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Towards explaining the Swedish epidemic of celiac disease: an epidemiological approach
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Celiac disease occurs worldwide in approximately 1% of the population, whereof the majority of cases are undiagnosed. Sweden experienced an epidemic (1984-1996) of clinically detected celiac disease in children below 2 years of age, partly attributed to changes in infant feeding. Whether the epidemic constituted a change in disease occurrence and/or a shift in the proportion of diagnosed cases remains unknown. Moreover, the cause of the epidemic is not fully understood.

Objective: To increase the knowledge regarding the occurrence of celiac disease in Sweden, with focus on the epidemic period and thereafter, as well as the etiology of celiac disease in general, by investigating the Swedish epidemic and its potential causes.

Methods: We performed a two-phased cross-sectional multicenter screening study investigating the total prevalence, including both clinically- and screening-detected cases, of celiac disease in 2 birth cohorts of 12-year-olds (n=13 279): 1 of the epidemic period (1993) and 1 of the post-epidemic period (1997). The screening strategy entailed serological markers analyses, with subsequent small intestinal biopsy when values were positive. Diagnosis was ascertained in clinical cases detected prior to screening. Infant feeding practices in the cohorts were ascertained via questionnaires. An ecological approach combined with an incident case-referent study (475 cases, 950 referents) performed during the epidemic were used for investigating environmental- and lifestyle factors other than infant feeding. Exposure information was obtained via register data, a questionnaire, and child health clinic records. All studies utilized the National Swedish Childhood Celiac Disease Register.

Results: The total prevalences of celiac disease were 2.9% and 2.2% for the 1993 and 1997 cohorts, respectively, with 2/3 cases unrecognized prior to screening. Children born in 1997 had a significantly lower celiac disease prevalence compared to those born in 1993 (prevalence ratio, 0.75; 95% confidence interval [CI], 0.60-0.93). The cohorts differed in infant feeding; more specifically in the proportion of infants introduced to dietary gluten in small amounts during ongoing breastfeeding. Of the environmental and lifestyle factors investigated, no additional changes over time coincided with the epidemic. Early vaccinations within the Swedish program were not risk factors for celiac disease. Early infections (≥3 parental-reported episodes) were associated with increased risk for celiac disease (adjusted odds ratio [OR] 1.5; 95% CI, 1.1-2.0), a risk that increased synergistically if, in addition to having ≥3 infectious episodes, the child was introduced to gluten in large amounts, compared to small or medium amounts, after breastfeeding was discontinued (OR 5.6; 95% CI, 3.1-10). Early infections probably made a minor contribution to the Swedish epidemic through the synergistic effect with gluten, which changed concurrently. In total, approximately 48% of the epidemic could be explained by infant feeding and early infections.

Conclusion: Celiac disease is both unexpectedly prevalent and mainly undiagnosed in Swedish children. Although the cause of the epidemic is still not fully understood, the significant difference in prevalence between the 2 cohorts indicates that the epidemic constituted a change in disease occurrence, and importantly, corroborates that celiac disease can be avoided in some children, at least up to 12 years of age. Our findings suggest that infant feeding and early infections, but not early vaccinations, have a causal role in the celiac disease etiology and that the infant feeding practice – gradually introducing gluten-containing foods from 4 months of age, preferably during ongoing breastfeeding – is favorable.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet , 2012. , 94 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1506
Keyword [en]
celiac disease, epidemiology, etiology, infant feeding, infections, prevalence, screening, vaccinations
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Epidemiology
Identifiers
URN: urn:nbn:se:umu:diva-57831ISBN: 978-91-7459-436-2 (print)OAI: oai:DiVA.org:umu-57831DiVA: diva2:545154
Public defence
2012-09-21, Sal B, 9 trappor. Byggnad 1D, Tandläkarhögskolan, Umeå Universitetssjukhus, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2012-08-31 Created: 2012-08-16 Last updated: 2015-04-29Bibliographically approved
List of papers
1. Celiac disease revealed in 3% of Swedish 12-year-olds born during an epidemic
Open this publication in new window or tab >>Celiac disease revealed in 3% of Swedish 12-year-olds born during an epidemic
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2009 (English)In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 49, no 2, 170-176 p.Article in journal (Refereed) Published
Abstract [en]

Objetive: Sweden experienced a marked epidemic of celiac disease between 1984 and 1996 in children younger than 2 years of age, partly explained by changes in infant feeding. The objective of this study was to determine the prevalence of celiac disease in 12-year-olds born during the epidemic (1993), including both symptomatic and screening detected cases.

Patients and methods: All sixth-grade children in participating schools were invited (n = 10,041). Symptomatic and, therefore, previously diagnosed celiac disease cases were ascertained through the National Swedish Childhood Celiac Disease Register and/or medical records. All serum samples were analyzed for antihuman tissue transglutaminase (tTG)-IgA (Celikey), and serum-IgA, and some for tTG-IgG and endomysial antibodies. A small intestinal biopsy was recommended for all children with suspected undiagnosed celiac disease.

Results: Participation was accepted by 7567 families (75%). Previously diagnosed celiac disease was found in 67 children; 8.9/1000 (95% confidence interval [CI] 6.7-11). In another 192 children, a small intestinal biopsy was recommended and was performed in 180. Celiac disease was verified in 145 children, 20/1000 (95% CI 17-23). The total prevalence was 29/1000 (95% CI 25-33).

