Prevalence and Epidemiological Characteristics of Endoscopically Proven Reflux Esophagitis in Children in Korea

Gastro-oesophageal reflux disease (GERD) is an esophageal mucosal injury or regurgitation that occurs secondary to abnormal reflux of gastric contents into the esophagus. GERD is common in infants, children, and adolescents [1]. Characteristic specific symptoms include heartburn and acid regurgitation [2], but symptoms in pediatric patients vary with age [3, 4]. Although GERD can be diagnosed by typical history and physical examination findings [5], it is difficult to define due to its extensive heterogeneity.

Pediatric patients with pathologic reflux may be more prone to complications of GERD than those with physiologic GER [3]. Esophagogastroduodenoscopy (EGD) with biopsy is recommended to confirm the diagnosis of reflux esophagitis (RE) and to screen for other upper gastrointestinal (GI) disorders whose symptoms may mimic those of GERD in children [3].

Epidemiologic data has indicated an increased prevalence of RE in recent decades in Asia [6]. Time trend studies in adults have also indicated an increased prevalence in symptom based-GERD and endoscopic RE [7]. These increases may be due to multiple factors, such as Westernized diet and lifestyle [8]. In addition, risk factors include older age, male sex, race, family history, higher socioeconomic status (SES), increased body mass index (BMI), and smoking [9]. While GERD has been amply studied in adults, there is very limited literature on the characteristics and incidence of RE in children. Time trends of endoscopically proven RE in pediatric patients are unclear.

The objective of this study was to identify time trends in the incidence and the influence of risk factors on the prevalence of endoscopically proven RE in children in Korea.

The results of our study demonstrate that the prevalence of endoscopically proven RE in children during a recent 14-year period has significantly increased when divided into two time periods. Our findings correspond with previous data from Korea which show an increase in the prevalence of erosive esophagitis from 5.7% in 1992 to 19.9% in 2008 among children with upper abdominal pain [11, 12, 13]. Our study also reveals significant associations of age and residency with RE.

The prevalence of RE in adults reportedly varies from 14% to 31% [12, 13, 14, 15]. However, the prevalence of pediatric esophagitis is still unclear and there are few data on the prevalence of RE in children. The prevalence rate of endoscopically proven RE in our study throughout the study period was 28.7%, which was higher than previous studies. Gilger et al. [16] reported a 12.4% prevalence of erosive esophagitis in a population of 888 pediatric patients referred to one institution. This difference might be due to several reasons. First, the time period of investigation in the study of Gilger et al. [16] was 1999 to 2002, which was shorter compared to our study. However, our results showed a similar prevalence of 11.8% in the earlier group of patients from 2001 to 2007. Second, Gilger et al. [16] involved a more randomized population based subjects, which produced a lower prevalence rate than the present result.

GERD is a multifactorial disease that is affected by age, BMI, hiatal hernia, lifestyle, and gender [17, 18, 19]. In recent decades, GERD in adults is prevalent and increasing in Western countries and in Asia, which is thought to be caused by multiple factors that include increased gastric acid secretion due to the westernization of dietary habits, decreased Helicobacter pylori infection rate, and increased obesity rate [20, 21]. Unlike adults, risk factors of RE in children are unclear. Of those that are known, risk factors in severe GERD during childhood include neurological disorders, such as spastic quadriplegia and cerebral palsy [22], congenital malformations including esophageal atresia and tracheoesophageal fistula [23], chronic lung disease [24], and extraesophageal disease [25]. Although obesity and overweight have been reported as independent risk factors for GERD and endoscopy-proven esophageal erosions in adult studies [26, 27, 28], it is controversial in the pediatric population. In addition, the previous reported pediatric study showing no significant association between BMI and RE supports the results of our study [29]. The reason behind BMI losing its significance in multivariate analysis while showing a certain degree of significance in univariate analysis could be due to age acting as a confounding variable, considering that a large proportion of adolescents were included in our study. Thus, as we were not able to control and exclude these confounding variables described above, it would be hard to conclude that BMI is not a risk factor.

Our study reported that the risk ratio for RE was found to increase with age, and several studies of adults also showed a stronger association to RE with aging [17, 18, 30]. These results of adults are thought to be related to decreases in esophageal defense mechanisms with aging [31, 32]. However, the linear relationship between aging and RE in children has not yet been investigated. Thus, further detailed research on risk factors of RE including aging is needed in children.

Meanwhile the association between RE and residence location is not well known in pediatrics, while few studies in adults have reported a positive correlation between high SES and urban residency with RE [33, 34]. We were unable to evaluate the SES of subjects according to well-known indices including the Hollingshead index [35]. Thus, we sought to indirectly investigate the SES of subjects by investigation the location of residency, which was divided into two regions; Greater Gangnam area and other regions. The Greater Gangnam area, which is regarded as the most segregated region in Korea for high income and education, consists of three districts (Gangnam-gu, Songpa-gu, and Seocho-gu) [36, 37]. Therefore, we assumed that the Greater Gangnam area may represent high SES in Korea. With the view of RE as a part of psychosomatic disorder, it is conceivable that children living in the Greater Gangnam area can be more exposed to many stressful educational environments than children living in other areas. Accordingly, higher prevalence of RE in Greater Gangnam area may reflect indirect effects of emotional stress on RE as reported in previous studies [38, 39].

The most common indication for endoscopy and symptom of RE was RAP throughout the study period. In previous studies, up to 25% of children and adolescents are reported to have RAP, whereas the most common symptoms of RE in adults are heartburn and regurgitation [1, 40]. In addition, it should be noted that symptoms of RE in children can be various including RAP, unlike adults, which manifests mainly as heartburn.

This retrospective study has several limitations. The study lacked information regarding the use of medications including proton pump inhibitors and antibiotics prior to EGD. As this study investigated children who underwent EGD for indication only, there was a possibility of selection bias towards those with more severe GI symptoms. Therefore there is a chance that those children examined were actually more likely to have endoscopic pathology than children with abdominal pain in whom physicians choose not to perform invasive testing. Moreover, the increased prevalence rate of endoscopically proven RE may be related to overall increases in EGD rates. As previously stated, the inability to evaluate the SES of subjects according to quantitative indices is another limitation.

Despite these limitations, our study included a large population of 3,413 subjects, the largest number of subjects in the pediatric studies to date. It is also notable that this new result of children living in higher socioeconomic areas showing a higher prevalence of RE. In addition, these findings are meaningful as they provide clues regarding the prevalence of RE and risk factors in Korean pediatric patients.

Given the recent increasing trend of RE, fuller understanding of risk factors will be helpful for early detection and treatment to prevent progression of complications like Barrett esophagus.

In conclusion, the prevalence rate of RE in Korean pediatric patients has significantly increased in 2008 to 2014 compared to 2001 to 2007. Older age and residence in the Greater Gangnam region were associated factors of the development of RE. Further studies are required in order to more definitely delineate the development and risk factors for RE in the pediatric population.

Supplementary data can be found with this article online at http://www.pghn.org and at https://doi.org/10.5223/pghn.2017.20.3.160.