Significant effects of childhood obesity treatment with a web-based component in a randomised controlled study (Web-COP).

AIM: We evaluated the effect on body mass index standard deviation score (BMI-SDS) of a combined treatment (Web-COP) for children with obesity, including a web-based component targeting their parents. METHODS: This randomised controlled trial recruited children 5-12 years of age with obesity (International Obesity Task Force BMI [IOTF-BMI] ≥30 kg/m2 ) from school health care and outpatient paediatric clinics in in Northern Sweden from 1 June 2019 to 21 June 2020. The children were randomised to Web-COP, an intervention with group sessions and a 12-week web-based component, or standard care. The primary outcome was the change in IOTF BMI-SDS after 6 months. RESULTS: In total, 75 children (33 girls), mean age 9.5 years, were randomised, and 65/75 (87%) children and their parents completed the study, 35/39 (90%) in the Web-COP intervention and 30/36 (83%) in the standard care group. BMI-SDS at 6 months was changed from 3.08 to 2.81 in the intervention group compared to an increase from 3.07 to 3.16 in the standard care group, representing a significant difference between groups (p < 0.001). In the intervention group, 14/30 (47%) reduced their BMI-SDS ≥0.25, compared to none in the standard care group. CONCLUSION: The parent-focused intervention significantly improved BMI-SDS in children with obesity as compared to children in standard care.

Is mass screening for coeliac disease a wise use of resources? A health economic evaluation.

BACKGROUND: Living with undiagnosed symptomatic coeliac disease is connected with deteriorated health, and persons with coeliac disease often wait a long time for their diagnosis. A mass screening would lower the delay, but its cost-effectiveness is still unclear. Our aim was to determine the cost-effectiveness of a coeliac disease mass screening at 12 years of age, taking a life course perspective on future benefits and drawbacks. METHODS: The cost-effectiveness was derived as cost per quality-adjusted life-year (QALY) using a Markov model. As a basis for our assumptions, we mainly used information from the Exploring the Iceberg of Celiacs in Sweden (ETICS) study, a school-based screening conducted in 2005/2006 and 2009/2010, where 13,279 12-year-old children participated and 240 were diagnosed with coeliac disease, and a study involving members of the Swedish Coeliac Association with 1031 adult participants. RESULTS: The cost for coeliac disease screening was 40,105 Euro per gained QALY. Sensitivity analyses support screening based on high compliance to a gluten-free diet, rapid progression from symptom-free coeliac disease to coeliac disease with symptoms, long delay from celiac disease with symptoms to diagnosis, and a low QALY score for undiagnosed coeliac disease cases. CONCLUSIONS: A coeliac disease mass screening is cost-effective based on the commonly used threshold of 50,000 Euro per gained QALY. However, this is based on many assumptions, especially regarding the natural history of coeliac disease and the effects on long-term health for individuals with coeliac disease still eating gluten.

Questionnaire showed that Swedish paediatric clinics complied well with the revised European guidelines for diagnosing coeliac disease.

AIM: In 2012, revised criteria for diagnosing childhood coeliac disease were published by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and incorporated into the revised Swedish guidelines the same year. These made it possible, in certain cases, to diagnose coeliac disease without taking small bowel biopsies. This survey assessed the extent to which the new guidelines were implemented by Swedish paediatric clinics two years after their introduction. METHODS: In October 2014, we distributed a paper questionnaire including five questions on diagnostic routines to the 40 paediatric clinics in university or regional hospitals in Sweden that perform small bowel biopsies. RESULTS: All 36 (90%) clinics that responded used anti-tissue transglutaminase antibodies as the initial diagnostic test and some also used serological markers. Most clinics (81%) used endoscopy and took multiple duodenal biopsies, whereas only a few (19%) occasionally employed a suction capsule. Almost all clinics (86%) omitted taking small bowel biopsies in symptomatic children with repeatedly high coeliac serology and positive genotyping, thereby avoiding the need for invasive endoscopy under anaesthesia. CONCLUSION: The 2012 Swedish Paediatric Coeliac Disease Diagnostic Guidelines had been widely accepted and implemented in routine health care two years after their introduction.

