduce the severity of striae (SG). There is weak evidence supporting the use of hyaluronic acid for preventing SG. Tretinoin may also reduce the severity of new striae, but its use is restricted by its pregnancy category [28]. Some studies have shown the possible effects of certain vitamins, such as vitamin C, on the appearance of stretch marks [29, 30]. Vitamin C, also known as ascorbic acid or ascorbate, is a water-soluble vitamin that acts as an antioxidant and reviving agent in the body and has a chemical structure of a 6-carbon lactone. The deterioration of vitamin C happens quickly when exposed to air [5, 30]. Vitamin C is a crucial component in the diet of humans and many animals, the lack of which can result in scurvy and non-healing wounds [31]. The skin has a significant amount of vitamin C (the concentration of the substance in the tissue ranges from 0.4 to 1 milligram per 100 grams of wet tissue weight), mainly found in the endocellular compartments. It is delivered to the layer of skin through blood vessels [32]. Daily vitamin C intake during pregnancy should be between 80 and 85 mg, which is about 20% higher than when not pregnant. The United States Food and Drug Administration (FDA) classifies vitamin C as category A; consuming more than the recommended amount is considered category C [5, 33, 34]. Humans, in spite of plants and some animals, are incapable of synthesizing it because they do not have the enzyme L-gluconogama lactone oxidase. While high concentrations of vitamin C supplements are found, only a small amount of it is naturally present and active in the skin. It is a potent antioxidant that aids in shielding the skin from aging, ultraviolet (UV) damage, and immune system suppression, as well as helping to prevent carcinogenesis [35]. Vitamin C has anti-aging properties by increasing collagen synthesis and reducing its degradation. It also helps in reducing the development of melanin and pigmentation, and enhances the process of wound repair [21, 30, 35]. This vitamin inhibits the aP-1 (activation protein-1), and decreases the production of matrix metalloproteinase (or matrix metalloproteinase (MMP): an enzyme that breaks down collagen) and hinders the natural production of elastin [5, 21, 35]. There is still limited research on the effects of different types of topical vitamin C formulations on the human skin and more research is needed [21, 30, 35]. Some research has also proposed a potential impact of certain vitamins, such as vitamin D, on the formation of striae distensae. This vitamin is a fat-soluble vitamin that belongs to the tocopherol family. The main compounds within this group are vitamin D₃ and vitamin D₂ [36, 37]. The primary source of vitamin D is sunlight, particularly ultraviolet B rays, which trigger a chemical reaction in the deeper layers of the epidermis, resulting in the production of cholecalciferol or vitamin D₃ [38]. 1,25-dihydroxy vitamin D plays a significant role in calcium homeostasis and bone health. It is biologically active and serves as a stable indicator of the level and status of vitamin D in the body [39]. Additionally, it helps maintain the permeability barrier of the epidermis and stimulates the proliferation and differentiation of keratinocytes in the epidermis, as well as the growth of fibroblasts in the dermis. It is worth noting that fibroblasts are the main cells in the dermis responsible for producing collagen and the extracellular matrix [1, 39]. Therefore, vitamin D deficiency and collagen deficiency are directly related to the occurrence of stretch marks [32, 40]. Collagens, which are produced by dermal fibroblasts in the extracellular matrix, are essential for skin health. Among the various types of collagens, type 1 and type 3 are particularly important and make up 80–90% of the dermis [25, 35]. Considering all the mentioned factors, the contradictory results regarding the efficacy of interventions, limited research on vitamin consumption, high prevalence of this condition as well as expensive costs of cosmetic goods and medical treatments, conducting a study aiming to find out the impact of vitamin “C + D” combination cream on striae in primipara seems essential. This research would not only provide valuable insights into the most effective strategies for preventing and reducing striae but also offer important recommendations to the target population. It would represent a crucial effort in enhancing the well-being of expectant pregnant women and, in turn, benefiting families and society as a whole.

The majority of individuals in the vitamin “C + D” group fell within the age brackets of 25–30 and 35–40 years, whereas in control group, the age range was 30–35 years. After the intervention, their BMI ranged from 25 to 29.9 (Table 1). The vast majority of the samples in both categories had no prior experience of abortion and family history of striae in the immediate family members and had white skin tone (Table 2). Finally, based on Table 1, the findings indicated that there was no notable distinction among the factors of age, level of education, financial status, and body mass index following the implementation of the two groups (p $>$ 0.05). In accordance with Table 2, the results demonstrated that there was no notable disparity in the skin color, abortion history, and familial history of striae between the two groups (p $>$ 0.05). The two groups showed no significant differences in terms of demographic and obstetric features, such as age, education level, economic standing, body mass index post-intervention, abortion history, skin color and history of striae in immediate family members (p $>$ 0.05).

