The national multicenter pediatric IBD research project was a retrospective descriptive study of children from birth to 17 years of age with confirmed diagnosis of IBD (CD, UC, IBD-U) from 17 medical centers located mainly in the CR, WR, and ER of the KSA. The diagnosis of CD and UC was confirmed based on clinical, laboratory, imaging, endoscopic, and histopathologic findings in accordance to standard guidelines[18]. All children were diagnosed and managed by gastroenterologists. The CR is represented by the greater Riyadh region, the WR is represented by the Makkah region, including Makkah, Jeddah and Taif cities, and the ER includes Dammam, Al Hasa, Al Khobar, Dhahran, Qatif, and Jubail cities. Two age groups were analyzed; the denominator data of the first group, birth to 14 years of age, were available and were analyzed for incidence and time trend. The second group, which included the whole cohort from birth to 17 years of age, was analyzed for demographics, clinical, and laboratory presentations.

Incidence and time trend were analyzed for the age group from birth to 14 years of age only. This is because, in the KSA, adult gastroenterologists managed most children above 15 years of age and were not part of the national multicenter study. Hence, available data from patients above 15 years could not be analyzed for incidence and time trend; however, they were added to those below 15 years to form a cohort from birth to 17 years suitable for the analysis of demographic, clinical, and laboratory presentation. We used the officially published census reports of the Central Department of Statistics and Information denominators for incidence calculations[19]. To investigate the incidence time trend, the yearly incidence of CD and UC in each region were calculated and compared to each other. In addition to this, the incidence trend was evaluated for each region using two intervals: interval 1 (2003-2007) and interval 2 (2008-2012).

In the cohort of children from birth to 17 years of age, demographic features including gender distribution, family history of IBD, consanguinity, duration of illness, age at diagnosis, and diagnostic delay were analyzed. The clinical presentation and selected laboratory markers of severity were compared between regions. These included the proportion of children presenting with weight loss, abdominal pain, diarrhea, blood in stools, complicated presentation in CD (fistulae, strictures), and pancolitis in UC. Laboratory markers included anemia, low albumin, high erythrocyte sedimentation rate, and high C-reactive protein.

Data were analyzed using Statistical Package for Social Studies (SPSS 22; IBM Corp., New York, NY, United States). Categorical variables were expressed as percentages. Chi square test and Fisher exact test were used for categorical variables. Generalized linear Poisson Regression model was used to assess the changes in the incidence rates of UC and CD cases by adjusting region (CR, WR, and ER) and using time period (2003-2012) as the offset variable. A P < 0.05 was considered statistically significant.

The statistical methods of this study were reviewed by Ahmad H. Al sharqawi, Biostatistician, Investigator Support Unit, Prince Naif Health Research Center, King Saud University, Kingdom of Saudi Arabia.

The study is part of the Multicenter Saudi National Pediatric IBD research project approved by the Institutional Review Board of the College of Medicine (No. 10/2647/IRB), King Saud University, Riyadh, Kingdom of Saudi Arabia.

From January 2003 to December 2012, a total number of 459 IBD cases from birth to 17 years (309 CD, 147 UC, 3 IBD-U) were diagnosed. However, because of small numbers, the IBD-U cases were not included in this analysis. The remaining 456 were distributed according to regions: CR 226 (156 CD, 70 UC), WR 134 (80 CD, 54 UC), and ER 96 (73 CD, 23 UC).

The main demographic comparative features are shown in Table 1, indicating a higher number of males with CD and UC from the CR and ER, respectively. The prevalence of positive family history was lower in children with CD from the ER than from the CR or the WR; however, there was no difference in children with UC between the regions. Consanguinity rate was higher in children with CD and UC from the CR and the ER, respectively. The children diagnosed with CD and UC from the ER were characterized by a shorter duration of symptoms before presentation, younger age at diagnosis, and shorter diagnostic delay compared to those diagnosed in the CR or the WR.

There were 390 children from birth to 14 years of age diagnosed with IBD in the three regions. Fifty-five non-Saudi nationals were excluded from the analysis because of the unavailability of denominator data, while two patients were excluded because of the missing data. The remaining 333 Saudi children constituted the study cohort: The CR 39.6% (132/333), the WR 36.4% (121/333), and the ER 24% (80/333).

