ABSTRACT
Importance
Understanding the epidemiology and cost burden of pediatric‐onset inflammatory bowel disease (PIBD) is crucial for shedding light on its pathogenesis and making medical insurance decisions, particularly for very early‐onset IBD (VEO‐IBD).
Objective
To assess the epidemiology and cost burden of hospitalized PIBD and VEO‐IBD.
Methods
A multicenter study identified hospitalized PIBD patients aged 0–18 years using the FUTang Updating medical REcords database from 28 hospitals in mainland China (2016–2021). Sociodemographic, clinical characteristics, length of stay (LOS), and expense data were analyzed. The cost burden was evaluated by dividing annual out‐of‐pocket expenditure by household disposable income. Clinical epidemiology and cost burden were compared between Crohn's disease (CD), ulcerative colitis (UC), IBD‐unclassified (IBD‐U), and different age groups.
Results
A total of 5230 hospitalized cases of PIBD were identified. Mean ages for CD (11.8 ± 3.9 years) and UC (8.0 ± 5.2 years) were significantly higher than those of patients with IBD‐U (4.5 ± 4.1 years). Hospitalizations for CD showed a notable annual increase. Patients with CD had a shorter LOS (median 3 days) than those with UC (median 6 days) and IBD‐U (median 7 days). The number of VEO‐CD hospitalizations increased, while that of VEO‐UC declined (2016–2021). The median total hospitalization expenses were $1006.7 for CD and $841.6 for UC. The average proportion of annual cost burden of IBD for each PIBD patient from 2016 to 2021 was 16.47%, 14.34%, 20.55%, 18.45%, 12.13%, and 11.16%, respectively, which has declined significantly since 2020.
Interpretation
This study provides insight into the clinical characteristics and cost burden of PIBD and VEO‐IBD in China. Hospitalizations for PIBD, particularly for CD, are increasing. Guidelines and health insurance policies can help mitigate this cost burden.
Keywords: Childhood, China, Cost burden, Epidemiology, Inflammatory bowel disease, Very early‐onset IBD
This study provides insights into the clinical characteristics and cost burden of pediatric‐onset inflammatory bowel disease (PIBD) and very early onset IBD (VEO‐IBD) in China. Hospitalizations for PIBD, particularly Crohn's disease, are increasing. Guidelines and health insurance policies can help mitigate the cost burden.
INTRODUCTION
Chronic diseases are the second most prevalent disease among Chinese children, 1 with inflammatory bowel disease (IBD) progressively becoming a non‐curable chronic condition. 2 The rising global incidence of IBD is set to exert greater pressure on children, their families, and healthcare systems. 3 Understanding the burden of pediatric‐onset IBD (PIBD) is crucial for shedding light on its pathogenesis. Very early‐onset IBD (VEO‐IBD), which was identified as the onset of IBD under the age of 6 years old, appears to be a distinct subset of PIBD with unique epidemiological and phenotypic characteristics including a severe and aggressive course of disease, predominant colonic involvement and a higher incidence of familial IBD. 4 , 5 Recent systematic review indicated that rates of PIBD continue to rise around the world and data are emerging from regions where it was not previously reported. 6 The peak incidence and prevalence of PIBD were 23.1 per 100 000 person‐years and 75.0 per 100 000 person‐years, respectively. A recent global burden of IBD among children and adolescents revealed that the global prevalence and incidence rate of PIBD had been increasing from 1990 to 2019. 7 However, there remains a paucity of epidemiological data on PIBD and VEO‐IBD, especially in developing and newly industrialized Countries.
Therefore, understanding the epidemiology of childhood IBD in China is crucial. However, as a large developing nation, comprehensive data for the entire country is scarce, with existing studies suggesting only a certain incidence, prevalence rates, and hospitalization characteristics. 8 In recent years, there has been a dearth of high‐quality, multi‐center epidemiological research on childhood IBD, particularly a lack of epidemiological and economic data on VEO‐IBD. 9 This absence of data poses a challenge to the formulation and evaluation of relevant policies.
Here, we retrospectively reviewed the epidemiological data and burden of PIBD and VEO‐IBD from 28 provincial and municipal pediatric hospitals in China from January 2016 to December 2021 (File S1). We aimed to comprehensively describe the hospitalization characteristics, clinical and epidemiological profiles, and cost burden of PIBD in China.
METHODS
Ethical approval
This study was designed as a multicenter hospital‐based study. All data used were de‐identified to protect patient privacy and confidentiality. This study was conducted in accordance with the principles of the Declaration of Helsinki. The protocol was approved by the Institutional Review Board of Beijing Children's Hospital, Capital Medical University (approval number: [2023]‐E‐075‐Y), and informed consent was waived. Since this is an observational study, there is no name for the trial register or the clinical trial registration number. The reporting of this study adhered to the REporting of studies Conducted using Observational Routinely collected Health Data statement 10 (File S2 for details).
