Inflammatory bowel disease (IBD) refers to a group of diseases, of which Crohn disease (CD) and ulcerative colitis (UC) are the 2 main types. IBD is ranked among the 5 most prevalent gastrointestinal diseases in the United States, with health care costs exceeding $1.7 billion annually (1) (2–5) (2,6–9) (10) (11–14)
It has been suggested that the incidence and prevalence of both CD and UC have increased recently, especially in industrialized countries, among adults and children (9,15–19)
PATIENTS AND METHODS
Design and Geographical Location
A retrospective epidemiological investigation was conducted to identify a cohort of children diagnosed with IBD and registered in the IBD center at Texas Children's Hospital (TCH) (6) (20,21)
Data Collection
The data used for the present study included children with confirmed diagnosis of IBD and retrieved from the local IBD registry. The data were examined and a procedure manual was created for all of the study variables, including the year of diagnosis, age at diagnosis, race/ethnicity, date of initial diagnosis, and subtype of IBD.
Study Subjects
A cohort of children was studied from the period 1991 to 2002. Cases were identified through a computer program that generated the database for the studied cohort. IBD diagnoses were based on clinical, radiological, endoscopic, and histological criteria (22,23) (22,23)
The distribution of the new onset of IBD cases were identified based on the zipcodes of the patient's residence when the first diagnosis was made. New cases of IBD that were referred from other states were excluded for the analysis. Each case was considered only once during the overall period.
The registry was in compliance with the Health Insurance Portability and Accountability Act. Informed consent and assent were obtained from parents and patients before entering information into the registry. The IBD registry obtained institutional review board approval for the protocol.
Statistical Analysis and Census Data
The study time was aggregated into 2 periods: from 1991 to 1996 and from 1997 to 2002 to increase the sample size within each period and to allow the examination of the changing pattern of the incidence rate for the entire 12 years. Incidence rate was calculated per 100,000 pediatric populations per year using the census data for the 10 counties included in the greater Houston metropolitan area (20,21)
Because information about the exact timing of the IBD onset of each child was difficult to predict, assumptions were made for calculating the denominator. For the census data in 1990 and 2000, the total pediatric population (0–17 years old) was 1,086,988 and 1,367,993, respectively, and accordingly there were 1,227,491 person-years. The total number of boys was 556,156 for the 1990 census and 700,837 for the 2000 census and for girls was 530,832 for the 1990 census and 667,156 for the 2000 census. Race/ethnicity was examined for the 3 major race/ethnic groups: whites, African Americans, and Hispanics. The distribution of the numbers based on the census data is shown in Figure 1 (22) t tests and χ 2 tests were used to examine the effect of age group, sex, and race/ethnicity on the incidence rate for the total study period and for each study period. Because the age of distribution was skewed, the Kolmogorov–Smirnov test was applied to compare the age of diagnosis.
FIGURE 1: The racial/ethnic distribution of IBD cases during the 2 study periods and the racial/ethnic distribution of the greater Houston metropolitan population based on race/ethnicity for the same age group of the studied cases (0–17 years old). IBD = inflammatory bowel disease.
Because of the possible correlation between the study variables of age, sex, study period, and/or race/ethnicity, we applied multivariate analysis using 5% significance level for each disease type to adjust for confounding factors and avoid biased parameter estimates. The 2 study periods were forced into models.
RESULTS
Population Characteristics and IBD Among the 272 Children (1991–2002)
A total of 272 children with first diagnosis of IBD were eligible for the analysis: 56% with CD, 22% with UC, and 22% with IC (Table 1 ). The overall ratio of male-to-female children was 1.2:1 in CD, 0.6:1 in UC, and 0.8:1 in IC. The highest age-related occurrence for CD and UC was found among the 10- to 14-year-old age group. The median age at diagnosis was 12 years for patients with CD and 11 years for patients with both UC and IC. The diagnosis was most common after 10 years of age for both CD and UC; however, a total of 69 children (25% of all of the cases) were diagnosed before the age of 10 years.
TABLE 1: Age, race, and sex distribution of the 272 studied children diagnosed with IBD (1991–2002)
The Changing Pattern of Incidence Rate of IBD (1991–2002)
The overall incidence rate of IBD doubled between 1991 and 2002; from 1.1 of 100,000/year (95% CI 0.85–1.36) to 2.4 of 1,001,000/year (95% CI 2.10–2.77) and this trend was also valid for CD but not for UC as shown in Figure 2 . However, when multivariate analysis was applied for each disease subtype, the study period holds its significance for both CD and UC, independently.
FIGURE 2: The increase of incidence rate of IBD subtypes during the 12-year study period. The significant increase of the incidence rate was more evident for CD and IC, but not for UC. CD = Crohn disease; IBD = inflammatory bowel disease; IC = indeterminate colitis; UC = ulcerative colitis.
Effect of Race, Sex, and Age on the Incidence Rate of IBD
The increasing pattern of the overall incidence rate persisted among the 3 races and ethnic groups (Table 2 ). The overall incidence rate among white children was significantly higher than African American and Hispanic children (Table 2 ). When we examined the ratio of CD:UC for each separate race/ethnic group, CD was found to be diagnosed more often in the 3 groups; however, African American children predominantly had CD rather than UC (Fig. 3 ).