Comparison of the annual mean incidence of UC and CD in the three regions is shown in Figures 1, showing an increasing trend in all regions with no significant difference between them. Comparison of the prevalence trends of two periods (2003-2007 and 2008-2012) between regions presented in Table 2 showed a high trend; however, it was not statistically significant.

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Figure 1 Incidence pattern and time trend for ulcerative colitis and Crohn’s disease from 2003 to 2012. A: Incidence pattern and time trend for ulcerative colitis from 2003 to 2012. Although not statistically significant, there is increasing trend in all regions; B: Incidence pattern and time trend for Crohn’s disease from 2003 to 2012. Although not statistically significant, there is increasing trend in all regions.

Clinical presentation in children with CD is shown in Table 3. This indicates that a significantly higher proportion of children presented with abdominal pain (P = 0.005), complications such as fistula or stenosis (P = 0.029), higher anemia (P = 0.003), higher erythrocyte sedimentation rate (P < 0.001), higher C-reactive protein (P < 0.001), less blood in stools (P = 0.048), and lower albumin levels (P = 0.014) in the ER. For children with UC, clinical and laboratory features are presented in Table 4, indicating a significantly higher percentage of children in the WR presented with diarrhea (P = 0.033), whereas a significantly lower percentage of children in the ER presented with pancolitis (P < 0.001), and a higher percentage presented with anemia (P = 0.006).

The most important limitation was the retrospective data collection. As a result of this, we were not able to address more specific markers of severity such as documentation the pediatric activity indices over the course of the illness, use of immuno-suppressants or biological agents, the number of hospitalizations, and the need for surgical interventions; instead, we used indirect clinical and laboratory measures of severity in the three regions.

In this study, the most prominent finding is the severe presentation of CD in the Eastern region of the KSA. Regional exploration of IBD profiles within countries may reveal significant differences, which indicates the need for prospective studies that focus on environmental factors, specifically in the form of dietary lifestyle and microbiota analysis. The result of such studies may increase our understanding of IBD.

Inflammatory bowel disease (IBD) has been reported most commonly in Western populations and rarely in others. Increasing reports from developing countries including the Kingdom of Saudi Arabia (KSA) attracted global interest in the search of factors implicated in the pathogenesis of IBD. The present report, exploring IBD profile in different regions may reveal important regional variations undetectable in global national studies.

Although increasing incidence trend of Pediatric IBD is well known in the KSA, regional variation in culture and lifestyle may be involved in variation of IBD profile. The result may direct further research to clarify the causes of regional variation.

The main objective of this report was to explore regional variations in the profile of pediatric IBD in the KSA. The finding of significantly more severe Crohn’s disease (CD) presentation in children from the Eastern region indicates the need for prospective studies to uncover the causes of this variation from the other regions. The results of such studies may increase our understanding of the pathogenesis of IBD.

Data from a national multicenter study of pediatric IBD were used. The incidence, time trend, and clinical presentation of CD and ulcerative colitis (UC) in the Central, Western, and Eastern regions of the KSA were analyzed, and regional comparison was performed. Poisson regression analysis was used to assess regional incidence and Chi-square test for demographic and clinical parameters. A P < 0.05 was considered significant.

We found increasing incidence trend of pediatric UC and CD in all regions of the KSA. However, comparison with other regions, children with CD from the ER presented with significantly higher prevalence of complications such as fistula or stenosis, higher anemia, erythrocyte sedimentation rate, and C-reactive protein; as well as less blood in stools and lower albumin levels. The causes of this finding of more disease presentation of CD remains to be studied.

In this study, the more severe clinical profile of CD in children from the ER of the KSA is a new finding. We hypothesize that lifestyle and microbiota variation are potential causes. Regional analysis is recommended as it may reveal significant variations undetectable by overall national studies. Prospective studies focusing on environmental factors are needed to search the cause. Identification of factors implicated in the severe clinical presentation in CD may lead to preventive and therapeutic recommendations.

This study revealed significantly more severe clinical presentation of CD in one of the regions (ER) of the KSA. This finding indicates the need for prospective studies to search the causes of this clinical picture.