Allergic rhinitis is a chronic, non-infectious inflammatory response of the nasal mucosa caused by human exposure to allergens, manifested by symptoms such as itchy nose, sneezing, runny nose, and nasal congestion (1). The global average risk of allergic rhinitis has exceeded 20%, in which studies have reported that the proportion of children may be higher than that of adults (2), the majority of patients have symptoms before the age of 20 years, and nearly half of the patients develop symptoms at the age of 5–6 years in some countries (3, 4). Thus, the risk of pediatric allergic rhinitis is worthy of further attention. Medical therapy, specific immunotherapy, and surgery are the most commonly used methods for treating allergic rhinitis, while avoiding risk factors has always been the best option. In recent studies on risk factors for allergic rhinitis (3–5), cesarean section has been suggested as a risk factor for allergic rhinitis, and this method of delivery is significantly related to the risk of pediatric allergic rhinitis. Moreover, studies have shown that the rate of cesarean section is increasing (6–8), and the majority of countries remarkably exceed the reasonable rate of cesarean section presented by the World Health Organization (WHO) (10%–15%) (9). This finding is closely associated with the improvement of the socioeconomic level, the change in maternal health awareness, and the healthcare level (5, 10). The present systematic review and meta-analysis aimed to explore the relationship between cesarean section and the risk of allergic rhinitis in children, as the global demand for cesarean section has significantly increased. In addition, Cuppari et al. (11) found that cesarean delivery influences the risk of atopy but does not affect the prevalence of immune sensitization and allergic diseases.

Allergic rhinitis is a chronic and refractory disease that can be caused by a variety of factors. Studies have shown an association between C-sections and the risk of allergic rhinitis in children. In this study, systematic review and meta-analysis were conducted to investigate the relationship between cesarean section and the risk of allergic rhinitis in children. The results may guide pregnant women to choose their delivery methods, suggesting that choosing a natural delivery may reduce the risk of allergic rhinitis in children, especially in high-risk areas.

The protocol of this meta-analysis was prospectively registered at https://www.crd.york.ac.uk/prospero/#recordDetails(CRD42022378094) on 3 December 2022.

Figure 1 shows the PRISMA flowchart for this meta-analysis. After searching through the proposed search strategy, a total of 1,722 articles were initially retrieved. After removing duplicate studies and reviews, 524 studies were obtained. Next, 481 articles were excluded due to irrelevance after evaluating their titles and abstracts, and the full texts of 43 studies were reviewed. Subsequently, 24 studies were excluded because they did not meet the inclusion criteria. As a result, 19 studies were included in the meta-analysis. These 19 studies were published in the English language, including 13 cohort studies and six cross-sectional studies. Among them, 10 studies directly examined the association between cesarean section or different modes of delivery and the risk of allergic rhinitis. Meanwhile, the other nine studies assessed the association between cesarean section or different modes of delivery and allergic disease or asthma, including allergic rhinitis.

Allergic rhinitis is a respiratory disease that can be affected by several factors. This meta-analysis examined the relationship between cesarean section and the risk of pediatric allergic rhinitis. As a result, the disorder of physiological bacterial colonization in children, especially in the gastrointestinal tract, affects the immune system (30), hinders the transformation of neonatal Th2 to Th1-biased T cell memory (31), and thus causes an increased risk of allergic diseases. Several studies on cesarean section have shown that delivery via cesarean section might increase the risk of allergic diseases, such as allergic rhinitis, asthma, eczema, and food allergies, similar to the results of the present study. However, this was diametrically opposed by the findings of Gorris et al. (13, 21, 32, 33), who demonstrated that no significant relationship exists between delivery via cesarean section and the risk of pediatric allergic rhinitis. The effect of delivery via cesarean section on allergic rhinitis has remained controversial in recent years, and the differences might be attributed to insufficient sample sizes, dietary differences, weather differences, and exposure levels, indicating the necessity for further research.

The present study analyzed the association between cesarean section delivery patterns and the risk of pediatric allergic rhinitis after adjusting for confounding factors, such as age, gender, birth weight, passive smoking, feeding patterns in the first 6 months, maternal educational level, household income, and antibiotic exposure. However, due to lacking raw data, adjusting for confounding factors for maternal diseases during pregnancy and family allergy was infeasible. Mitselou et al. (34) categorized the causes of cesarean section into elective labor and emergency delivery and showed that emergency cesarean section increased the risk of allergic rhinitis more than optional cesarean section after adjusting for confounding factors. Emergency cesarean section was mainly associated with maternal morbidity during pregnancy, and some studies have found that pregnancy-associated complications increased the risk of allergic diseases in children and the risk of intrauterine infection (35). Pistiner et al. (17) analyzed study subjects with and without family history of allergy, and the results showed that in children with family history of allergy, cesarean section increased the incidence of allergic rhinitis. In the present study, the included studies were divided into two groups based on whether they adjusted for factors for family history of allergy or not, and a subgroup analysis was performed. It was found that the risk of pediatric allergic rhinitis in studies that adjusted for factors for family history of allergy was OR: 1.29, 95% CI: 1.13–1.47, which was not significantly different from those studies that did not adjust for factors for family history of allergy (OR: 1.27, 95% CI: 1.19–1.35). This result, contrary to recent studies that demonstrated that family history of allergy had an influence on the risk of pediatric allergic rhinitis (17, 25, 36), is worthy of further assessment using more research to verify whether allergic genetic predisposition can interact with the effects of cesarean section, making allergic rhinitis more likely to occur in children.

