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- Rosén, Anna, 1975-
(författare)
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Mass screening for celiac disease in 12-year-olds : Finding them and then what?
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Mass screening for celiac disease (CD) as a public health intervention is controversial. Before implementation, a suitable screening strategy should be outlined, and the acceptability of the screening scrutinized. Also, the benefits of early detection and possible negative consequences should be explored and compared. The overall aim of this thesis was to evaluate different strategies for finding 12-year-olds with undiagnosed CD in the general population, and to explore the experiences of those receiving the diagnosis in a mass screening.Methods A school-based CD screening of 12-year-olds was conducted in five study sites across Sweden. Out of 10041 children who were invited, 7208 had a blood sample analyzed for CD-marker tissue transglutaminase of isotype IgA (tTG-IgA) and 7161 for total serum IgA (s-IgA). If the s-IgA value was low, tTG-IgG was also measured. Additional analysis of endomysial antibodies (EMA) was performed if borderline values of tTG were found. In total, 192 had elevated CD-markers, 184 underwent a small intestinal biopsy and 153 eventually had CD diagnosed. Before receiving knowledge about their CD status, children and their parents filled in questionnaires regarding symptoms and CD-associated conditions. Questionnaires were returned by 7054 children (98%) and 6294 parents (88%). Later, all adolescents who had been diagnosed with CD more than one year ago (n=145), and their parents, were invited to a mixed-method follow-up study in which they shared their experiences in questionnaires, written narratives and focus group discussions. In total, we have information on 117 (81%) of these adolescents, either from the adolescents themselves (n=101) and/or from their parent/s (n=125). Data were analyzed using a combination of descriptive and analytical quantitative and qualitative methodologies.Results We found that information on symptoms and CD-associated conditions were poor predictors for finding undiagnosed CD in the study population. Questionnaire-based case-finding by asking for CD-associated symptoms and conditions would have identified 52 cases (38% of all cases) at a cost of blood-sampling 2282 children (37% of the study population). The tTG-IgA test had an excellent diagnostic accuracy with the area under the receiver operating characteristic curve of 0.988. If using the recommended cut-off for tTG-IgA (>5 U/mL) 151 had fulfilled biopsy criteria and 134 CD cases had been identified. The strategy of lowering the cut-off to tTG-IgA>4 U/mL, and adding the EMA analysis in those with tTG-IgA between 2-4 U/mL, identified another 17 cases (a 12% increase) at the cost of performing 32 additional biopsies. Measuring total s-IgA in 7161 children discovered only two additional cases at the cost of performing 5 additional biopsies. The positive predictive value of our screening strategy was 80%. Results from the follow-up study of the screening-detected CD cases illustrated that 54% reported health improvement after initiated treatment, but also that these health benefits had to be balanced against social sacrifices. We also found that although the screening-detected diagnosis was met with surprise and anxiety, the adolescents and their parents were grateful for being made aware of the diagnosis. A majority of parents (92%) welcomed a future screening, but both adolescents and parents suggested that it should be conducted earlier in life.Conclusion Obtaining information on symptoms and CD-associated conditions was not a useful step in finding undiagnosed CD cases in a general population. The serological marker tTG-IgA, however, had excellent diagnostic accuracy also when lowering the cut-off. The diagnosis had varying impact on adolescents’ quality of life, and their perceived change in health had to be balanced against the social sacrifices resulting from the diagnosis. Overall, CD mass screening seemed acceptable to most of those who were diagnosed and their parents.
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| 2. |
- Myléus, Anna, 1978-
(författare)
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Towards explaining the Swedish epidemic of celiac disease : an epidemiological approach
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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