Maternal and perinatal conditions and the risk of developing celiac disease during childhood.

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.

High adherence to a gluten-free diet in adolescents with screening-detected celiac disease.

OBJECTIVES: The aim of the study was to evaluate the gluten-free diet (GFD) adherence after 1 year of follow-up in children with screening-detected celiac disease (CD) in a general population. METHODS: A total of 18,325 twelve-year-olds were invited to participate in a population-based CD screening (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 substudy included 210 children with TG2-IgA, evaluated both at the initial biopsy occasion and at 1-year follow-up. GFD adherence was evaluated by a combination of TG2-IgA measurements and self-reported adherence (n = 193). RESULTS: After 1 year, 85% (179/210) had normalized TG2-IgA levels (<5 U/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 of GFD adherence ("always" 82% [158/193] and "often" 16% [30/193]), and 75% [145/193] reported always adhering combined 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 highest TG2-IgA levels. CONCLUSIONS: GFD adherence is high in adolescents with CD detected by screening of the general population of Swedish 12-year-olds. Almost all of them had normalized serology and reported GFD adherence at the 1-year follow-up. A few adolescents who reported GFD adherence, however, had elevated TG2-IgA levels, suggesting more severe disease and/or nonadherence.

Celiac disease can be predicted by high levels of anti-tissue transglutaminase antibodies in population-based screening.

OBJECTIVES: The aim of the present study was 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 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines cover this group of patients. METHODS: The present study is a substudy of a cross-sectional CD screening study, Exploring the Iceberg of Celiacs in Sweden, a 2-phased study performed during 2005 to 2006 and 2009 to 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 those at the assessment of the biopsy. RESULTS: There were 267 children included, of whom 230 were diagnosed as having CD. Of all of the children, 67 children had low tTG-IgA levels (<5 U/mL), of whom 55% had Marsh 3 lesions. All of the children with tTG-IgA levels exceeding 10 times the upper limit of normal values of 5 U/mL, that is, 50 U/mL, were diagnosed as having CD. Lowering the cutoff to 3 U/mL, all but 1 child with 30 U/mL got CD diagnosis. CONCLUSIONS: By adopting the revised ESPGHAN criteria, biopsies could have been omitted in one-fourth of all of the patients. Our results indicate that the criteria may be useful even in screened children. Further studies are needed to confirm whether the 2012 ESPGHAN guidelines should be revised to also apply to the populations being screened.

Celiac disease risk varies between birth cohorts, generating hypotheses about causality: evidence from 36 years of population-based follow-up.

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.

Neighborhood conditions and celiac disease risk among children in Sweden.

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.

Prevotella jejuni sp. nov., isolated from the small intestine of a child with coeliac disease.

Five obligately anaerobic, Gram-stain-negative, saccharolytic and proteolytic, non-spore-forming bacilli (strains CD3 : 27, CD3 : 28(T), CD3 : 33, CD3 : 32 and CD3 : 34) are described. All five strains were isolated from the small intestine of a female child with coeliac disease. Cells of the five strains were short rods or coccoid cells with longer filamentous forms seen sporadically. The organisms produced acetic acid and succinic acid as major metabolic end products. Phylogenetic analysis based on comparative 16S rRNA gene sequence analysis revealed close relationships between CD3 : 27, CD3 : 28(T) and CD3 : 33, between CD3 : 32 and Prevotella histicola CCUG 55407(T), and between CD3 : 34 and Prevotella melaninogenica CCUG 4944B(T). Strains CD3 : 27, CD3 : 28(T) and CD3 : 33 were clearly different from all recognized species within the genus Prevotella and related most closely to but distinct from P. melaninogenica. Based on 16S rRNA, RNA polymerase ß-subunit (rpoB) and 60 kDa chaperonin protein subunit (cpn60) gene sequencing, and phenotypic, chemical and biochemical properties, strains CD3 : 27, CD3 : 28(T) and CD3 : 33 are considered to represent a novel species within the genus Prevotella, for which the name Prevotella jejuni sp. nov. is proposed. Strain CD3 : 28(T) ( = CCUG 60371(T) = DSM 26989(T)) is the type strain of the proposed novel species. All five strains were able to form homologous aggregates, in which tube-like structures were connecting individual bacteria cells. The five strains were able to bind to human intestinal carcinoma cell lines at 37 °C.

