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Risc factors and associated disorders of celiac disease
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Celiac disease (CD) is an immune-mediated enteropathy induced by dietary gluten. CD is prevalent in some 1 % of the general population. In recent decades there has been a marked increase in CD prevalence that may be influenced by environmental risk factors.

Aims: The aim of this thesis was to examine possible risk factors for CD and to gain information on associated disorders of CD.

Methods: In study I we used regional cohort-data from ~11,000 children to examine the association between psychological stress in early life and subsequent CD. In studies II-IV we used nationwide histopathology data to identify individuals with CD (i.e. villous atrophy). In study II we linked data on ~29,000 CD patients to the National patient register to examine the risk of hospital admission for influenza. In studies III-IV we linked data on ~11,000 CD patients to several Swedish registries, including the Medical birth register, to examine neonatal risk factors in CD (study III) and the risk of CD in patients with Down syndrome (study IV).

Results: Psychological stress in the first years of life was not associated with subsequent CD. We found a two-fold increased risk of hospital admission for influenza in patients with CD (95 % confidence interval [CI] = 1.6-2.7).While elective cesarean delivery was associated with an increased risk of later CD (adjusted Odds Ratio [OR] = 1.15; 95 % CI = 1.04-1.26), emergency cesarean delivery was not (adjusted OR = 1.02; 95 % CI = 0.92-1.13). Finally, in study IV we found a six-fold increased risk of CD in children with Down syndrome (95 % CI = 5.09-7.43).

Conclusion: This thesis supports the hypothesis that certain environmental risk factors, such as mode of delivery, but possibly not early psychological stress, influence the risk of CD. The increased risk of hospital admission for influenza indicate that individuals with CD may benefit from influenza immunization. The highly increased risk of CD in Down syndrome supports CD screening in Down syndrome patients.

Place, publisher, year, edition, pages
Örebro: Örebro universitet , 2012. , p. 102
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 68
Keywords [en]
Celiac disease, cohort study, Down syndrome, influenza, pediatrics, population-based, pregnancy outcome, psychological stress, registry
National Category
Medical and Health Sciences Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-22136ISBN: 978-91-7668-865-6 (print)OAI: oai:DiVA.org:oru-22136DiVA, id: diva2:510485
Public defence
2012-05-25, Wilandersalen, Universitetssjukhuset i Örebro, Örebro, 13:30 (Swedish)
Opponent
Supervisors
Available from: 2012-03-16 Created: 2012-03-16 Last updated: 2017-10-17Bibliographically approved
List of papers
1. Psychological stress and coeliac disease in childhood: a cohort study
Open this publication in new window or tab >>Psychological stress and coeliac disease in childhood: a cohort study
2010 (English)In: BMC Gastroenterology, E-ISSN 1471-230X, Vol. 10, p. 106-Article in journal (Refereed) Published
Abstract [en]

Background: Psychological stress has previously been associated with several immunological diseases, e. g. inflammatory bowel disease. Through questionnaire data from the ABIS study (All Babies In southeast Sweden) we examined the association between psychological stress in the family and biopsy-proven coeliac disease (CD) in the child. Methods: We used serious life event, parenting stress, and parental worries as measures of psychological stress. Data were collected when the child was 1 and 2.5 years old in some 11,000 and 8,800 children, respectively. CD was confirmed through small intestinal biopsy (with villous atrophy), and the diagnosis was validated through patient chart data. Results: Serious life event in the family in the child's first 1 or 2.5 years after childbirth was not associated with future CD in the child (Odds Ratio (OR) = 0.45; 95% Confidence Interval (CI) = 0.01-2.65; P = 0.72; and OR = 1.21; 95% CI = 0.43-3.05; P = 0.64, respectively). Neither did we see any association between CD and parenting stress at age 1 year and at 2.5 years (OR = 0.40; 95% CI = 0.01-2.38; P = 0.73 and OR = 0.74; 95% CI = 0.01-4.56; P = 1.00, respectively). Among children exposed to parental worries at 2.5 years, no child had a diagnosis of CD before end of follow-up, compared to 25/8082 (0.3%) among non-exposed children (OR = 0.00; 95% CI = 0.00-2.34; P = 0.64). There was no association between the combined measures of stress and CD. Conclusion: This study found no association between psychological stress and later development of CD in Swedish children. However, we cannot rule out that the lack of such an association is due to limited statistical power.

National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-18906 (URN)10.1186/1471-230X-10-106 (DOI)000282779000002 ()
Available from: 2011-10-04 Created: 2011-09-30 Last updated: 2024-07-04Bibliographically approved
2. Increased risk of hospital admission for influenza in patients with celiac disease: a nationwide cohort study in Sweden
Open this publication in new window or tab >>Increased risk of hospital admission for influenza in patients with celiac disease: a nationwide cohort study in Sweden
2010 (English)In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 105, no 11, p. 2465-2473Article in journal (Refereed) Published
Abstract [en]

Objectives: Although earlier studies suggest an increased risk of infectious disease in celiac disease (CD), data on the risk of influenza in patients with CD are limited. We examined the risk of hospital admission for influenza in CD patients, but for comparative reasons also in individuals with small-intestinal inflammation or normal mucosa but positive CD serology.

Methods: In 2006-2008, we collected duodenal/jejunal biopsy data on CD (Marsh 3: villous atrophy, VA; n=29,008 unique individuals) and inflammation (Marsh 1-2; n=13,200) from all 28 pathology departments in Sweden. A third regional cohort consisted of 3,709 individuals with positive CD serology but normal mucosa (Marsh 0). The biopsies were performed between 1969 and 2008. Through linkage with the Swedish Hospital Discharge Register, we estimated the risk of hospital admission for influenza compared with that of 224,114 age-and sex-matched controls from the general population.

