| 1. |
- Högberg, Lotta, et al.
(författare)
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Children with screening-detected coeliac disease show increased levels of nitric oxide products in urine
- 2011
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Ingår i: ACTA PAEDIATRICA. - : Blackwell Publishing Ltd. - 0803-5253 .- 1651-2227. ; 100:7, s. 1023-1027
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Increased concentration of nitric oxide (NO) metabolites, nitrite and nitrate, in the urine is a strong indication of ongoing small intestinal inflammation, which is a hallmark of the enteropathy of coeliac disease (CD). It has previously been shown that children with symptomatic, untreated CD have increased levels of NO oxidation products in their urine. The aim of this study was to investigate whether screening-detected, asymptomatic coeliac children display the same urinary nitrite/nitrate pattern. Methods: In a multicenter screening study, serum samples were collected from 7208 12-year-old children without previously diagnosed CD. Sera were analysed for anti-human tissue transglutaminase (tTG) of isotype IgA. Small bowel biopsy was performed in antibody-positive children, yielding 153 new cases of CD. In the screening-detected individuals, the sum of nitrite and nitrate concentrations in the urine was analysed and used as an indicator of NO production. For comparison, 73 children with untreated, symptomatic CD were studied. Results: The nitrite/nitrate levels in children with screening-detected CD and those with untreated symptomatic CD did not differ significantly. Both groups had significantly increased urinary nitrite/nitrate concentrations compared to the children with normal small bowel biopsy (p andlt; 0.001). Conclusion: Children with screening-detected CD have increased production of NO just as children with untreated symptomatic CD. High NO metabolite levels in the urine may indicate a pathogenetic feature of CD and be a marker of major clinical importance.
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| 2. |
- Ivarsson, Anneli, et al.
(författare)
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Prevalence of Childhood Celiac Disease and Changes in Infant Feeding
- 2013
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Ingår i: Pediatrics. - : American Academy of Pediatrics. - 0031-4005 .- 1098-4275. ; 131:3, s. E687-E694
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Between 1984 and 1996, Sweden experienced an "epidemic" of clinical celiac disease in children andlt;2 years of age, attributed partly to changes in infant feeding. Whether infant feeding affects disease occurrence and/or the clinical presentation remains unknown. We investigated and compared the total prevalence of celiac disease in 2 birth cohorts of 12-year-olds and related the findings to each cohorts ascertained infant feeding. less thanbrgreater than less thanbrgreater thanMETHODS: A 2-phase cross-sectional screening study was performed in which 13 279 children from 2 birth cohorts participated: children born during the epidemic (1993) and children born after the epidemic (1997). Previously diagnosed cases were reported and confirmed. Blood samples were analyzed for serological markers and children with positive values were referred for small intestinal biopsy. Infant feeding practices in the cohorts were ascertained via questionnaires. Prevalence comparisons were expressed as prevalence ratios. less thanbrgreater than less thanbrgreater thanRESULTS: The total prevalence of celiac disease was 29 in 1000 and 22 in 1000 for the 1993 and 1997 cohorts, respectively. Children born in 1997 had a significantly lower risk of having celiac disease compared with those born in 1993 (prevalence ratio: 0.75; 95% confidence interval: 0.60-0.93; P = .01). The cohorts differed in infant feeding (specifically, in the proportion of infants introduced to dietary gluten in small amounts during ongoing breastfeeding). less thanbrgreater than less thanbrgreater thanCONCLUSIONS: A significantly reduced prevalence of celiac disease in 12-year-olds indicates an option for disease prevention. Our findings suggest that the present infant feeding recommendation to gradually introduce gluten-containing foods from 4 months of age, preferably during ongoing breastfeeding, is favorable. Pediatrics 2013;131:e687-e694
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| 3. |
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| 4. |
- Myléus, Anna, 1978-, et al.
(författare)
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Celiac disease revealed in 3% of Swedish 12-year-olds born during an epidemic
- 2009
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - New York : Raven P. - 0277-2116 .- 1536-4801. ; 49:2, s. 170-176
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Sandström, Olof, et al.
