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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. |
- Stenberg, Reidun, 1954-
(författare)
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Dietary antibodies and gluten related seromarkers in children and young adults with cerebral palsy
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background & Aims: Cerebral palsy (CP), the most common physical disorder in children that affect motor function, is associated with a low weight and height. Celiac disease (CD), an autoimmune disorder precipitated by ingestion of gluten, is another common chronic disease in children that has a negative impact on growth. Based on our findings in a small pilot study, antibodies against gluten, dietary antigens and antibodies against transglutaminase 6(TG6) a new possible gluten related neurological marker have been investigated in an extended group of children with CP. The main aim of this thesis was to find out if the children with elevated gluten related antibodies have enteropathy consistent with CD and if they have antibodies to other dietary antigens as well. We further wanted to study if elevated levels of antibodies were associated to their weight, subtypes of CP and also to investigate if there were an association between the brain damage seen in CP and antibodies against TG6.Methods: Ninety nine children with CP and matched (study4) controls (study3) were analysed for antibodies against gluten, TG6, egg white, lacto-globulin, casein and wheat. Small bowel biopsies were analysed in the majority of the children with antibody positivity, both by routine procedures and by extended analyse (study 2).Results: Significantly elevated levels of gluten related seromarkers and antibodies against casein, lacto globulin and egg white were found in the CP-group compared to matched controls. The overall elevated levels of antibodies were more frequent in the tetraplegic (TP) and dyskinetic (DK) CP -subtypes having the most severe neurologic handicap and undernourishment. Routine and extended small bowel biopsies analysis did not indicate an increased prevalence of CD. Elevated antibodies against TG6 were found in the CP-group and significantly in the tetraplegic CP-subgroup.Conclusion: Children with CP do not have increased prevalence of celiac disease but have elevated levels of gluten related seromarkers as well as antibodies against other dietary proteins compared to matched controls. There was a correlation between underweight, CP-subtypes (TP/DK) and occurrence of the tested antibodies suggesting disturbed intestinal permeability related to underweight. Compared to controls TG6 autoantibodies were found in the TP-subtype of CP that could be a result due to the brain damage.
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