Data source and setting
All the data were obtained from the front sheet of medical records collected in the FUTang Updating medical REcords (FUTURE) Database. The database was established by the Futang Research Center of Pediatric Development (FRCPD), the first and largest nonprofit social service organization engaged in pediatric research in China, which was initiated by Beijing Children's Hospital, National Centre for Children's Health in 2013. This alliance of children's hospitals embodies the pinnacle of healthcare quality for diagnosing and treating pediatric illnesses in China. Following the principle of sharing, 28 hospitals within the FRCPD network consented to annually upload the front sheet of medical records for discharged patients to the database. More detailed information regarding the FRCPD and FUTURE databases has been published previously. 11 , 12 Briefly, the main steps of quality control of the FUTURE database included de‐identification, coding instruction, and data cleaning, and did not include data linkage. We could identify multiple records of a patient based on automatically generated unique identifiers, sex, ethnicity, and birthplace. Until the time of the research, the database contained a total of 7 647 598 hospitalized cases from 2016 to 2021.
Case identification and ascertainment
To avoid missing patients, we constructed an algorithm using fuzzy string matching to extract all potential patients with IBD from the database. For patients with Crohn's disease (CD), the algorithm was defined as primary diagnosis should include “CD” or “IBD”, together with the corresponding code based on the International Classification of Diseases (10th‐revision, ICD‐10) was K50.x; For ulcerative colitis (UC), the records whose primary diagnostic contained “UC,” or “IBD” and corresponding ICD‐10 code as K51.x were selected; For IBD‐unclassified (IBD‐U), the identified ICD‐10 code was chosen as K52.3. Considering the differences in the writing of diagnoses in different hospital electronic medical records, we cleaned and screened all Chinese diagnoses that matched and complied with the ICD‐10 codes (see details of File S3).
In the second step, two gastroenterologists manually verified the diagnostic codes or texts using computer algorithms. First, a standard and anonymous electronic case report form (eCRF) was constructed to collect information. Senior clinical experts in China reviewed eCRFs. Second, we evaluated the accuracy of this algorithm by randomly selecting approximately 10% of the cases from Beijing Children's Hospital, Henan Children's Hospital, and Baoding Children's Hospital for a thorough chart review. Two local clinical experts were invited to separately judge the eCRFs of potential cases in accordance with expert consensus on the diagnosis and management of PIBD. A final decision was made based on the voting results following deliberation. The effectiveness of each identification algorithm was evaluated by measuring the positive predictive value (PPV). The detailed process for case identification and validation is described in File S3 and File S4.
Age categorizations
According to the latest epidemiology research, 4 , 6 PIBD was categorized as follows: adolescent‐onset (10–<18 years), early‐onset (6–≤10 years), and VEO‐IBD (0–≤6 years). To further understand the clinical characteristics of VEO‐IBD, age was divided into two categories: toddler‐onset (2–≤6 years) and infantile‐onset (≤2 years).
Variables of clinical epidemiology
Sociodemographic, IBD‐related, and outcome variables were extracted from the front sheet of the medical records for each patient. The sociodemographic variables included sex, age, date of birth, ethnicity, and place of residence; the IBD‐related variables included primary diagnosis and corresponding ICD‐10, year of discharge, length of hospital stay (LOS), operation condition, and discharge conditions.
Assessment of hospitalization expenses and cost burden
In this study, the total hospitalization expenses for each visit were divided into four categories: diagnostic tests, drug treatment costs, non‐drug treatment costs, and other expenses. Out‐of‐pocket costs were also calculated.
Regarding the total annual expenditure of a patient, we summarized the total expense of every hospitalization per patient (with the same unique ID, birth date, and name) over the year based on the date of discharge. The annual cost burden of IBD for each patient was calculated according to the summarized annual out‐of‐pocket expenditures of IBD cases divided by household disposable income. Additionally, we collected data regarding the 31 provincial per capita disposable incomes and average household sizes according to data from the National Bureau of Statistics (https://data.stats.gov.cn/index.htm). Annual household disposable income was calculated as follows: annual provincial per capita disposable income multiplied by the average household size (number of people in a household) (3.11, 3.03, 3.00, 2.92, 2.62, and 2,77 members per family from 2016 to 2021 (https://www.ceicdata.com/zh‐hans/china/population‐no‐of‐person‐per‐household/population‐average‐household‐size). (exchange rate: CNY 7.0, USD 1.0).
Statistical analysis
Continuous data are presented as mean ± standard deviation or median (Q1–Q3) based on the normality of the distribution. Categorical data were reported as numbers (percentages). The CD‐to‐UC ratio was calculated as the ratio of the number of hospitalized cases of pediatric CD to the number of hospitalized cases of pediatric UC. The ratios of VEO‐IBD, early‐onset IBD, and adolescent‐onset IBD were also calculated. We used the One‐Way ANOVA or Kruskal‐Wallis non‐parametric test and the χ2 test for categorical variables to compare characteristics between the three subtypes of IBD (CD, UC, and IBD‐U) and the differences in age categorizations (adolescent‐onset, early‐onset, and VEO‐IBD). To explore the characteristic differences between CD and UC, we further used the Wilcoxon's test or χ2 test. We compared the different types of expenses based on diseases and characteristics for PIBD and VEO‐IBD using the Kruskal‐Wallis non‐parametric test.
