Journal of Pediatric Gastroenterology & Nutrition:
Original Articles: Gastroenterology
Burden of Illness and Use of Health Care Services Before and After Celiac Disease Diagnosis in Children
Mattila, Eeva*; Kurppa, Kalle†; Ukkola, Anniina*; Collin, Pekka‡; Huhtala, Heini§; Forma, Leena§; Lähdeaho, Marja-Leena†; Kekkonen, Leila||; Mäki, Markku†; Kaukinen, Katri¶
*School of Medicine, University of Tampere
†Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital
‡Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital
§School of Health Sciences, University of Tampere
||Finnish Celiac Society
¶Departments of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital and Internal Medicine, Seinäjoki Central Hospital and School of Medicine, University of Tampere, Tampere, Finland.
Address correspondence and reprint requests to Katri Kaukinen, MD, PhD, University of Tampere, School of Medicine, FIN-33014 Tampere, Finland (e-mail: firstname.lastname@example.org).
Received 13 December, 2012
Accepted 23 February, 2013
www.clinicaltrials.gov registration number: NCT01145287.
This study was financially supported by the Academy of Finland Research Council for Health, the Finnish Medical Foundation, the Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital, the Mary and Georg C. Ehrnrooth Foundation, the Foundation for Pediatric Research, the Maud Kuistila Foundation and the Sigrid Juselius Foundation.
The authors report no conflicts of interest.
Objectives: Prevalence of celiac disease in children is approximately 1%, but most patients remain unrecognized by reason of variable clinical presentation. Undetected patients may have an increased burden of illness and use of health care services because of nonspecific complaints. We investigated these issues prospectively in newly detected patients with celiac disease before and after diagnosis in a large nationwide cohort of children.
Methods: A validated questionnaire was sent to consecutive families whose children had been diagnosed as having celiac disease within 1 year. The survey contained questions about the use of medical consultations, on-demand drugs, vitamins and herbal products, children's absenteeism from day care or school and, parents’ work absenteeism. A follow-up questionnaire was sent after 1 year of receiving a gluten-free diet.
Results: A total of 132 families responded. A total of 44 children were diagnosed because of gastrointestinal and 88 because of extraintestinal symptoms or by risk-group screening. On treatment, outpatient visits to primary health care decreased from a mean of 3.0 to 1.3 visits per year (P < 0.001), the number of hospitalizations from 0.2 to 0.1 (P = 0.008), and antibiotic prescriptions from 1.0 to 0.5/year (P < 0.001). Visits to secondary and tertiary health care increased from 0.6 to 1.4 (P < 0.001), mostly for celiac surveillance. Use of vitamins, micronutrients, and herbal products increased from 7.3 to 10.2 pills per month (P = 0.028).
Conclusions: Implementation of a gluten-free diet resulted in reduced use of health care services and antibiotic prescriptions in children. Our findings support active case-finding and risk-group screening for celiac disease.
Celiac disease is a lifelong gluten-induced disease, affecting approximately 1% of the pediatric population in Western countries (1–3). The condition can manifest itself with a variety of intestinal and extraintestinal symptoms or even be asymptomatic (4–6). Because of the nonspecificity of the symptoms, there is often a long delay in diagnosis (7–12), and the condition may even remain undiagnosed (1,13,14). Unrecognized celiac disease may predispose to complications such as short stature or osteoporotic fractures and cause an incremental burden to the health care system (8,15–17). As long as the diagnosis remains unsettled, families may repeatedly seek help for their children's vague and nonspecific symptoms (9–12), which could be seen as an excessive use of medical services. These children may even be treated with painkillers and unnecessary antibiotics. Untreated illness may also possibly lead to children's day care or school absenteeism or parents’ absence from work. In adults it has been shown that untreated celiac disease incurs significant economic burden, especially on account of incremental outpatient visits (18,19); in children evidence on this issue is scant (8).