(författare)
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Five-year follow-up of new cases after a coeliac disease mass screening
- 2022
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Ingår i: Archives of Disease in Childhood. - : BMJ Publishing Group Ltd. - 0003-9888 .- 1468-2044. ; 107:6, s. 596-600
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We previously performed a population-based mass screening of coeliac disease in children aged 12 years in two birth cohorts resulting in 296 seropositive children, of whom 242 were diagnosed with coeliac disease after duodenal biopsies. In this follow-up study, we wanted to identify new cases in the screening population that tested negative-either converting from potential coeliac disease (seropositive but normal duodenal mucosa) or converting from seronegative at screening to diagnosed coeliac disease.METHODS: All seropositive children were invited to a follow-up appointment 5 years after the screening with renewed serological testing and recommended endoscopic investigation if seropositive. Seronegative children in the screening study (n=12 353) were linked to the National Swedish Childhood Coeliac Disease Register to find cases diagnosed in healthcare during the same period.RESULTS: In total, 230 (77%) came to the follow-up appointment, including 34 of 39 with potential coeliac disease. Of these, 11 (32%) had converted to coeliac disease. One new case was found in the National Swedish Childhood Coeliac Disease Register who received the diagnosis through routine screening in children with type 1 diabetes.CONCLUSIONS: There is a high risk of conversion to coeliac disease among those with potential disease. However, a negative screening test was associated with a very low risk for a clinical diagnosis within a follow-up period of 5 years.
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| 6. |
- Webb, Charlotta, et al.
(författare)
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Accuracy in Celiac Disease Diagnostics by Controlling the Small-bowel Biopsy Process
- 2011
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Ingår i: JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION. - : Lippincott, Williams and Wilkins. - 0277-2116 .- 1536-4801. ; 52:5, s. 549-553
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: In a Swedish celiac disease screening study (Exploring the Iceberg of Celiacs in Sweden), we systematically reviewed the clinical diagnostic procedures with the aim to evaluate the diagnostic accuracy and to take advantage of lessons learned for improving diagnostic routines. Materials and Methods: A school-based celiac disease screening study involving 5 Swedish centers, with 10,041 invited 12-year-olds with 7567 consenting participation. All 192 children with elevated serological markers were recommended to undergo small-bowel biopsy, performed and evaluated according to local clinical routines. All of the mucosal specimens were reevaluated by 1 and, when needed, 2 expert pathologists to reach diagnostic consensus. Results: Small-bowel biopsies were performed in 184 children: 130 by endoscopy and 54 by suction capsule. Endoscopic biopsies were inconclusive in 0.6%, compared with 7.4% of biopsies by suction capsule. A patchy enteropathy was found in 9.1%. Reevaluation by the expert pathologist resulted in 6 additional cases with celiac disease and 1 cleared. Sixteen children with normal or inconclusive biopsies, 4 after endoscopy, and 12 after suction capsule were endoscopically rebiopsied, resulting in another 8 cases. The celiac disease prevalence of 30 of 1000 (95% confidence interval 26-34) was not statistically different from that previously reported. Conclusions: The present review revealed the importance of controlling each step of the diagnostic procedure. Several cases would have been missed by relying only on local routines. To improve the quality of childhood celiac disease diagnostics, we recommend multiple endoscopic biopsies from both proximal and distal duodenum and standardized evaluation by a pathologist with good knowledge of celiac disease.
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| 7. |
- Webb, Charlotta, et al.