Statistical significance was set at P < 0.05. All statistical analyses were performed using the JMP software (version 16.0; SAS Institute Inc., Cary, NC, USA).
RESULTS
Distribution of the included hospitalized cases
From 2016 to 2021, a total of 5230 hospitalized cases due to PIBD were identified in the FUTURE database (Figure 1). The five centers with the largest number of cases were Beijing Children's Hospital (n = 1048), Hunan Children's Hospital (n = 943), Nanjing Children's Hospital (n = 825), Shenzhen Children's Hospital (n = 471), and Zhengzhou Children's Hospital (n = 336) (Table S1). The PPV of the algorithms for verification of PIBD cases randomly selected from three hospitals was 92.1% (350/380).
FIGURE 1.
The flowchart of included hospitalized cases due to pediatric‐onset inflammatory bowel disease (PIBD) from the FUTURE database. IBD, inflammatory bowel disease; VEO‐IBD, very early‐onset inflammatory bowel disease; CD, Crohn's disease; UC, ulcerative colitis; IBD‐U, inflammatory bowel disease‐unclassified; FUTURE, FUTang Updating medical REcords.
The mean age of hospitalized cases for PIBD was 10.7 ± 4.6 years. More than 60% of hospitalized patients were male. Han was the major ethnicity in all hospitalizations. From 2016 to 2021, the number of hospital admissions for PIBD has increased annually. The median LOS for total hospitalization for PIBD was 4 days (interquartile range [IQR]: 2–10) days. Only 13.7% of hospitalizations occurred in only 1‐day hospitalized group. More than 90% of the hospitalized patients left the hospital on a doctor's order and did not have a rehospitalization plan within 1 month after discharge (Table 1).
TABLE 1.
The characteristics of hospitalized patients with pediatric‐onset inflammatory bowel disease (PIBD) in China from 2016 to 2021
| Characteristics | Total (n = 5230) | CD (n = 3889) | UC (n = 1250) | IBD‐U (n = 91) | χ2/F/Z | P |
|---|---|---|---|---|---|---|
| Age (years, means ± SD) | 10.7 ± 4.6 | 11.8 ± 3.9 | 8.0 ± 5.2 | 4.5 ± 4.1 | 463.728 | <0.001 |
| Sex, n (%) | 7.167 | 0.028 | ||||
| Male | 3340 (63.9) | 2511 (64.6) | 764 (61.1) | 65 (71.4) | ||
| Female | 1890 (36.1) | 1378 (35.4) | 486 (38.9) | 26 (28.6) | ||
| Ethnicity, n (%) | 94.007 | <0.001 | ||||
| Han | 4981 (95.2) | 3759 (96.7) | 1145 (91.6) | 77 (84.6) | ||
| Hui | 34 (0.6) | 13 (0.3) | 21 (1.7) | 0 (0.0) | ||
| Man | 26 (0.5) | 10 (0.2) | 15 (1.2) | 1 (1.1) | ||
| Miao | 35 (0.7) | 14 (0.4) | 20 (1.6) | 1 (1.1) | ||
| Yi | 9 (0.2) | 2 (0.1) | 7 (0.6) | 0 (0.0) | ||
| Other | 145 (2.8) | 91 (2.3) | 42 (3.3) | 12 (13.2) | ||
| Year of discharge, n (%) | 318.863 | <0.001 | ||||
| 2016 | 352 (6.7) | 183 (4.7) | 155 (12.4) | 18 (19.8) | ||
| 2017 | 439 (8.4) | 242 (6.2) | 187 (15.0) | 14 (15.4) | ||
| 2018 | 584 (11.2) | 392 (10.1) | 186 (14.9) | 13 (14.3) | ||
| 2019 | 803 (15.4) | 579 (14.9) | 208 (16.6) | 17 (18.7) | ||
| 2020 | 1139 (21.8) | 958 (24.6) | 174 (13.9) | 11 (12.1) | ||
| 2021 | 1913 (36.6) | 1535 (39.5) | 340 (27.2) | 18 (19.8) | ||
| Length of stay [days, median (Q1–Q3)] | 4 (2–10) | 3 (2–8) | 6 (3–13) | 7 (4–10) | 312.733 | <0.001 |
| Group of the length of stay [days, n (%)] | 392.254 | <0.001 | ||||
| 1 | 718 (13.7) | 607 (15.6) | 111 (8.9) | 0 | ||
| 2–3 | 1854 (35.4) | 1632 (42.0) | 204 (16.3) | 18 (19.8) | ||
| 4–7 | 1060 (20.3) | 648 (16.7) | 378 (30.2) | 34 (37.3) | ||
| 8–14 | 799 (15.3) | 467 (12.0) | 305 (24.4) | 27 (29.7) | ||
| >14 | 799 (15.3) | 535 (13.7) | 252 (20.2) | 12 (13.2) | ||
| Surgery, n (%) | 3.676 | 0.159 | ||||
| No | 5162 (98.7) | 3843(98.8) | 1228 (98.2) | 91 (100.0) | ||