Conclusions: The celiac disease prevalence of 29/1000 (3%)-with two thirds of cases undiagnosed before screening-is 3-fold higher than the usually suggested prevalence of 1%. When these 12-year-olds were infants, the prevailing feeding practice was to introduce gluten abruptly, often without ongoing breast-feeding, which might have contributed to this unexpectedly high prevalence.

Place, publisher, year, edition, pages
New York: Raven P, 2009
Keyword
Celiac disease, Children, Infant nutrition, Prevalence, Screening
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-25334 (URN)10.1097/MPG.0b013e31818c52cc (DOI)19516192 (PubMedID)
Available from: 2009-08-12 Created: 2009-08-12 Last updated: 2017-12-13Bibliographically approved
2. Reduced prevalence of childhood celiac disease: an effect of changes in infant feeding?
Open this publication in new window or tab >>Reduced prevalence of childhood celiac disease: an effect of changes in infant feeding?
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(English)Manuscript (preprint) (Other academic)
Keyword
celiac disease, prevalence, infant feeding
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Epidemiology; Pediatrics
Identifiers
urn:nbn:se:umu:diva-57801 (URN)
Available from: 2012-08-30 Created: 2012-08-16 Last updated: 2017-06-13Bibliographically approved
3. Early vaccinations are not risk factors for Celiac Disease
Open this publication in new window or tab >>Early vaccinations are not risk factors for Celiac Disease
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2012 (English)In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 130, no 1, E63-E70 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To investigate if changes in the national Swedish vaccination program coincided with changes in the celiac disease (CD) incidence rate in infants (ie, the Swedish CD Epidemic), and to assess the potential association between these vaccinations and CD risk.

METHODS: All studies were based on the National Swedish Childhood Celiac Disease Register. Using an ecological approach, we plotted changes over time in the national vaccination program in the graph displaying CD incidence rate. A population-based incident case-referent study of invited infants was performed. Exposure information was received through a questionnaire and child health clinic records. Vaccines explored were diphtheria/tetanus, pertussis (acellular), polio (inactivated), Haemophilus influenzae type b (conjugated), measles/mumps/rubella, and live attenuated bacillus Calmette-Guerin (BCG) in children with increased tuberculosis risk. Findings were subjected to a birth cohort analysis.

RESULTS: Introduction of pertussis vaccine coincided in time with decreasing CD incidence rates. In the infant case-referent study, however, neither vaccination against pertussis (odds ratio 0.91; 95% confidence interval 0.60-1.4), nor against Haemophilus influenzae type b or measles/mumps/rubella was associated with CD. Coverage for the diphtheria/tetanus and polio vaccines was 99%. BCG was associated with reduced risk for CD (adjusted odds ratio 0.54; 95% confidence interval 0.31-0.94). Discontinuation of general BCG vaccination did not affect the cumulative incidence of CD at age 15 years.

CONCLUSIONS: Early vaccinations within the national Swedish program were not associated with CD risk, nor could changes in the program explain the Swedish epidemic. A protective effect by BCG was suggested, which could be subject to further studies. Pediatrics 2012;130:e63-e70

Keyword
celiac disease, infant, epidemiology, vaccines
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-57651 (URN)10.1542/peds.2011-2806 (DOI)000305905900009 ()
Available from: 2012-08-09 Created: 2012-08-08 Last updated: 2017-12-07Bibliographically approved
4. Early infections are associated with increased risk for celiac disease: an incident case-referent study
Open this publication in new window or tab >>Early infections are associated with increased risk for celiac disease: an incident case-referent study
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2012 (English)In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 12, no 1, 194- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Celiac disease is defined as a 'chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals'. Sweden has experienced an "epidemic" of celiac disease in children below two years of age. Celiac disease etiology is considered multifactorial; however, little is known regarding potential risk- or protecting factors. We present data on the possible association between early infectious episodes and celiac disease, including their possible contribution to the Swedish celiac disease epidemic.

METHODS: A population-based incident case-referent study (475 cases, 950 referents) with exposure information obtained via a questionnaire (including family characteristics, infant feeding, and the child's general health) was performed. Celiac disease cases were diagnosed before two years of age, fulfilling the diagnostic criteria of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. Referents were randomly selected from the national population register after fulfilling matching criteria. The final analyses included 954 children, 373 (79%) cases and 581 (61%) referents, with complete information on main variables of interest in a matched set of one case with one or two referents.

RESULTS: Having three or more parental-reported infectious episodes, regardless of type of infection, during the first six months of life was associated with a significantly increased risk for later celiac disease, and this remained after adjusting for infant feeding and socioeconomic status (odds ratio [OR] 1.5; 95% confidence interval [CI], 1.1-2.0; P=0.014). The celiac disease risk increased synergistically if, in addition to having several infectious episodes, infants were introduced to dietary gluten in large amounts, compared to small or medium amounts, after breastfeeding was discontinued (OR 5.6; 95% CI, 3.1-10; P<0.001).

CONCLUSION: This study suggests that having repeated infectious episodes early in life increases the risk for later celiac disease. In addition, we found a synergistic effect between early infections and daily amount of gluten intake, more pronounced among infants for whom breastfeeding had been discontinued prior to gluten introduction. Regarding contribution to the Swedish celiac disease epidemic, which partly was attributed to concurrent changes in infant feeding, early infections probably made a minor contribution via the synergistic effect with gluten amount.

National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-64524 (URN)10.1186/1471-2431-12-194 (DOI)23249321 (PubMedID)
Available from: 2013-03-08 Created: 2013-01-31 Last updated: 2017-12-06Bibliographically approved

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