Transglutaminase IgA antibodies in a celiac disease mass screening and the role of HLA-DQ genotyping and endomysial antibodies in sequential testing.

OBJECTIVES: The aim of this study was to evaluate hypothetical screening strategies in a Swedish celiac disease (CD) mass screening. METHODS: Of 10,041 Swedish sixth graders born in 1993 invited to a population-based CD mass screening, 7208 participated. Anti-tissue transglutaminase (tTG) immunoglobulin (Ig) A were analyzed in all children and total serum IgA (s-IgA) in 7161 children. Additional analyses of tTG-IgG, endomysial antibodies (EMA) IgA and IgG, and human leukocyte antigen (HLA) alleles were performed according to a standardized protocol. Children with elevated levels of serological markers were recommended to undergo a small intestinal biopsy to verify diagnosis, and 153 children with CD were thus identified. Sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs) were calculated and receiver operating characteristic curves were plotted. RESULTS: By lowering the cutoff for tTG-IgA, 17 additional cases of CD were identified at the cost of 32 biopsies. All children with tTG-IgA >50 U/mL (10 times the recommended upper limit of normal) had gluten enteropathy. Area under the receiver operating characteristic curve for tTG-IgA was 0.988. All cases carried HLA-DQ2 or HLA-DQ8, as did 53% of the controls. For different hypothetical screening strategies, sensitivity, specificity, PPV, and NPV ranged between 87.6% and 100%, 99.5% and 99.9%, 79.7% and 89.7%, and 99.7% and 100%, respectively. Efforts to increase sensitivity by lowering tTG-IgA cutoff would result in increased number of small intestinal biopsies and lower PPV. Sequential testing for both EMA and HLA-DQ genotyping would reduce the number of negative small intestinal biopsies. CONCLUSIONS: tTG-IgA is a robust marker when used in CD mass screening and its performance can be enhanced by sequential testing for EMA or HLA-DQ genotyping.

Iron-deficiency anaemia, gastric hyperplasia, and elevated gastrin levels due to potassium channel dysfunction in the Jervell and Lange-Nielsen Syndrome.

AIM: We investigated extra-cardiac clinical symptoms and signs in the rare Jervell and Lange-Nielsen Syndrome, characterised by impaired KCNQ1 function, a gene essential for gastric acid secretion. METHODS: All Swedish Jervell and Lange-Nielsen cases with double KCNQ1 mutations (14 cases) were investigated by medical record review, an interview, and were offered laboratory testing for iron-deficiency anaemia and gastrointestinal markers. RESULTS: A history of iron-deficiency anaemia in 12 of 14 patients and subjective gastrointestinal symptoms in 13 of 14 patients was revealed. Previous endoscopy in five cases had revealed no case of coeliac or inflammatory bowel disease but three cases of mucosal hyperplasia/dysplasia. Current signs of anaemia or iron substitution were present in 9 of 12 tested cases. Elevated levels of gastrin in seven of nine cases, pepsinogen in six of seven cases, and faecal calprotectin in nine of nine cases were present. A significant correlation between elevated gastrin levels and concurrent iron-deficiency and/or anaemia was revealed (p-value 0.039). CONCLUSIONS: A high frequency of extra-cardiac clinical symptoms and previous medical investigations was found. We propose that the Jervell and Lange-Nielsen Syndrome phenotypically includes gastrointestinal symptoms/signs and secondary iron-deficiency anaemia owing to hypochlorhydria on the basis of KCNQ1 mutations. The resultant elevated gastrin level is a potential risk factor for later gastrointestinal cancer. Clinical monitoring with regard to developing anaemia and hypergastrinaemia should be considered in the Jervell and Lange-Nielsen Syndrome.

A gluten-free diet effectively reduces symptoms and health care consumption in a Swedish celiac disease population.