| Yes | 68 (1.3) | 46 (1.2) | 22 (1.8) | 0 | ||
| Discharge, n (%) | 19.844 | 0.003 | ||||
| Leave the hospital on doctor's order | 4974 (95.1) | 3717 (95.6) | 1171 (93.7) | 86 (94.5) | ||
| Discharged without a doctor's advice | 221 (4.2) | 151 (3.9) | 69 (5.5) | 1 (1.1) | ||
| Transfer to another hospital as directed by the doctor | 16 (0.3) | 11 (0.3) | 4 (0.3) | 1 (1.1) | ||
| Other | 19 (0.4) | 10 (0.3) | 6(0.5) | 3 (3.3) | ||
| Rehospitalization plan within 1 month after discharge, n (%) | 14.010 | <0.001 | ||||
| No | 4821 (92.2) | 3559 (91.5) | 1171 (93.7) | 91 (100.0) | ||
| Yes | 409 (7.8) | 330 (8.5) | 79 (6.3) | 0 |
Abbreviations: CD, Crohn's disease; IBD‐U, inflammatory bowel disease–unclassified; UC, ulcerative colitis.
Comparison of characteristics for pediatric CD, UC, and IBD‐U
Among all hospitalized patients, 74.4% (3889/5230) were CD patients, 23.9% (1250/5230) were UC, and 1.7% (91/5230) were IBD‐U (Table 1). The mean age of hospitalizations for CD and UC was significantly older than that for IBD‐U (11.8 years and 8.0 years, vs. 4.5 years, P < 0.001). The proportion of male hospitalizations among patients with IBD‐U was significantly higher than that in the CD and UC groups (71.4% vs. 64.6% and 61.1%, respectively, P = 0.028). The proportion of Han people in the CD group was significantly greater than that in the UC or IBD‐U groups (96.7% vs. 91.6% and 84.6%, P < 0.001). The hospitalizations' rapid surge trend by year was particularly prominent among CD patients, which increased from 183 hospitalizations in 2016 to 1535 hospitalizations in 2021. Figure 2A shows that the increase in hospitalization for CD was significantly higher than that for UC from 2016 to 2021, and the CD‐to‐UC hospitalization ratio grew from 1.2 in 2016 to a peak of 5.5 in 2020, with a slight decline in 2021. Compared with UC and IBD‐U, the CD group was associated with a shorter LOS (3 [IQR: 2–8] vs. 6 [IQR: 3–13] and 7 [IQR: 4–10], P < 0.0010) and a higher proportion of hospitalized patients for 1‐day hospitalized (15.6% vs. 8.9% and 0, P < 0.001). No significant differences were observed in terms of surgery (P = 0.159). Hospitalizations with CD had worse rehospitalization plans within 1 month after discharge than those with UC or IBD‐U (8.5% vs. 6.3% and 0, P < 0.001).
FIGURE 2.
The number of hospitalized cases, CD‐to‐UC ratio from 2016 to 2021, and the age subgroup composition of pediatric‐onset IBD and its subtype of the disease. (A) The distribution of pediatric‐onset IBD of hospitalized cases; (B) The age subgroup of pediatric‐onset IBD; (C) The distribution for VEO‐IBD of hospitalized cases; (D) The age subgroup composition of VEO‐IBD. CD, Crohn's disease; UC, ulcerative colitis; IBD, inflammatory bowel disease; IBD‐U, inflammatory bowel disease‐unclassfied; VEO‐IBD, very early‐onset inflammatory bowel disease.
Characteristics of PIBD by age categorizations
Comparisons were made among the three age groups according to each disease. The ratio of VEO‐IBD, early‐onset IBD, and adolescent‐onset IBD in total PIBD was 1:0.77:3.76. Figure 2B and Table S2 show that the majority of adolescents in the onset group were hospitalized for CD (2957/3889), which was higher than that of UC (585/1250) and IBD‐U (12/91) (P < 0.001). Hospitalizations of all age subgroups have increased annually since 2018. The younger the age, the longer the hospital stay (P < 0.001) and the higher the proportion of surgery (P < 0.001), which could be seen in the overall PIBD hospitalized cases as well as in UC, CD, and IBD‐U diseases.