In the present study, subgroup analysis was performed on data stratified by region. For this purpose, four subgroups of Asia, Europe, South America, and North America were considered. The results of subgroup analysis revealed that in Asia (OR: 1.29, 95% CI: 1.18–1.41), Europe (OR: 1.13, 95% CI: 1.02–1.25), South America (OR: 1.67, 95% CI: 1.10–2.52), and North America (OR: 1.44, 95% CI: 1.28–1.63), both cesarean delivery methods increased the risk of pediatric allergic rhinitis, while OR indicated a different level of risk. The results showed that the risk of pediatric allergic rhinitis was the highest in South America and the lowest in Europe. ECRHS reports have also shown that the risk of nasal allergies varies by geographical region (37), which may be related to regional climate and topographic differences, dietary structure, degree of industrialization, etc. (35, 38, 39).

Europe is located in the northeastern hemisphere and has rich fishery resources, and fish has become a very important part of the daily diet. South America is located in the western and southern hemispheres, and due to the climatic and environmental conditions, its animal husbandry is more developed, and the local people mainly consume beef products. Fish has a richer vitamin D content than beef. Previous studies have shown that allergic rhinitis is associated with a reduced vitamin D level (38, 40–42), which can speculate that the European’s preference for eating fish has significantly reduced the risk of allergic pediatric rhinitis. Testa et al. (35) have studied a large number of studies and found that these studies had taken numerous factors into account in a large and representative population, provided that a relationship between dietary nutrition and allergic rhinitis, and improved pediatric eating habits may reduce the risk of allergy symptoms. This study revealed that due to the different dietary patterns in different regions of the world, pediatric intake of nutrients differs, which may result in different incidence rates of allergic rhinitis.

South America is located almost between the equator and the Tropic of Capricorn, and its climate is mainly tropical rainforest. Compared with the climate of Europe, the climate of South America is characterized by high temperature, high humidity, and heavy rainfall. Such climatic characteristics have led to differences in mite species and concentrations in different regions, especially in the Andes of Colombia, Peru, and Venezuela, where the prevalence of mites is high (43, 44), and mites are a very important risk factor for allergic rhinitis. Cingi et al. (38) demonstrated that although the overall level of the atopic epidemic did not increase due to climatic factors, climatic changes were related to the variations in the geographical patterns of the atopic epidemic. They also found that the differences in climate between South America and Europe can lead to different effects of cesarean section on the risk of pediatric allergic rhinitis.

The risk of pediatric allergic rhinitis from cesarean section is also associated with the degree of industrialization and development of the region. Chou et al. (12) assessed the risk of cesarean section and allergy in children and found a significantly higher risk than that reported in highly industrialized countries. This finding may be related to specific conditions, and the degree of industrialization of a region mainly affects a country's degree of development, economic level, healthcare level, air pollution (45, 46), etc. These factors may influence the maturity of cesarean section, the level of healthcare during production, etc., in the region, resulting in different risk levels in different regions of the world.

The high level of industry in Europe, combined with robust healthcare, a great climate, and a healthy diet containing vitamin D, may explain why cesarean section in Europe is associated with a lower risk of pediatric allergic rhinitis compared with that in other regions.

To our knowledge, this study is one of the few recent meta-analyses that have studied the relationship between cesarean section and the risk of pediatric allergic rhinitis, and the results were meaningful for both the prevention and selection of delivery methods for pediatric allergic rhinitis. However, the results indicate the necessity of conducting further relevant research. It is noteworthy that the number of relevant studies was limited; thus, additional studies should be performed to clarify the differences in the risk of pediatric allergic rhinitis stratified by region. Moreover, the number of research subjects in the included studies remarkably varied. In the present meta-analysis, the majority of the included studies were cross-sectional studies, and patients had recall biases in their memories, demonstrating the necessity of more cohort studies to supplement the findings. At the same time, it is well known that prophylactic antibiotics are usually used to avoid infection after cesarean section, and antibiotic use also exists after some vaginal births. We found that this detail was not documented in the present study, so this factor may influence our analysis results. We need to conduct a long-term cohort study in the future to observe whether using antibiotics after delivery has a certain influence on the early development and health of children.

In summary, the results of the present meta-analysis suggested that the mode of delivery via cesarean section increased the risk of pediatric allergic rhinitis after adjusting for confounding factors. The results of the subgroup analysis showed that children in high-risk areas were more affected by cesarean section. In contrast, our experimental results did not support the assumption that family history of allergy increased the risk of pediatric allergic rhinitis. The results of this study provide some reference value for pregnant women in choosing their delivery method, especially in high-risk areas. However, the final choice of pregnant women is influenced by many factors, and the final mode of delivery should be combined with individual specific circumstances. Further evidence is required to clarify the relationship between family history of allergy and the risk of pediatric allergic rhinitis. However, the sample size of the present study was not large enough, it was a retrospective study, and the adjustment of confounding factors was insufficient. Thus, additional studies are required to verify the conclusions.