We sought to establish whether untreated celiac disease involves an incremental utilization of health care services, use of on-demand medicines and children's absenteeism from school or day care and parents’ absenteeism from work. These self-reported issues were compared retrospectively 1 year before and prospectively 1 year after the diagnosis of celiac disease in a nationwide cohort of children.
Patients and Study Design
The study was conducted at the University of Tampere and Tampere University Hospital. Data were obtained by a nationwide postal survey implemented in collaboration with the Finnish Celiac Society, which presently has >20,000 members. Based on previous information from the Society and study by Virta et al, we estimated that approximately 70% of patients with celiac disease are members of the Society (20,21). Members of the Society younger than 16 years or their parents were invited between February 2007 and May 2008 to participate and received a structured and validated questionnaire. Only biopsy-proven patients with celiac disease diagnosed within 1 year were included. A follow-up questionnaire was sent to all of the original respondents after 1 year receiving a gluten-free diet. All of the data were blindly coded before analysis. Written consent was obtained from all of the study patients and their parents after a full written explanation of the aims of the study, including considerations regarding ethics and data protection and the anonymous deposition of the questionnaires.
The baseline questionnaire comprised inquiries into sociodemographic data, the clinical features of celiac disease at diagnosis, the duration and severity of the symptoms, and medical consultations before diagnosis. Use of health care services, including inpatient and outpatient visits per year and self-reported consumption of pharmaceutical agents such as antibiotics per year and painkillers, probiotics, vitamins, micronutrients, and herbal products per month were both asked retrospectively, covering the year previous to the diagnosis and prospectively after 1 year receiving a gluten-free diet. We also inquired whether inpatient visits were related to celiac disease. In addition, children's absence from school or day care during the previous year and parents’ absence from work because of the child's sickness were queried. The appropriateness of the study questions together with the face and content validity of the tested items were pretested by a group of celiac disease members of the Society as previously described in detail (12,22). In brief, test-retest reliability was established using an intraclass correlation coefficient. For the key items measured, the κ values for test-retest reliability ranged from 0.84 to 1.00 (values >0.70 being regarded as excellent). Because the items inquired in the questionnaire were separated, a Cronbach α was not calculated. The face and content validities of the initial items were ensured through evaluation of the survey content by both gastroenterologists and a celiac disease focus group (12).
All of the statistical data were analyzed by PASW for Windows statistical software package version 18.0 (SPSS Inc, Chicago, IL). All testing was 2-sided and P < 0.05 was considered statistically significant. Nonparametric Wilcoxon signed rank test was used to compare changes within the study group; however, to make the results more comprehensive, mean values instead of medians and quartiles are shown in the tables. In addition, girls and boys were evaluated separately, and significant differences are shown in the results.
The questionnaires were mailed to 222 families, 144 (65%) of whom responded. The final number of participants was 132 after exclusion of 8 children who had been diagnosed >1 year before receiving the questionnaire and 4 who did not have biopsy-proven celiac disease (Table 1). All but 2 families (98%) also responded to the follow-up survey. The median age of the children was 8 years. Forty-four children were diagnosed on the basis of gastrointestinal and 45 extraintestinal symptoms; 43 were found by screening in at-risk groups. The median duration of symptoms leading to the diagnosis was 1 year, but 1 of 4 patients had experienced symptoms from 2 to 10 years (Table 1).
The number of outpatient visits to primary health care and hospital admissions decreased significantly after the diagnosis and commencement of a gluten-free diet compared with the year preceding diagnosis (Table 2). One patient required hospital care because of celiac disease; other inpatient visits were unrelated to celiac disease. The number of outpatient visits to secondary and tertiary health care increased on diet; in boys, this was also seen in the use of other medical services (Table 2).