(författare)
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Celiac disease can be predicted by high levels of anti-tissue transglutaminase antibodies in population-based screening
- 2015
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - : Lippincott Williams & Wilkins. - 0277-2116 .- 1536-4801. ; 60:6, s. 787-791
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate any potential correlation between anti-tissue transglutaminase antibodies of type immunoglobulin A (tTG-IgA) and the degree of gluten induced enteropathy in children participating in a screening study for celiac disease (CD) and to assess to what extent the revised ESPGHAN (European Society for Paediatric Gastroenterology, Hepatology and Nutrition) guidelines cover this group of patients.METHODS: This is a sub-study of a cross-sectional CD screening study, ETICS (Exploring the Iceberg of Celiacs in Sweden), a two-phased study performed during 2005-2006 and 2009-2010. The 13,279 participating children had a blood test obtained and those with positive tTG-IgA were recommended a small intestinal biopsy. The tTG-IgA levels at the time of biopsy were compared with the assessment of the biopsy.RESULTS: There were 267 children included, of whom 230 were diagnosed with CD. Out of all children, 67 children had low tTG-IgA levels (<5 U/mL), whereof 55% had Marsh 3 lesions. All children with tTG-IgA levels exceeding 10 times the upper limit of normal values of 5 U/mL, i.e. 50 U/mL, were diagnosed with CD. Lowering the cut-off to 3 U/mL, all but one child with 30 U/mL got CD diagnosis.CONCLUSION: By adapting the revised ESPGHAN criteria, biopsies could have been omitted in a fourth of all cases. Our results indicate, that the criteria might be useful even on screened children. Further studies are needed to confirm whether the 2012 ESPGHAN guidelines should be revised to also apply to the populations being screened.
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| 8. |
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| 9. |
- Webb, Charlotta, et al.
(författare)
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High adherence to a gluten-free diet in adolescents with screening-detected celiac disease
- 2015
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - : Lippincott Williams & Wilkins. - 0277-2116 .- 1536-4801. ; 60:1, s. 54-59
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate the gluten-free diet (GFD) adherenceafter one year of follow-up in children with screening-detected celiac disease (CD) in a general population. METHODS: A total of 18,325 12 year olds were invited to participate in apopulation-based CD screening (ETICS- Exploring the Iceberg of Celiacs in Sweden), of whom 13,279 participated. In 240 children, CD was detected through elevated anti-tissue transglutaminase antibodies 2 (TG2-IgA) and verified by a small-intestinal biopsy. This sub-study included the 210 children with TG2-IgAevaluated both at the initialbiopsy occasion and at the one-year follow-up. GFD adherence was evaluated by a combination of TG2-IgA measurements and self-reported adherence (n = 193). RESULTS: After one year, 83% (179/210) had normalizedTG2-IgA levels (<5U/mL). Among those who had >50 U/mL at diagnosis,25% (16/63) still had elevated TG2-IgA but for the majority their initial values were more than halved. Most reported a high level ofGFD adherence ('always' 75%(158/193) and 'often' 14%(30/193)), and 75% (145/193) reported always adhereingcombined with normalized TG2-IgA. Although reporting that they were always adherent, 13 (6.7%) had not yet normalized their TG2-IgA levels completely, however, a majority of these initially had the highestTG2-IgA levels. CONCLUSIONS: GFD adherence is high in adolescents with CD detected by screening of the general population of Swedish 12yearolds. Almost all had normalized serology and reported GFD adherenceat the one-year follow-up. However, a few adolescents whoreported GFD adherence still had elevated TG2-IgA levelssuggesting more severe disease and/or non-adherence.
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| 10. |
- Webb, Charlotta
(författare)
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Screening Detected Celiac Disease in Children
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The prevalence of celiac disease (CD) is estimated to be around 1%, but most CD cases are undiagnosed. Sweden experienced an epidemic of clinically detected celiac disease in children younger than 2 years of age, partly due to changes in infant feeding practices, were the amount of gluten and age at introduction was changed. However, it was not clear if the increase in clinically detected children was due to more CD cases being detected due to symptoms and thus previously undiagnosed, or if it was a true change in CD prevalence. In the revised 2012 ESPGHAN criteria for CD diagnosis, a small intestinal biopsy is no longer mandatory in symptomatic patients when the tTG-IgA levels exceeding ten times the upper limit of normal (> 10xULN) in combination with positivity for EMA and HLA- DQ2 and/or DQ8. Biopsy is still recommended in asymptomatic screening detected cases, were symptoms suggestive of CD is the main difference of the approach to the diagnostic process. Recent studies have shown that screening also detects symptomatic cases, whereas many are unaware of symptoms