We further compared the distribution of hospitalizations for different diseases in the same age subgroup (Table S3). The mean ages of CD were all older than those of UC in three age subgroups of adolescent‐onset IBD, early‐onset IBD, and VEO‐IBD (13.6 years vs. 12.8 years, 8.5 years vs. 8.2 years, and 3.1 years vs. 1.8 years, all P < 0.001). The median LOS for CD was shorter than that for UC in both the adolescent‐onset and early‐onset subgroups (3 [IQR: 2–6] vs. 6 [IQR: 3–13] and 4 [IQR: 2–12.5] vs. 8 [IQR: 3–13], P < 0.001), whereas this difference was not detected in the VEO‐IBD subgroup (7 [IQR: 2–15] vs. 7 [IQR: 4–11], P = 0.472). The operation proportions were similar in both CD and UC among the three age subgroups (P > 0.05).
Epidemiology characteristics of hospitalizations due to VEO‐IBD
There were 946 hospitalized cases of VEO‐IBD, accounting for 18.1% of all hospitalizations. The mean number of age of VEO‐IBD was 2.4 ± 1.8 years. The number of hospitalizations for VEO‐CD has increased, while that for VEO‐UC has decreased from 2016 to 2021. Therefore, the CD‐to‐UC hospitalization ratio in patients with VEO‐IBD increased rapidly (Figure 2C). The characteristics of VEO‐IBD hospitalizations in mainland China based on toddler‐ and infantile‐onset age subgroups and different diseases are shown in Table 2 and Table S4. The toddler‐onset subgroup comprised the majority of CD in VEO‐IBD, while the majority of UC in VEO‐IBD was in the infantile‐onset subgroup (Figure 2D). Compared with toddler‐onset CD, the LOS of infantile‐onset CD was longer (10 [IQR: 6–20] vs. 6 [IQR: 2–14], P < 0.001), whereas the LOS of the infantile‐onset UC group was similar to that of the toddler‐onset UC group (6 [IQR: 4–11] vs. 7 [IQR: 4–12], P = 0.593). The proportion of patients who underwent surgery for infantile‐onset IBD in both the CD and UC groups was higher than that in the toddler‐onset IBD group (4.5% vs. 1.7%, and 4.6% vs. 0.6%, both P < 0.001).
TABLE 2.
The characteristics of hospitalized cases with very early‐onset inflammatory bowel disease (VEO‐IBD) in mainland China based on different age subgroups from 2016 to 2021
| VEO‐IBD | Toddler‐onset IBD | Infantile‐onset IBD | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Characteristics | Total (n = 946) | CD (n = 293) | UC (n = 174) | IBD‐U (n = 30) | χ2/F/Z | P | CD (n = 134) | UC (n = 283) | IBD‐U (n = 32) | χ2/F/Z | P |
| Age (years, means ± SD) | 2.4 ± 1.8 | 4.0 ± 1.1 | 3.9 ± 1.2 | 3.9 ± 1.2 | 2.016 | 0.134 | 0.9 ± 0.6 | 0.7 ± 0.6 | 0.6 ± 0.5 | 10.273 | <0.001 |
| Sex, n (%) | 13.210 | <0.001 | 3.185 | 0.203 | |||||||
| Male | 583 (61.6) | 157 (53.6) | 116 (66.7) | 24 (80.0) | 79 (59.0) | 183 (64.7) | 24 (75.0) | ||||
| Female | 363 (38.4) | 136 (46.4) | 58 (33.3) | 6 (20.0) | 55 (41.0) | 100 (35.3) | 8 (25.0) | ||||
| Ethnicity, n (%) | 20.437 | <0.001 | 11.971 | 0.153 | |||||||
| Han | 869 (91.9) | 276 (94.2) | 150 (86.2) | 26 (86.7) | 124 (92.5) | 267 (94.3) | 26 (81.3) | ||||
| Hui | 12 (1.3) | 2 (0.7) | 6 (3.4) | 0 | 1 (0.7) | 3 (1.1) | 0 | ||||
| Man | 2 (0.2) | 0 | 0 | 0 | 0 | 1 (0.4) | 1 (3.1) | ||||
| Miao | 3 (0.3) | 0 | 2 (1.1) | 1 (3.3) | 0 | 0 | 0 | ||||
| Yi | 6 (0.6) | 0 | 3 (1.7) | 0 | 2 (1.5) | 1 (0.4) | 0 | ||||
| Other | 54 (5.7) | 15 (5.1) | 13 (7.5) | 3 (10.0) | 7 (5.2) | 11 (3.9) | 5 (15.6) | ||||
| Year of discharge, n (%) | 45.599 | <0.001 | 46.254 | <0.001 | |||||||
