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The multifactorial etiology of celiac disease explored by combining several national registers
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Umeå: Umeå University , 2015. , p. 64
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1749
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Epidemiology; Public health
Identifiers
URN: urn:nbn:se:umu:diva-110003ISBN: 978-91-7601-342-7 (print)OAI: oai:DiVA.org:umu-110003DiVA, id: diva2:860269
Public defence
2015-11-06, sal B, 9 tr, byggnad 1D, Tandläkarhögskolan, Norrlands universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Funder
Swedish Research Council, 80749103Available from: 2015-10-16 Created: 2015-10-12 Last updated: 2018-06-07Bibliographically approved
List of papers
1. Celiac disease risk varies between birth cohorts, generating hypotheses about causality: evidence from 36 years of population-based follow-up
Open this publication in new window or tab >>Celiac disease risk varies between birth cohorts, generating hypotheses about causality: evidence from 36 years of population-based follow-up
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2014 (English)In: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 14, article id 59Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Celiac disease (CD) is a major public health problem with estimated 1-3% prevalence in the general population. In recent years an increase in CD prevalence has been reported both in Sweden and worldwide. This study aimed at examining the annual incidence rate of biopsy-proven celiac disease among children in Sweden over a 36-year period, to assess variations by age, sex and birth cohort, and to assess the clinical impact of these changes.

METHODS: The National Swedish Childhood CD Register was used to identify 9107 children aged 0-14.9 years who were diagnosed with CD during the period 1973 to 2009. From 1973 to 1990 the register covered 15% of the nation, this increased to 40% during 1991-1997; a full national coverage was obtained from 1998 onwards. Estimations for the annual incidence rate, cumulative incidence and clinical impact by age groups, calendar month and birth cohorts were made.

RESULTS: CD incidence is continuing to increase in the child population aged 2-14.9 years. A continued variation in CD incidence was observed in children aged 0-1.9 years, characterized by a marked decrease in most recent years. The median age at diagnosis has increased from 1.0 year in the 1970s to 6.8 years in 2009. The average number of new cases has risen from ~200 during 1973-1983 to ~600 during 2004-2009. In the birth cohorts of 2000-2002 the cumulative incidence even exceeded that of the epidemic cohorts at comparable ages. The highest cumulative incidence was observed in the birth cohorts of 1985-1995 and 2000-2002.

CONCLUSIONS: CD risk varies between birth cohorts, suggesting cyclic environmental and/or lifestyle risk factors in CD etiology. More research on underlying risk factors is required in order to move forward with preventive strategies.

Place, publisher, year, edition, pages
BioMed Central, 2014
Keywords
Celiac disease, Children, Incidence, Epidemiology
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-88851 (URN)10.1186/1471-230X-14-59 (DOI)000334419500001 ()24693975 (PubMedID)
Available from: 2014-05-16 Created: 2014-05-16 Last updated: 2018-06-07Bibliographically approved
2. Neighborhood conditions and celiac disease risk among children in Sweden
Open this publication in new window or tab >>Neighborhood conditions and celiac disease risk among children in Sweden
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2014 (English)In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 42, no 7, p. 572-580Article in journal (Refereed) Published
Abstract [en]

Aim: To investigate celiac disease (CD) clustering at different geographical levels and to examine the association between neighborhood demographic and socioeconomic conditions and the risk of neighborhood CD.

Methods: We included 2080 children diagnosed with CD between 1998 and 2003, identified from 43 of the 47 reporting hospitals in Sweden. A total of 8036 small area market statistics (SAMS) areas were included; these were nested in 253 municipalities that were further nested into eight ‘nomenclature of territorial units for statistics’ (NUTS) 2 regions. We performed multilevel logistic regression analyses.

Results: We found the highest geographical variation in CD incidence at the municipality level, compared to the region level. The probability of having CD increased in the statistical areas of (SAMS) areas with higher average annual work income, with an odds ratio (OR) of 2.24 and 95% CI of 1.76–2.85. Reduced CD risk in neighborhoods was associated with higher average age (OR 0.96; 95% CI 0.95–0.97), higher proportion of residents with a university education (OR 0.98; 95% CI 0.97–0.99), and higher level of industrial and commercial activity (OR 0.59; 95% CI 0.44–0.82). We found no significant association between CD risk and population density, proportion of Nordic to non-Nordic inhabitants, nor share of the population with only a compulsory education.

Conclusions: Neighborhood composition influences CD risk. This is one of the first attempts to identify factors explaining geographical variation in CD.