until after starting on the GFD. Furthermore, there are many pitfalls in the diagnostic process, were the choice of biopsy method and the histopathological evaluation have a significant impact on the diagnostic outcome. To use a capsule device to obtain mucosal specimens was previously considered to be gold standard, but the lesions may be patchy and missed if only one mucosal specimen is obtained. In a clinical setting there can be an advantage of using endoscopy due to the ability to take multiple biopsies. The treatment with a gluten-free diet is a life-long challenge and entails social sacrifices, which may effect the adherence. To be a teenager at the time of diagnosis can be a negative factor, alongside with being screening detected. Objectives: To study the total prevalence of clinical and screening detected celiac disease in children born during the Swedish epidemic, and to investigate the effect and accuracy in each step of the diagnostic process to obtain CD diagnosis. Furthermore, to investigate the correlation between the level of the serological markers (tTG-IgA) and the degree of gluten induced enteropathy and applying the revised 2012 ESPGHAN guidelines on screened CD cases. Additionally, to evaluate the adherence to the GFD in adolescents with screening detected CD. Method: We performed a two-phased screening study, ETICS (Exploring the Iceberg of Celiacs In Sweden). A total of 13 279 twelve year old children were investigated, belonging to two different birth cohorts. The first birth cohort was born during the epidemic period in 1993 and the second cohort was born in the post-epidemic period in 1997. The prevalence of clinically detected CD was gathered from the National Swedish Childhood Celiac Disease Register and the total prevalence was estimated together with the ETICS screening study. Screening for CD was conducted by using a serological marker, anti-tissue transglutaminase antibodies (tTG-IgA). The CD diagnosis was confirmed by a small intestinal biopsy using either a suction capsule or endoscopy according to local routine in the study sites. The clinical diagnostic procedure was reviewed by performing endoscopic re-biopsies in children who hade normal or inconclusive primary biopsy. All of the mucosal specimens were re-evaluated by an expert pathologist and when disagreement with the local pathologist, a second expert pathologist re-evaluated the specimens to reach a diagnostic consensus. The correlation between the degree of enteropathy and the level of the serological markers (tTG-IgA) was investigated by comparing the level of tTG-IgA at the time of biopsy to the degree of gluten induced enteropathy. The revised ESPGHAN guidelines for symptomatic CD was hypothetically applied to the screening cases to evaluate if the biopsy could have been omitted. The adherence to the GFD was measured both by the change of tTG-IgA levels after 12 months and by self-reported questionnaires were the response alternatives were; always, often, sometimes and never. Results: The total prevalence of CD in children born 1993 was 2.9%, with two thirds of the cases being unrecognized. Endoscopic biopsies were inconclusive in 0.6% compared to 7.4% of the capsule biopsies and patchy enteropathy was found in 9% of the children who had conclusive fractions from both proximal and distal duodenum. By controlling the diagnostic process several CD cases were found, re-biopsy resulted in 8 new cases and re-evaluation of all mucosal specimens by an expert pathologist, resulted in additional 6 CD cases. In our screened population all cases with tTG-IgA levels exceeding ten times of normal values (> 10xULN) at a cut-off of 5 U/mL got CD diagnosis and all except for one child got CD diagnosis at a cut-off of 3 U/mL, were the majority had Marsh 3 lesions. The adherence was high in the screened population where 83% had tTG-IgA levels <5 U/mL after 12 months on GFD. Most of the children reported to always (75%) or often (14%) be adherent. There where children who reported to always be adherent but the serological markers were not yet normalized after 12 months. All of these children had halved their initial values, whereof the majority (85%) of these children initially had high serological markers >50 U/mL. Conclusions: The prevalence of 3% was unexpectedly high, whereof two thirds were previously unrecognized. This finding underlines the fact that many CD cases remain undiagnosed, but also that the exposure to an unfavourable infant feeding in this birth cohort may have affected the high total prevalence. The accuracy in the diagnostic procedure is dependant on various factors, where biopsy method and the pathological evaluation are crucial in finding the CD cases. The preferable method for biopsies to be recommended is by using endoscopy and to sharpen the diagnostics to perform re-biopsies and/or re-evaluating in normal or inconclusive biopsies. The revised ESPGHAN guidelines for symptomatic cases seems to be applicable even on screening detected cases, due to the correlation between high levels of tTG-IgA and degree of enteropathy in this group. Screening detected children have a high adherence to the treatment with GFD, which can be measured by using self-reported questionnaires in combination with the change of the serological markers.
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