Recently, the number of studies examining the relationship between delivery methods and atopic-allergic diseases has increased. Asthma, allergic rhinoconjunctivitis, AD, and food allergies are among the most studied diseases in this regard [1–7]. In a large number of these studies, delivery by CS was associated with increased risk of allergic rhinitis, asthma, and food allergy [1, 3–5]. However, there are also studies showing that these diseases, and AD, may be unrelated to delivery methods [3, 6, 7, 28]. In a meta-analysis of Bager et al. with 26 studies, it was observed that delivery by CS is associated with a moderate risk increase for allergic rhinitis, asthma, and food allergy but not with inhalant atopy or AD [29].
In this study, there were patients with pollen, dust, food, drug, bee allergy, and allergic asthma in the patient group with allergies. Due to the low number of patients in allergy subtypes, all allergic diseases were grouped under a single allergy group and compared in terms of delivery method. As a result, patients born by CS were found to be 3.3 times more likely to develop any allergies (Table 2). Although the precise molecular and cellular mechanisms underlying the relationship between delivery method and allergies are still not clarified, it is clear that the early formation and maturation of the infant microbiome has a significant impact on immune system development and prevention of allergic diseases.
While a few studies have suggested a potential link between delivery method and AD [30], the majority of studies have not yielded conclusive evidence to substantiate this association [3, 28, 29]. Of course, along with genetic and environmental factors, the age of the patient and other sociodemographic characteristics are also the factors that may affect this relationship. In the study, no significant relationship was found between the delivery method and AD (p = 0,864) (Table 2). The effects of sociodemographic characteristics and allergy status on AD were also examined in normal and cesarean births separately (Table 3). While gender, age, and CM did not have a significant effect on AD in both normal and cesarean delivery, PSE significantly increased AD in CS (p = 0,045). It has been stated in the literature that active smoking and exposure to passive smoke are associated with a higher prevalence of AD in both children and adults [31]. Although the mechanism of this relationship is not yet known, it is likely that smoking may cause AD indirectly by creating dysbiosis in the microbiota in addition to its direct effect on the immune system and skin barrier. Consequently, it can be concluded that PSE in patients born by CS enhances the susceptibility to AD by influencing the patient's microbiota, immune system, or other underlying mechanisms.
It was also observed that having allergies increased the risk of AD in both normal and CS delivery, but this risk was 3.1 times higher in CS (p = 0,038, 95% CI = 1,065-9.139) (Table 3). Although the mechanism of AD is not fully understood, interaction between various genes, defects in skin barrier, infectious agents, host environments, and various immunologic responses are among the possible factors [32]. In addition, extensive research in recent years has revealed the importance of allergens in AD [33]. The skin's immunological response to the allergens in AD involves a complex process involving both IgE-mediated immediate immune responses and T-cell–mediated delayed immune responses [34]. In this intricate mechanism influenced by multifactorial elements, the presence of a balanced microbiota associated with NVD appears to provide partial compensation for the occurrence of AD in patients with allergies.
There are also studies showing that dysbiosis can cause seborrheic dermatitis [35]. On this basis, the effect of microbiota on NAD group diseases cannot be ignored. Although the relationship between AD and delivery method is mostly examined in the literature, it is an open topic for investigation in other dermatitis group diseases. In the present study, patients with other dermatitis (seborrheic dermatitis, irritant contact dermatitis, nummular dermatitis, napkin dermatitis, neurodermatitis, and photocontact dermatitis) were formed into a single group because they were few in number. Dermatitis types with an allergic or atopic component were not included in this group. Therefore, the group was named as “non-atopic dermatitis”. In the study, it was observed that the method of delivery had no effect in NAD as in AD (p = 0,923) (Table 2). However, unlike AD, allergy had no effect on NAD, and NAD diseases were less common in normal-born children with a PSE (Table 4). Such an effect of smoking has not been reported in the literature; on the contrary, besides the irritation caused by the toxic substances produced by cigarettes, it damages the skin barrier by disrupting the blood flow and oxygenation of the skin [36]. Although this result in the present study seems to be related to the low number of patients, it is worth evaluating the potential distinct effects of smoking on the microbiota of normal and cesarean births through non-atopic pathways.
In addition to providing a physical barrier, the skin microbiota also plays a role in the immune function of the skin [21, 22]. Hence, it can be hypothesized that the method of delivery, which can alter the skin microbiota, could potentially heighten the vulnerability to ISD. Although there is no detailed study on this subject, the results of the present study will be a reference for more comprehensive studies. In the study, all bacterial, viral, and fungal skin infections were grouped together as “infectious skin diseases”. On the other hand, scabies, which is slightly higher in number, was examined separately. As a result, it was observed that ISD were more common in those born by CS (p = 0,057) (Table 2). On the contrary, scabies were found to be significantly more common in those born by NVD (p = 0,032) (Table 2). Assuming that the relationship of the infectious group with CS is related to the disrupted microbiota and thus to an impaired immune response, it will be necessary to mention distinct factors for the scabies group. The higher prevalence of scabies in NVD may be attributed to differences in the mechanism of parasitic diseases or to the presence of distinct sociodemographic characteristics among those who opt for normal birth, potentially leading to living in less hygienic and more crowded environments. Alternatively, although less likely, it could be hypothesized that the microbiome of normal births may provide a more favorable environment for scabies infestation.
The effect of sociodemographic characteristics and allergy on ISD is shown in Table 5. Here, while the infection rate of 0–3 and 3 + age group patients is similar and high in CS, this rate decreases from 21.2–10.3% in NVD. In studies (especially on the gut microbiota), it is noteworthy that the microbiota shows great changes until the age of 2–3 years [37]. Zhu et al. showed that the method of delivery still has an effect on skin microbiota even up to 10 years of age [38]. In the present study, the decrease in ISD cases in the 3 + age group among those born by normal birth may be attributed to the microbiome being gradually shaped to enhance its physical and immunological protective functions over time. The high skin infection rate up to 10 years of age in CS (26,8%) was also likely due to the long-term effect of the altered microbiota.
The presence of allergies appears to be associated with a reduced risk of ISD in patients delivered by CS (p = 0,037) (Table 5). Although the exact immunological mechanism is unknown, it is worth mentioning that the diligent care provided to allergic children delivered by CS and their upbringing in a more hygienic environment may have potentially contributed to a decreased risk of ISD. Although it is not statistically significant, CM also seems to decrease the risk of ISD in CS (p = 0,080). Of course, in addition to systemic and local factors, many genetic and sociodemographic factors and low number of patients may also be effective in the formation of these results.
Unlike the ISD group, age, CM, and allergy status had no effect on scabies. The determined sociodemographic characteristics also had no effect on allergy status as well as scabies in normal or cesarean delivery (Table 6). Of course, more comprehensive and detailed studies are needed to confirm the results and explain the possible mechanisms.
Limitations
The statistical significance was adversely impacted by the division of patients into smaller groups due to the extensive examination of numerous factors and diseases within the same study. For this reason, diseases were compared in normal and cesarean delivery categories separately. Further studies involving a large number of patients, which will be conducted separately for certain diseases and factors, will yield more significant results.