Table 3 presents the occurrence of pregnancy striae and their comparison in the two groups under investigation. Since pregnancy striae did not follow a normal distribution based on the Kolmogorov-Smirnov test, the non-parametric Mann-Whitney test was used to compare the two groups. Following the implementation of the intervention, notable disparities were noted in the incidence of striae among the two groups at weeks 4 (p 0.001), 8 (p 0.001), 12 (p 0.001), and 16 (p 0.001) (Table 3).

The findings suggest that the use of vitamin “C + D” cream could potentially have a positive impact on reducing the development of pregnancy striae in primipara. Further studies are needed to confirm these results and explore the specific mechanisms by which vitamin “C + D” may be beneficial in preventing striae formation during pregnancy, a study by Abdolbaghiyan and colleagues in 2020 titled “Expression changes of collagen І and ІІІ genes in human skin fibroblast cells due to microalgae extract Chlorella vulgaris and its comparison with vitamin C” conducted at the National Institute of Iranian Genetic and Biological Resources, showed that algae extract and vitamin C increased collagen type І expression by 3.14-fold and 1.42-fold, respectively [35]. Chlorella vulgaris algae extract significantly increased the expression of collagen type І gene, while vitamin C significantly increased the expression of collagen type ІІІ gene, increasing the expression to 2.12-fold. They are emerging as promising substitutes to detrimental chemicals in stimulating collagen production [35]. These results support the idea of vitamin C being beneficial for collagen synthesis and its potential role in conditions such as striae in pregnancy.

A 2018 study by Hajhashemi and colleagues [43] evaluated the effectiveness of aloe vera gel and sweet almond oil on stretch marks in 160 new women. they found that creams containing aloe vera and sweet almond oil were effective in reducing striae erythema compared to the base cream. Additionally, these creams alleviated itchiness and inhibited the advancement of striae (p 0.001). The findings of this research align with the results of the current research in relation to the impact of topical compounds on the severity of striae erythema in pregnancy. Moreover, aloe vera gel contains vitamin C, and this letter can be considered given the impact of it on collagen production and its role in the skin. Almond oil, on the other hand, is a great source of vitamin D [36]. However, it is important to note that this correspondence cannot be fully stated, since vitamin C and vitamin D were not used alone in the research.

Research by Hocaoglu et al. [1] in 2020 aimed at Association between serum 25-hydroxyvitamin D levels and the presence and severity of striae gravidarum on 91 primigravid women showed that women with normal levels of serum 25-hydroxyvitamin D ($\ge$30 ng/mL) are at a lower risk of developing striae. The result of this research on the role of serum vitamin D levels, in relation to the occurrence of pregnancy striae is consistent with the findings of this research. Using topical vitamin D and absorbing it through the skin can reduce the risk of pregnancy striae [1]. However, it is important to note that the mentioned study is correlational and only reports the relationship between serum vitamin D levels and pregnancy striae.

In 2020, Sadat et al. [44] conducted a research with the aim of assessing the impact of sesame oil and almond oil on the occurrence of striae in 165 pregnant women. At the end of the 36th week, the findings showed that the incidence of striae in the almond oil, sesame oil and control groups was 63.60%, 60% and 58.20%, respectively. There was no significant difference in the incidence of striae gravidarum between the three groups at the 36th week of pregnancy (p = 0.83). Finally, it was concluded that both sesame oil and almond oil cannot be effective in preventing the occurrence and severity of striae gravidarum. Sesame oil and almond oil both contain vitamin D, the finding of this research does not agree with the results of this study regarding the use of vitamin D on the occurrence of striae in pregnancy. In this research, blinding was not done and the control group did not use any placebo, and the samples were massaged for 5 minutes after applying the oil, which can be effective in creating bias in the study results and the possible cause of inconsistency in the results [44]. Taheri et al. [45] conducted a research with the aim of determining the effect of vitamin C cream on pregnancy striae, showed that use of Vitamin C cream had a significant effect in reducing number and severity of pregnancy striae (p 0.001). The results of this study confirmed the effectiveness of vitamin C in preventing pregnancy striae in women. Using topical vitamin C and absorbing it through the skin can reduce the risk of pregnancy striae and combined vitamin C + D cream is more effective on striae than a vitamin C cream alone. This can be due to vitamin D and its effects on the occurrence of striae in pregnancy [45].