| 2016 | 149 (15.8) | 13 (4.4) | 28 (16.1) | 7 (23.3) | 22 (16.4) | 72 (25.4) | 8 (25.0) | ||||
| 2017 | 200 (21.2) | 34 (11.6) | 41 (23.6) | 5 (16.7) | 23 (17.2) | 91 (32.2) | 6 (18.8) | ||||
| 2018 | 154 (16.3) | 61 (20.8) | 29 (16.7) | 5 (16.7) | 14 (10.4) | 41 (14.5) | 4 (12.5) | ||||
| 2019 | 162 (17.1) | 53 (18.1) | 28 (16.1) | 5 (16.7) | 28 (20.9) | 42 (14.8) | 6 (18.8) | ||||
| 2020 | 133 (14.1) | 65 (22.2) | 27 (15.5) | 3 (10.0) | 13 (9.7) | 22 (7.8) | 3 (9.4) | ||||
| 2021 | 147 (15.6) | 67 (22.9) | 21 (12.1) | 5 (16.7) | 34 (25.4) | 15 (5.3) | 5 (15.6) | ||||
| Length of stay [days, median (Q1–Q3)] | 7 (4–13) | 6 (2–14) | 7 (4–12) | 6 (4–9.25) | 1.798 | 0.407 | 10 (6–20) | 6 (4–11) | 10 (7–15.75) | 19.424 | <0.001 |
| Group of the length of stay [days, n (%)] | 29.466 | <0.001 | 64.652 | <0.001 | |||||||
| 1 | 83 (8.8) | 46 (15.7) | 17 (9.8) | 0 | 17 (12.7) | 3 (1.1) | 0 | ||||
| 2–3 | 133 (14.1) | 66 (22.5) | 24 (13.8) | 6 (20.0) | 7 (5.2) | 30 (10.6) | 0 | ||||
| 4–7 | 277 (29.3) | 54 (18.4) | 52 (29.9) | 14 (46.7) | 24 (17.9) | 124 (43.8) | 9 (28.1) | ||||
| 8–14 | 247 (26.1) | 58 (19.8) | 51 (29.3) | 8 (26.7) | 38 (28.4) | 78 (27.5) | 14 (43.8) | ||||
| >14 | 206 (21.8) | 69 (23.5) | 30 (17.2) | 2 (6.7) | 48 (35.8) | 48 (17.0) | 9 (28.1) | ||||
| Surgery, n (%) | 1.563 | 0.460 | 1.525 | 0.466 | |||||||
| No | 921 (97.4) | 288 (98.3) | 173 (99.4) | 30 (100.0) | 128 (95.5) | 270 (95.4) | 32 (100.0) | ||||
| Yes | 25 (2.6) | 5 (1.7) | 1 (0.6) | 0 | 6 (4.5) | 13 (4.6) | 0 | ||||
| Discharge, n (%) | 9.216 | 0.056 | 27.162 | <0.001 | |||||||
| Leave the hospital on doctor's order | 889 (94.0) | 282 (96.2) | 164 (94.3) | 29 (96.7) | 114 (85.1) | 271 (95.7) | 29 (90.6) | ||||
| Discharged without a doctor's advice | 48 (5.1) | 11 (3.8) | 10 (5.7) | 0 | 18 (13.4) | 9 (3.2) | 0 | ||||
| Transfer to another hospital as directed by the doctor | 2 (0.2) | 0 | 0 | 0 | 1 (0.7) | 0 | 1 (3.1) | ||||
| Other | 7 (0.7) | 0 | 0 | 1 (3.3) | 1 (0.7) | 3 (1.1) | 2 (6.3) | ||||
| Rehospitalization plan within 1 month after discharge, n (%) | 2.275 | 0.321 | 2.069 | 0.355 | |||||||
| No | 899 (95.0) | 273 (93.2) | 164 (94.3) | 30 (100.0) | 127 (94.8) | 273 (96.5) | 32 (100.0) | ||||
| Yes | 47 (5.0) | 20 (6.8) | 10 (5.7) | 0 | 7 (5.2) | 10 (3.5) | 0 | ||||
Abbreviations: CD, Crohn's disease; IBD, inflammatory bowel disease; IBD‐U, inflammatory bowel disease‐unclassified; UC, ulcerative colitis; VEO‐IBD, very early‐onset inflammatory bowel disease.
Hospitalization expenses and cost burden of PIBD and VEO‐IBD
Table 3 and Figure 3 show the hospitalization expenses for PIBD and VEO‐IBD in mainland China from 2016 to 2021. The median total expenses of hospitalization for CD and UC were $1006.7 (IQR: 634.2–1891.7) and $841.6 (IQR: 587.3–1292.1), respectively. The median out‐of‐pocket costs of hospitalization for CD and UC were $473.9 (IQR: 97.6–1127.2) and $227.4 (IQR: 0–607.1), respectively. The total expense of VEO‐IBD was lower than that of overall PIBD (P < 0.001). The median total expenses of hospitalization for VEO‐CD and VEO‐UC were $1141.4 (IQR: 490.3–2606.4) and $913.8 (IQR: 555.8–1490.8), respectively. The cost of drug therapy was the major cost of CD for PIBD $584.2 (IQR: 98.8–923.0), while the diagnostic expenses were the major cost of UC both in PIBD and VEO‐IBD ($347.5 [IQR: 173.0–628.3] and $335.3 [IQR: 184.1–561.7]). This trend was also detected in the different LOS groups (Table S5).
TABLE 3.