The number of antibiotic prescriptions decreased significantly after 1 year of receiving a gluten-free diet (Table 3). In contrast, there was no change in the use of all on-demand medicines, painkillers, or probiotics. The use of over-the-counter vitamins, micronutrients, and herbal products increased significantly after the diagnosis. There was a trend toward a decrease in children's absence from school or day care, but this was not statistically significant. Parents’ absence from work decreased significantly in the case of girls but not boys (Table 4).
The most important finding in this nationwide prospective study was that the diagnosis of celiac disease and the subsequent initiation of a gluten-free diet significantly reduced the use of primary health care services and use of antibiotic prescriptions among children. Although the burden of undetected celiac disease was concentrated in particular in primary health care, a small decrease in the number of hospitalizations was seen also upon treatment. The reduction in primary health care visits on a gluten-free diet was in line with our earlier observation among adults with celiac disease, in whom primary health care outpatient visits were also significantly reduced after the implementation of the diet (23).
Unfortunately, we were not able to assess in greater detail the reasons for the reduction in hospital admissions on a gluten-free diet, but there is evidence that untreated celiac disease may increase the risk of infections in children (23–26). Consistent with our findings, it has been shown that in adults, the diagnosis of celiac disease and subsequent dietary treatment significantly reduce the costs of hospitalizations and outpatient visits (8,18,19,27). Nonetheless, although statistically significant, the decrease in the number of hospitalizations seen here was rather small and possibly of no major clinical significance. The increased number of visits to secondary and tertiary health care upon diagnosis seen in the present study is mostly explained by the maintenance of regular follow-up in children with celiac disease. In contrast, adult patients with celiac disease are not usually repeatedly checked after the diagnosis, which probably explains why no similar increase in hospital appointments was seen in the adult celiac population (23). Nevertheless, it has also been reported that Swedish women with celiac disease use health care services more than the general population even while in remission (28). Even though the reduction in children's absenteeism from day care or school and parents’ absenteeism from work was not statistically significant except for the latter in the case of girls, there was a trend suggesting that this issue should be investigated further.
The number of antibiotic prescriptions for children was significantly reduced after the commencement of the gluten-free diet. As mentioned, there is evidence to suggest that celiac disease increases the risk of infection (24–26), which could explain the incremental use of antibiotics before treatment. Physicians may also sometimes prescribe antibiotics as an empirical trial for vague and nonspecific symptoms of celiac disease misinterpreted as an infection. This is an important finding in that children in general consume an abundance of antibiotics, and even a small reduction in this could have a beneficial effect on the individual intestinal microbiota and the emerging antibiotic resistance (29,30). Interestingly, when compared with other chronic intestinal diseases, a study by Virta et al (31) showed children with Crohn disease to use more antibiotics before the diagnosis than healthy controls.
In contrast to a previous study conducted in adults (23), here the use of all on-demand medicines among children was not reduced after 1 year of receiving a gluten-free diet. The discrepancy is probably explained by the fact that children in general use fewer on-demand medicines. Somewhat surprisingly, the use of vitamins, micronutrients, and herbal products increased significantly after the diagnosis, even though they are not routinely recommended in clinical practice. This probably reflects parents’ desire to optimize their children's growth and nutritional balance after the diagnosis of celiac disease.
Most of the children here were diagnosed at their first visit to a physician, and the median duration of symptoms before the diagnosis was short, only 1 year. This is in contrast to some previous findings that numerous consultations and several years had been required before the celiac disease diagnosis was established (9,11,32). For example, D’Amico et al (32) reported that it requires a mean of 7.8 health care visits to reach the right diagnosis, whereas Roma et al (9) found the diagnostic delay in children to be an average of 3 years. In recent years, active case finding and screening in at-risk groups have resulted in an increasing diagnostic rate in this country, and presently the prevalence of biopsy-proven celiac disease is as high as 0.7% (21). This demonstrates that diagnostic accuracy in celiac disease can be significantly enhanced, mainly by education and increased awareness of the condition among health care staff (33). Nevertheless, it must be borne in mind that 25% of the children in the present study had experienced unrecognized symptoms from 2 to 10 years, and as many needed a number of visits before the diagnosis was established. The additional costs incurred by diagnostic delay have already been proven in adult studies (8,18,19), and one may expect the same to apply among children.