Place, publisher, year, edition, pages
Sage Publications, 2014
Keywords
Celiac disease,  demographics,  education,  environmental risk factors,  geography,  income,  neighborhoods,  socioeconomic conditions, Sweden
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Epidemiology
Identifiers
urn:nbn:se:umu:diva-95395 (URN)10.1177/1403494814550173 (DOI)000344066600004 ()881251 (Local ID)881251 (Archive number)881251 (OAI)
Available from: 2014-10-28 Created: 2014-10-28 Last updated: 2019-02-15Bibliographically approved
3. Maternal and perinatal conditions and the risk of developing celiac disease during childhood
Open this publication in new window or tab >>Maternal and perinatal conditions and the risk of developing celiac disease during childhood
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2016 (English)In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 16, article id 77Article in journal (Refereed) Published
Abstract [en]

Background: Celiac disease (CD) is increasing worldwide, which might be due to the changing environmental and lifestyle exposures. We aimed to explore how conditions related to maternity, delivery and the neonatal period influence CD onset during childhood.

Methods: Using Sweden’s national registers we had access to information on 1 912 204 children born between 1991 and 2009, 6 596 of whom developed CD before 15 years of age. Logistic regression analyses were performed to determine how CD is associated with maternity, delivery and the neonatal period.

Results: Regardless of sex, a reduction in CD risk was observed in children born to mothers aged ≥35 years (odds ratio [OR] 0.8; 95 % confidence interval [CI] 0.7–0.9) and with high maternal income (OR 0.9; 95 % CI 0.8–0.9). Being a second-born child, however, was positively associated with CD. Among boys, elective caesarean delivery increased the risk of CD (OR 1.2; 95 % CI 1.0–1.4), while maternal overweight (OR 0.9; 95 % CI 0.8-0.9), premature rupture of the membrane (OR 0.4; 95 % CI 0.2–0.8) and low birth weight showed a negative association. Girls had an increased CD risk compared to boys and in girls the risk was increased by repeated maternal urinary tract infections (OR 1.1; 95 % CI 1.0–1.2).

Conclusions: Elective caesarean delivery and repeated maternal urinary tract infections during pregnancy are associated with increased risk of CD onset during childhood, suggesting the role of dysbiosis during early life. High maternal age and high income reduced the risk of CD, which might be due to infant-feeding practices and life style.

Place, publisher, year, edition, pages
BioMed Central, 2016
Keywords
Celiac disease, Caesarean, Children, Delivery, Elective, Income, Infections, Perinatal, Pregnancy, Register
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-110044 (URN)10.1186/s12887-016-0613-y (DOI)000377535900001 ()27267234 (PubMedID)
Available from: 2015-10-14 Created: 2015-10-14 Last updated: 2020-02-28Bibliographically approved
4. Season and region as risk factors for celiac disease: a key to the aetiology?
Open this publication in new window or tab >>Season and region as risk factors for celiac disease: a key to the aetiology?
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2016 (English)In: Archives of Disease in Childhood, ISSN 0003-9888, E-ISSN 1468-2044, p. 1114-1118Article in journal (Refereed) Published
Abstract [en]

Background: Coeliac disease (CD) incidence has increased in recent decades, characterised by variations according to sex, age at diagnosis, year of birth, month of birth and region of birth. Genetic susceptibility and exposure to gluten are the necessary factors in CD aetiology, although several environmental factors are considered.

Methods: A nationwide prospective cohort longitudinal study was conducted consisting of 1 912 204 children aged 0–14.9 years born in Sweden from 1991 to 2009. A total of 6569 children were diagnosed with biopsy-verified CD from 47 paediatric departments. Using Cox regression, we examined the association between CD diagnosis and season of birth, region of birth and year of birth.

Results: Overall, CD risk was higher for children born during spring, summer and autumn as compared with children born during winter: adjusted HR for spring 1.08 (95% CI 1.01 to 1.16), summer 1.10 (95% CI 1.03 to 1.18) and autumn 1.10 (95% CI 1.02 to 1.18). Increased CD risk was highest if born in the south, followed by central Sweden when compared with children born in northern Sweden. Children diagnosed at <2 years had an increased CD risk if born in spring while those diagnosed at 2–14.9 years the risk was increased for summer and autumn births. The birth cohort of 1991–1996 had increased CD risk if born during spring, for the 1997–2002 birth cohort the risk increased for summer and autumn births, while for the birth cohort of 2003–2009 the risk was increased if born during autumn.

Conclusions: Season of birth and region of birth are independently and jointly associated with increased risk of developing CD during the first 15 years of life. Seasonal variation in infectious load is the likely explanation.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2016
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-110045 (URN)10.1136/archdischild-2015-310122 (DOI)000388822900011 ()27528621 (PubMedID)
Funder
Swedish Research Council, 839-2008-7491
Available from: 2015-10-14 Created: 2015-10-14 Last updated: 2019-12-11Bibliographically approved

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