The comparison of hospitalization expenses based on diseases for pediatric‐onset inflammatory bowel disease (PIBD) and very early‐onset inflammatory bowel disease (VEO‐IBD) from 2016 to 2021
| Variables | PIBD | VEO‐IBD | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total | CD | UC | IBD‐U | χ2 | P | Total | CD | UC | IBD‐U | χ2 | P | |
| Total hospitalization expense (USD) | 1026.9 (656.3– 1945.1) | 1006.7 (634.2–1891.7) | 841.6 (587.3–1292.1) | 1160.1 (696.4–2157.4) | 30.8 | <0.0001 | 990.5 (542.4– 1940.0) | 1141.4 (490.3– 2606.4) | 913.8 (555.8–1490.8) | 843.0 (584.8– 1507.2) | 8.5 | 0.0140 |
| Out of pocket of total hospital expense (USD) | 452.7 (73.0– 1120.9) | 473.9 (97.6– 1127.2) | 227.4 (0.0– 607.1) | 400.6 (0.0–1167.0) | 26.2 | <0.0001 | 191.2 (0.0– 923.0) | 311.9 (0.0– 1312.9) | 119.5 (0.0– 558.7) | 222.5 (0.0– 631.3) | 23.8 | <0.0001 |
| Diagnostic expense (USD) | 232.1 (66.9– 711.8) | 163.9 (59.7–649.6) | 347.5 (173.0– 628.3) | 393.0 (178.0– 832.5) | 178.4 | <0.0001 | 350.8 (154.9– 775.4) | 452.9 (120.5– 1021.2) | 335.3 (184.1– 561.7) | 236.6 (132.0– 630.6) | 6.5 | 0.0391 |
| Non‐drug therapy expense (USD) | 107.4 (38.6– 362.4) | 59.5 (35.9–309.1) | 195.6 (88.8– 357.5) | 265.5 (95.5– 488.3) | 333.1 | <0.0001 | 243.4 (80.2– 513.5) | 223.3 (59.6– 592.1) | 257.4 (99.9– 477.2) | 203.6 (87.0– 398.2) | 2.1 | 0.3597 |
| Drug therapy expense (USD) | 469.8 (93.9– 889.3) | 584.2 (98.8– 923.0) | 144.2 (70.0– 351.8) | 226.7 (90.7– 655.8) | 107.6 | <0.0001 | 201.9 (77.0– 533.9) | 289.6 (68.6– 751.4) | 170.4 (79.3– 392.9) | 186.1 (80.8– 369.2) | 17.6 | 0.0001 |
| Other categories expense (USD) | 32.1 (5.8– 122.6) | 22.1 (5.4– 98.2) | 62.4 (32.1– 151.8) | 51.5 (21.5– 196.9) | 157.3 | <0.0001 | 43.3 (12.8– 180.3) | 45.1 (7.8– 234.7) | 39.6 (15.0– 130.9) | 72.3 (39.3– 170.1) | 8.9 | 0.0115 |
Data was shown as median (Q1–Q3).
Abbreviations: CD, Crohn's disease; IBD‐U, inflammatory bowel disease–unclassified; PIBD, pediatric‐onset inflammatory bowel disease; UC, ulcerative colitis; VEO‐IBD, very early‐onset inflammatory bowel disease.
FIGURE 3.
The cost of subtypes of (A) pediatric‐onset IBD and (B) VEO‐IBD. CD, Crohn's disease; UC, ulcerative colitis; IBD, inflammatory bowel disease; VEO‐IBD, very early‐onset inflammatory bowel disease; IBD‐U, inflammatory bowel disease–unclassified.
The total hospitalization expenses were significantly different when compared with different genders, years of discharge, area, groups of LOS, and age subgroups both in CD and UC subtypes (Table S6). We further analyzed provincial per capita disposable income (Table S7). Therefore, the average proportion of the annual cost burden of IBD for each PIBD patient from 2016 to 2021 was 16.47%, 14.34%, 20.55%, 18.45%, 12.13%, and 11.16%, respectively, which has declined significantly since 2020.
DISCUSSION
The epidemiology and economic issues of PIBD have received heightened attention in recent years, particularly the characteristics of VEO‐IBD in developing and recently developed countries. 6 , 13 This was the first nationwide hospital‐based study covering six administrative divisions throughout mainland China to supplement evidence from developing countries.