TABLE 2: Age- and race-specific distribution of the incidence rate of IBD per interval year among the 272 children (1991–2002)
FIGURE 3: The CD:UC ratio among the total study children by race/ethnicity. African American children with IBD were more likely to be diagnosed with CD than with UC. CD = Crohn disease; IBD = inflammatory bowel disease; UC = ulcerative colitis.
No difference was found for the overall incidence of IBD between males and females during the total study period: 1.8/100,000 (95% CI 1.14–2.04) for males and 1.9/100,000 (95% CI 1.62–2.30) for females, but males had a higher incidence rate than females during the second period of the study (Table 2 ). However, the incidence of CD was significantly higher than UC for both males and females. When multivariate analysis was applied, sex was the only variable that was forced out of the final model because of the lack of its significance. The overall incidence rate was the highest in the 10- to 14-year-old group for the 2 study periods. The age-specific incidence increase was observed among each age group, except for the youngest age group (0–4 years), in which the incidence rate was the same for both periods (Table 2 ). Furthermore, the highest incidence of those between 10 to 14 years was consistently observed among both patients with CD and patients with UC (Fig. 4 ).
FIGURE 4: The age-related incidence of IBD in the 2 study periods. In the 1997–2001 period, the overall incidence of IBD was <2/100,000, rising to 5/100,000 by the age of 10 to 14 years. The highest age-related occurrence for IBD was found in the 10- to14-year-old age group. IBD = inflammatory bowel disease.
Because disease type was found to be significant, multivariate models were applied for each disease subtype. Older age group, white race, and the second study period remained highly significant for both CD and UC independently.
DISCUSSION
Several important observations have emerged from the present study. First, the crude incidence rate of IBD in children doubled from 1991 to 2002. Among white children, the incidence rate increased from 1.43/100,000 to 4.15/100,000 during the total study period. These figures are comparable to the incidence rates reported from the Netherlands (24) (25) (26) (9) (15–19) (16) (27) (25) (28)
The second novel finding of the present study is the observed difference in the incidence rates between different ethnic groups because the epidemiology of IBD among minorities in the United States has been underrepresented. Our findings revealed 2- and 3-fold higher rate of IBD among white children compared with African American and Hispanic children, respectively. The reason is still unknown, but IBD is a complex disease that is controlled by multiple risk factors (29) CARD15 mutational frequencies among African American and Hispanic children within the general population are lower than among white children (30) (31) (32–34) (9)
Although CD was diagnosed more than UC among the 3 race/ethnic groups in our study, it was more predominant among African American children diagnosed with IBD. A recent study reported that African American and Hispanic patients with CD, but not patients with UC, had lower prevalence of family history of IBD than their white counterparts, concluding that racial difference may reflect underlying genetic variations (35) (36) (37) (38)
Our results revealed that the highest incidence rate of IBD was observed among the 10- to 14-year-old group for both CD and UC; 20% of the total IBD studied cases were diagnosed before the age of 10 and 4% between ages 0 to 2 years. This observation emphasizes previous reports regarding the diagnosis of IBD among children younger than 10 years of age (14,39)
In contrast with other studies, our present study did not find a sex effect on the incidence of IBD. Studies from the United States and the United Kingdom reported a higher proportion of boys than girls diagnosed with CD (9,16) (40,41)
The use of data for constructing a retrospective cohort has some shortcomings. First, the studied population presented to a tertiary care from a single center and the possibility of missing some new IBD cases exists because there were 2 to 3 private practices in the same area but opened only in 2000. However, TCH is one of the largest children's hospitals in the nation offering a diverse population at large that closely reflects that of the Texas population. Additionally, missing some cases from other practices would not have influenced the validity of our results because it would have only increased the incidence rate by a small margin (the volume of patients seen in TCH is much higher). The second limitation was that a higher proportion of African American and Hispanic children residing in large cities in general and Houston specifically, may be evaluated more in city or public hospitals than in private hospitals. However, the total number of African American and Hispanic children diagnosed with IBD in these public hospitals is small and would not have affected the overall calculation of the incidence rate in our study. Furthermore, some suspected cases of IBD in children in these hospitals are referred to TCH for further evaluation. The third limitation is the small number of Hispanic children during the first study period, which limited the power to examine whether race/ethnicity is a major risk factor for the IBD etiology. Nevertheless, our total sample size was large enough to allow the examination of age-, sex-, and race-related difference in the 3 subtypes of IBD. A final limitation was that this study was not able to examine the effect of other races because of the small sample size in the IBD registry.
In conclusion, this study demonstrates clear evidence for the rising incidence of IBD among children in the United States that was clearer for CD than UC. The findings imply that the clinical field of childhood IBD is evolving and that the disease affects all ages, boys and girls, and all races/ethnicities. Recognition of these results will have important implications for diagnosis and management of inflammatory bowel disease in children.
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