Results: Individuals with CD were at increased risk of hospital admission for influenza (hazard ratio (HR)=2.1; 95% confidence interval (CI)=1.6-2.7; n=81). The absolute risk of influenza was 30/100,000 person-years (excess risk: 16/100,000 person-years). Furthermore, children with CD were at increased risk of influenza (HR=2.5; 95% CI=1.3-4.8). Whereas individuals with inflammation without VA were also at increased risk of influenza (HR=1.9; 95% CI=1.4-2.5), individuals with normal mucosa but positive CD serology were not (HR=1.2; 95% CI=0.5-3.0).

Conclusions: This study found an increased risk of hospital admission for influenza in patients with CD.

Place, publisher, year, edition, pages
New York, USA: Nature Publishing Group, 2010
National Category
Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-18874 (URN)10.1038/ajg.2010.352 (DOI)000283775600019 ()20823839 (PubMedID)2-s2.0-78149282225 (Scopus ID)
Available from: 2011-10-04 Created: 2011-09-30 Last updated: 2018-04-24Bibliographically approved
3. Pregnancy outcome and risk of celiac disease in offspring: a nationwide case-control study
Open this publication in new window or tab >>Pregnancy outcome and risk of celiac disease in offspring: a nationwide case-control study
Show others...
2012 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 142, no 1, p. 39-45.e3Article in journal, Editorial material (Refereed) Published
Abstract [en]

Background & Aims: Studies on pregnancy characteristics and mode of delivery and risk of later celiac disease in offspring are inconsistent. In recent decades rates of cesarean delivery and preterm birth survival have increased while at the same time the prevalence of celiac disease has doubled.

Methods: In this population-based case-control study we examined the risk of celiac disease in individuals exposed to cesarean delivery and adverse fetal events (ie, low Apgar score, small for gestational age, low birth weight, preterm birth, and neonatal infections). Prospectively recorded pregnancy data were obtained from the Swedish Medical Birth Register between 1973 and 2008. Study participants consisted of 11,749 offspring with biopsy-verified celiac disease identified through histopathology reports from Sweden's 28 pathology departments, and 53,887 age- and sex-matched controls from the general population.

Results: We found a positive association between elective cesarean delivery and later celiac disease (adjusted odds ratio [OR], 1.15; 95% confidence interval [CI], 1.04-1.26), but no increased risk of celiac disease after emergency (adjusted OR, 1.02; 95% CI, 0.92-1.13) or any cesarean delivery (adjusted OR, 1.06; 95% CI, 0.99-1.13). Infants born small for gestational age were at a 21% increased risk of celiac disease (95% CI, 1.09-1.35), whereas other pregnancy exposures did not increase the risk of future celiac disease.

Conclusions: The positive association with elective, but not emergency, cesarean delivery is consistent with the hypothesis that the bacterial flora of the newborn plays a role in the development of celiac disease.

Place, publisher, year, edition, pages
Philadelphia, USA: Saunders Elsevier, 2012
Keywords
Cesarean Section, Prematurity, Register
National Category
Medical and Health Sciences Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-21404 (URN)10.1053/j.gastro.2011.09.047 (DOI)000298250800027 ()21995948 (PubMedID)2-s2.0-83755172194 (Scopus ID)
Note

Funding Agency:

NIDDK NIH HHS DK057892  DK071003  R01 DK057892  R01 DK057892-05  R01 DK071003  R01 DK071003-02  R56 DK071003

Available from: 2012-01-30 Created: 2012-01-30 Last updated: 2018-07-22Bibliographically approved
4. Highly increased risk of celiac disease in individuals with Down syndrome: a nationwide case-control study
Open this publication in new window or tab >>Highly increased risk of celiac disease in individuals with Down syndrome: a nationwide case-control study
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background & Aims: Several studies have indicated a high prevalence of celiac disease (CD) in individuals with Down syndrome (DS), but data from population based studies are lacking.

Methods: In this nationwide Swedish case-control study we examined the risk of CD in individuals with DS born between 1973 and 2008. Study participants consisted of two populations: 11,749 patients with biopsy-verified CD (villous atrophy [VA], equivalent to Marsh III) who were identified through histopathology reports from the 28 pathology departments in Sweden and 53,887 population-based controls matched for sex, age, calendar year of birth and county of residence. We used prospectively recorded data from Swedish health registers to identify individuals with DS. Odds ratios (ORs) were calculated using conditional logistic regression.

Results: Of the 11,749 individuals with CD, 165 had a diagnosis of DS (1.4%) as compared with 55/53,887 controls (0.1%), corresponding to an OR of 6.15 (95% confidence interval [CI] = 5.09-7.43). The association between DS and CD was not affected by maternal age at delivery, infant sex, or presence of type 1 diabetes mellitus in the child.

Conclusions: We found a six-fold increased risk of CD in individuals with DS. This study adds precision to the previously reported association between DS and CD and suggests that patients with DS should undergo screening for CD.

Keywords
population register, risk assessment, screening
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-22742 (URN)
Note

Karl Mårild is also affiliated to Astrid Lindgren Children’s Hospital, Solna, Sweden

J. F. Ludvigsson is also affiliated to Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden

Available from: 2012-05-07 Created: 2012-05-07 Last updated: 2017-10-17Bibliographically approved

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