To our knowledge, this study is the first to show that the increase in hospitalized cases of CD was significantly higher than that of UC from 2016 to 2021, and the CD‐to‐UC hospitalization ratio increased from 1.2 in 2016 to a peak of 5.5 in 2020, which contributed to an increasing burden on healthcare systems. From the 2022 global systematic review, 6 the incidence and prevalence of pediatric‐onset CD was higher than that of UC in almost all regions. The data showed that the CD‐to‐UC incidence ratio was approximately 2:1 to 3:1, and the CD‐to‐UC prevalence ratio was approximately 5:1 to 6:1, indicating that CD was much more common than UC in most regions around the world. Additionally, our study indicated that the hospitalizations of VEO‐CD increased, while that of VEO‐UC had decreased from 2016 to 2021. This trend was like the report from Israel. 14 The prevalence of CD in Israel increased among all age subgroups (<6, 6–9, and 10–17), whereas the prevalence of UC decreased among those <6 years but increased among older children (6–9 and 10–17). 14 We found over 60% of the hospitalizations involved male patients and the major ethnicity was of Han ethnicity. Other epidemiological studies in China reached a similar conclusion. 9 The recent surge in the incidence of IBD may be attributed to economic development. This assertion is supported by previous research indicating that the occurrence of IBD follows the industrialization and westernization of society, with its incidence showing a positive correlation with the level of economic advancement. 15 , 16 Some newly industrialized Asian regions have rapidly rising hospitalization rates. 15 , 17 Our findings suggest that, to a certain extent, China has entered the “emergence” phase, which is the second stage of IBD global epidemiological evolution. 18
Compared to the recent Chinese nationwide epidemiology study of IBD, 9 the pattern of subtypes of PIBD in mainland China was different from that of adult‐onset IBD. The role of genetic susceptibility and the interplay between genetics and environment may vary. In a study exploring the interactions between NOD2 mutations and smoking habits, it was found that the impact of the 1007fs single nucleotide polymorphism and cigarette smoking varied across different ages. Specifically, the influence of the 1007fs mutation was most significant in individuals diagnosed at the age of 16 years or younger and diminished with increasing age. 19 Similarly, the overall genetic risk of the disease, as measured by genetic risk scores, was shown to decrease with age, particularly in the case of CD. 20 This shift in genetic risk profiles may partially explain the changing ratio of CD to UC in newly diagnosed patients. Notably, two‐thirds of pediatric cases are diagnosed with CD, whereas in adults, the likelihood of being diagnosed with UC or CD is roughly equal.
It is essential to pinpoint the specific expense drivers in the PIBD population to discern which of these cost factors can be adjusted or managed within groups of patients dealing with chronic and recurrent conditions such as IBD. Our findings suggest that the cost burden began to exhibit a marked reduction in 2020. Drug therapy expense was the main component of the total cost for PIBD, especially for the CD subtype, which is in line with a study based on community patients in 20 European countries plus Israel. 21 The implementation of the expert consensus on the diagnosis and treatment of PIBD released in 2019 22 has significantly promoted the standardized use of biologic drugs, especially infliximab. Furthermore, in 2020, China's national medical insurance system included the cost of biological drugs. The coverage under the medical insurance system includes: second‐line treatment for patients with CD and second‐line treatment for patients with moderate to severe UC. The articulation of this significant health decision has, to a certain extent, reduced the treatment costs for pediatric CD and, to some degree, enhanced the willingness of patients with PIBD to seek diagnosis and treatment. However, the significant increase in hospitalization cases for CD after 2020 underscored the critical role of aligning guidelines with health insurance policies in advancing standardized diagnostic and treatment practices in China, which could enhance the cost‐effectiveness of healthcare services. This study confirmed that affordable policies could be equitable for all patients by adjusting the drivers of the costs.
The employment of extensive hospital‐based data to perform multidimensional epidemiological and economic analyses of PIBD represents a strength of our study. However, this study has some limitations. First, although a detailed multi‐center validation of the IBD identification algorithm was performed, it was not possible to validate every case owing to its feasibility. As the foremost pediatric medical association nationwide, the FRCPD collaboration network ensures a relatively uniform level of diagnostic and treatment capability. Consequently, this initiative can enhance the accuracy of the initial page of medical records at each center to a certain degree. Second, the incidence study cannot proceed solely based on data from the first page of the medical records. Future research should focus on designing population‐based cohorts to delineate the epidemiology of PIBD in various regions and comprehend the impact of evolving environmental risk factors on the incidence of PIBD. Third, the indirect costs, such as transportation and missed work, did not be investigated.
In conclusion, the present study is the first to portray the distribution of clinical characteristics and cost burden for PIBD and VEO‐IBD in China. The progressive increase in hospitalizations for PIBD, especially CD, has been confirmed. The development of good practice guidelines and promotion of health insurance policies can reduce the cost burden.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
Supporting information
Supporting Information
ACKNOWLEDGMENTS
We express special thanks for the contributions of the 28 children's hospitals included in this study in the FRCPD. In addition, Dr. Xiaolu Nie sincerely thanked Mr. Muyao Zou for coming, accompanying her, and giving her the opportunity to become a mother during the process of conceiving this research and writing this article. This article is also in memory of this little prince.
Nie X, Li J, Xu H, Hu F, Ye X, Yu M, et al. Epidemiology and the cost burden of hospitalized pediatric‐onset inflammatory bowel disease in China: A national database study. Pediatr Investig. 2025;9:282–292. 10.1002/ped4.70000
Contributor Information
Jie Wu, Email: wujie@bch.com.cn.
Xiaoxia Peng, Email: pengxiaoxia@bch.com.cn.
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