The major strengths of the present study were its prospective design and nationwide coverage. The high participation rate meant that the data were collected within the short time period of only 1 year. This renders prospective comparisons reliable by eliminating biases caused by changes in antibiotic policy and clinical practices over time. By using self-reported data, we were able to explore all aspects of health care use instead of data captured in a single database. Besides a high number of patients, our series also included a wide variety of different disease phenotypes, including children detected because of extraintestinal symptoms and by screening in at risk-groups. Hence, we believe that the study cohort well represented patients with celiac disease seen in everyday clinical practice (33). A limitation was that the data were based on self-reported information and detailed reasons for hospitalizations were not systematically collected; however, a recall period of 12 months in self-reported use of health care services and pharmaceutical agents has been shown to be reliable (34). The lack of a control group and possible selection bias because of the membership-based patient recruitment were other limitations to the study.
In conclusion, we showed that the detection of celiac disease in children reduces the use of primary health care resources. In addition, there was a significant decrease in antibiotic use after the commencement of the gluten-free diet. The results give further evidence of benefits of the early diagnosis and timely treatment of celiac disease in children.
1. Mäki M, Mustalahti K, Kokkonen J, et al. Prevalence of celiac disease among children in Finland. N Engl J Med 2003; 348:2517–2524.
2. Fasano A, Berti I, Gerarduzzi T, et al. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med 2003; 163:286–292.
3. Hoffenberg EJ, MacKenzie T, Barriga KJ, et al. A prospective study of the incidence of childhood celiac disease. J Pediatr 2003; 143:308–314.
4. Mäki M, Kallonen K, Lähdeaho ML, et al. Changing pattern of childhood coeliac disease in Finland. Acta Paediatr Scand 1988; 77:408–412.
5. Garampazzi A, Rapa A, Mura S, et al. Clinical pattern of celiac disease is still changing. J Pediatr Gastroenterol Nutr 2007; 45:611–614.
6. McGowan KE, Castiglione DA, Butzner JD. The changing face of childhood celiac disease in North America: impact of serological testing. Pediatrics 2009; 124:1572–1578.
7. Hurley JJ, Lee B, Turner JK, et al. Incidence and presentation of reported coeliac disease in Cardiff and the Vale of Glamorgan: the next 10 years. Eur J Gastroenterol Hepatol 2012; 24:482–486.
8. Greco L, Timpone L, Abkari A, et al. Burden of celiac disease in the Mediterranean area. World J Gastroenterol 2011; 17:4971–4978.
9. Roma E, Roubani A, Kolia E, et al. Dietary compliance and life style of children with coeliac disease. J Hum Nutr Diet 2010; 23:176–182.
10. Norström F, Lindholm L, Sandström O, et al. Delay to celiac disease diagnosis and its implications for health-related quality of life. BMC Gastroenterol 2011; 11:118.
11. Rashid M, Cranney A, Zarkadas M, et al. Celiac disease: evaluation of the diagnosis and dietary compliance in Canadian children. Pediatrics 2005; 116:e754–e759.
12. Ukkola A, Mäki M, Kurppa K, et al. Diet improves perception of health and well-being in symptomatic, but not asymptomatic, patients with celiac disease. Clin Gastroenterol Hepatol 2011; 9:118–123.
13. Lohi S, Mustalahti K, Kaukinen K, et al. Increasing prevalence of coeliac disease over time. Aliment Pharmacol Ther 2007; 26:1217–1225.
14. West J, Logan RF, Hill PG, et al. Seroprevalence, correlates, and characteristics of undetected coeliac disease in England. Gut 2003; 52:960–965.