A study by Taavoni et al. [12] in 2011 aimed at assessing the effects of olive oil on striae gravidarum on 70 nulliparous women in the second trimester of pregnancy showed that striae occurred in 40% of women using olive oil, while striae were noted to occur in 50% of the control group. There was no significant difference between the intervention and control groups. The study notes that the use of olive oil until the end of the second trimester of pregnancy was not effective in reducing the occurrence of striae gravidarum (p = 0.11). Olive oil contains vitamin D and C. The finding of this research does not align with the results of study based on the use of topical compounds for the occurrence of pregnancy striae and are not in harmony. However, in this study, blinding was not done, and the control group did not use any placebo. These actions can potentially bias the study results, which may be the reason for the lack of alignment [12]. However, it is important to note that this interaction cannot be fully stated, since vitamin C and vitamin D were not used alone in the research. In the final analysis, studies consistent with the current research suggest that vitamin D performs a crucial task in skin, such as epidermal and fibroblast growth, and the humoral and cellular immune system [39]. Fibroblasts are the main cells in the dermis that produce collagen and the extracellular matrix [1]. In other words, collagen is produced by dermal fibroblasts in the extracellular matrix, and among its various types, type 1 and 3 collagens are very important in the skin and make up 80–90% of the dermis [35]. Moreover, this vitamin reduces cellular apoptosis and excessive proteolytic activity in the epidermis, thereby improving skin hydration [32]. Ultimately, it can be said that a deficiency in this vitamin leads to a deficiency in collagen synthesis, ultimately playing a role in the occurrence and severity of striae [1]. Especially during pregnancy, the need for this vitamin increases. Regarding vitamin C, it can also be said that this vitamin and its derivatives play a significant role in collagen synthesis and skin strengthening [21]. This vitamin plays an important role in maintaining the collagen network of the skin by preventing the inactivation of two enzymes, prolyl and lysyl hydroxylase, which are of great importance in collagen production [32]. This vitamin is an essential component for prolyl and lysyl hydroxylases that catalyze the production of hydroxyproline and hydroxylysine. Also vitamin C has been shown to inhibit the activation of aP-1, which leads to a reduction in MMP production and collagen damage [21]. Vitamin C also directly activates the transcription factors involved in collagen synthesis and stabilizes procollagen messenger RNA (mRNA) that regulates type 1 and 3 collagen synthesis [35]. In addition, vitamin C increases the gene expression of collagen and synthesis of the tissue inhibitor of MMP-1 (matrix metalloproteinase-1), which decreases collagen degradation [32]. In-vitro studies have also shown that vitamin C inhibits the biosynthesis of elastin. in animal studies, application of 5% ascorbic acid two hours prior to UV exposure was found to reduce skin wrinkling. Finally, its anti-aging effect involves increasing the synthesis and stabilization of collagen fibers and reducing their degradation [21]. We can say that the strength of this study was the presence of a placebo group, random candidate assignment to different groups, and blinding and concealing the candidates. Some of the constraints of this research include: it was not possible to accurately regulate the number of times the cream is used by candidates, there was a lack of information about the vitamin C and D serum levels in the samples. Further research is recommended to investigate the benefits of these creams in the treating postpartum striae, as well as their potential applicability to other populations such as persons seeking weight changes and athletes concerned about developing striae. The target groups of this study include primipara, specializing in obstetrics/gynecology, midwives, healthcare professionals, and officials and planners responsible for educational and supportive programs for pregnant. Given that supporting pregnant is a key aspect of midwifery and healthcare, one way to assist them is by preventing and treating pregnancy striae. Considering the high prevalence of striae in pregnancy and the high costs of cosmetic and medical treatments, the use of vitamin supplements can be very beneficial. Providing pregnant with adequate information about striae is essential to reduce their anxiety and worries. In this study, a cream containing vitamins C and D was used, and future studies should also consider the use of other vitamin products, such as a combination of vitamins E and C, to determine their impact on striae. Additionally, the effectiveness of this cream should be investigated, especially in women who have had multiple pregnancies.

In summary, the findings of this study demonstrate that vitamin C and D cream had an impact on diminishing the prevalence and intensity of pregnancy striae and also affected the timing of their appearance.

The datasets used and analyzed during the current study available from the corresponding author on reasonable request.

HT and MK designed the model and the computational framework and analyzed the data. HT carried out the implementation. HT and SH performed the calculations. HT and MK wrote the manuscript with input from all authors. HT and AG prepared the creams. HT and NE did the sampling. HT and MK and AG and NE and SH conceived the study and were in charge of overall direction and planning. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

This study was approved by the ethics committee of Iran University of Medical Sciences (Approval code: IR.IUMS.REC.1401.215) and with Iran clinical trial site (registration number: IRCT20220509054799N1). Informed consent was obtained from all the candidates. This study was conducted in accordance to relevant guidelines and regulations.

This article is the result of the information obtained from the master’s thesis of midwifery education of Iran University of Medical Sciences and research project 3-1400-3-3-22271 of Iran University of Medical Sciences. The research team expresses its great gratitude to the respected research vice-chancellor of Iran University of Medical Sciences, and the authors also express their gratitude to the Clinical Research Development Unit of Shahid Akbarabadi Hospital, Iran University of Medical Sciences for conducting this research during the study period (IR.IUMS.REC.1401.215).

This work is granted by the Research Deputy of Iran university of Medical Sciences (22271-3-3-1400).

The authors declare no conflict of interest.