15. Bottaro G, Cataldo F, Rotolo N, et al. The clinical pattern of subclinical/silent celiac disease: an analysis on 1026 consecutive cases. Am J Gastroenterol 1999; 94:691–696.
16. Meazza C, Pagani S, Laarej K, et al. Short stature in children with coeliac disease. Pediatr Endocrinol Rev 2009; 6:457–463.
17. Ludvigsson JF, Michaelsson K, Ekbom A, et al. Coeliac disease and the risk of fractures: a general population-based cohort study. Aliment Pharmacol Ther 2007; 25:273–285.
18. Green PH, Neugut AI, Naiyer AJ, et al. Economic benefits of increased diagnosis of celiac disease in a national managed care population in the United States. J Insur Med 2008; 40:218–228.
19. Long KH, Rubio-Tapia A, Wagie AE, et al. The economics of coeliac disease: a population-based study. Aliment Pharmacol Ther 2010; 32:261–269.
21. Virta LJ, Kaukinen K, Collin P. Incidence and prevalence of diagnosed coeliac disease in Finland: results of effective case finding in adults. Scand J Gastroenterol 2009; 44:933–938.
22. Kinos S, Kurppa K, Ukkola A, et al. Burden of illness in screen-detected celiac disease children and their families: a nationwide prospective study. J Pediatr Gastroenterol Nutr 2012; 55:412–416.
23. Ukkola A, Kurppa K, Collin P, et al. Use of health care services and pharmaceutical agents in coeliac disease: a prospective nationwide study. BMC Gastroenterol 2008; 20:624–628.
24. Thomas HJ, Wotton CJ, Yeates D, et al. Pneumococcal infection in patients with coeliac disease. Eur J Gastroenterol Hepatol 2008; 20:624–628.
25. Ludvigsson JF, Wahlström J, Grunewald J, et al. Coeliac disease and risk of tuberculosis: a population based cohort study. Thorax 2007; 62:23–28.
26. Mårild K, Fredlund H, Ludvigsson JF. Increased risk of hospital admission for influenza in patients with celiac disease: a nationwide cohort study in Sweden. Am J Gastroenterol 2010; 105:2465–2473.
27. Norström F, Sandström O, Lindholm L, et al. A gluten-free diet effectively reduces symptoms and health care consumption in a Swedish celiac disease population. BMC Gastroenterol 2012; 12:125.
28. Roos S, Wilhelmsson S, Hallert C. Swedish women with coeliac disease in remission use more health care services than other women: a controlled study. Scand J Gastroenterol 2011; 46:13–19.
29. McCaig LF, Hughes JM. Trends in antimicrobial drug prescribing among office-based physicians in the United States. JAMA 1995; 273:214–219.
30. McCaig LF, Besser RE, Hughes JM. Antimicrobial drug prescription in ambulatory care settings, United States 1992–2000. Emerg Infect Dis 2003; 9:432–437.
31. Virta L, Auvinen A, Helenius H, et al. Association of repeated exposure to antibiotics with the development of pediatric Crohn's disease: a nationwide, register-based Finnish case-control study. Am J Epidemiol 2012; 175:775–784.
32. D’Amico MA, Holmes J, Stavropoulos SN, et al. Presentation of pediatric celiac disease in the United States: prominent effect of breastfeeding. Clin Pediatr 2005; 44:249–258.
33. Collin P, Huhtala H, Virta L, et al. Diagnosis of celiac disease in clinical practice: physician's alertness to the condition essential. J Clin Gastroenterol 2007; 41:152–156.
34. Longobardi T, Walker JR, Graff LA, et al. Health service utilization in IBD: comparison of self-report and administrative data. BMC Health Serv Res 2011; 11:137.
burden; celiac disease; children; health care; prospective study
© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,
Highlight selected keywords in the article text.
Connect With Us
Visit JPGN.org on your smartphone. Scan this code (QR reader app required) with your phone and be taken directly to the site.