BACKGROUND: A gluten-free diet is the only available treatment for celiac disease. Our aim was to investigate the effect of a gluten-free diet on celiac disease related symptoms, health care consumption, and the risk of developing associated immune-mediated diseases. METHODS: A questionnaire was sent to 1,560 randomly selected members of the Swedish Society for Coeliacs, divided into equal-sized age- and sex strata; 1,031 (66%) responded. Self-reported symptoms, health care consumption (measured by health care visits and hospitalization days), and missed working days were reported both for the year prior to diagnosis (normal diet) and the year prior to receiving the questionnaire while undergoing treatment with a gluten-free diet. Associated immune-mediated diseases (diabetes mellitus type 1, rheumatic disease, thyroid disease, vitiligo, alopecia areata and inflammatory bowel disease) were self-reported including the year of diagnosis. RESULTS: All investigated symptoms except joint pain improved after diagnosis and initiated gluten-free diet. Both health care consumption and missed working days decreased. Associated immune-mediated diseases were diagnosed equally often before and after celiac disease diagnosis. CONCLUSIONS: Initiated treatment with a gluten-free diet improves the situation for celiac disease patients in terms of reduced symptoms and health care consumption. An earlier celiac disease diagnosis is therefore of great importance.

Identification of Childhood-Onset Inflammatory Bowel Disease in Swedish Healthcare Registers: A Validation Study.

Purpose: The Swedish National Patient Register (NPR) is often used in observational studies of childhood-onset inflammatory bowel disease (IBD) (<18 years of age) and its subtypes, but the validity of previously used register-based algorithms for capturing childhood-onset IBD has never been examined. Methods: We identified a random sample of 233 individuals with at least two first ever diagnostic listings of IBD in the NPR between 2002 and 2014. We calculated the test characteristics for different register-based definitions of IBD and its subtypes using the Copenhagen criteria and the revised Porto criteria as gold standard, both based on medical chart review. We made assumptions of the occurrence of undiagnosed IBD in the general child population based on available literature. Results: Out of 233 individuals with at least two diagnostic listings of IBD, 216 had true IBD, resulting in a positive predictive value (PPV) = 93% (95% confidence interval (CI) 89-96), sensitivity = 88% (95% CI 83-92), specificity = 100% (95% CI 100-100), and negative predictive value (NPV) = 100% (95% CI 100-100). The PPV for the NPR-based definitions of IBD subtypes at time of first IBD diagnosis and at end of follow-up were 78% (95% CI 69-86) and 88% (95% CI 80-94), respectively, for Crohn's disease and 74% (95% CI 63-83) and 71% (95% CI 60-80), respectively, for ulcerative colitis. Conclusion: The validity of register-based definitions of childhood-onset IBD in the Swedish NPR is high and can be used to identify patients in observational research.

Five-year follow-up of new cases after a coeliac disease mass screening.

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.

Delay to celiac disease diagnosis and its implications for health-related quality of life.

BACKGROUND: To determine how the delay in diagnosing celiac disease (CD) has developed during recent decades and how this affects the burden of disease in terms of health-related quality of life (HRQoL), and also to consider differences with respect to sex and age. METHODS: In collaboration with the Swedish Society for Coeliacs, a questionnaire was sent to 1,560 randomly selected members, divided in equal-sized age- and sex strata, and 1,031 (66%) responded. HRQoL was measured with the EQ-5D descriptive system and was then translated to quality-adjusted life year (QALY) scores. A general population survey was used as comparison. RESULTS: The mean delay to diagnosis from the first symptoms was 9.7 years, and from the first doctor visit it was 5.8 years. The delay has been reduced over time for some age groups, but is still quite long. The mean QALY score during the year prior to initiated treatment was 0.66; it improved after diagnosis and treatment to 0.86, and was then better than that of a general population (0.79). CONCLUSIONS: The delay from first symptoms to CD diagnosis is unacceptably long for many persons. Untreated CD results in poor HRQoL, which improves to the level of the general population if diagnosed and treated. By shortening the diagnostic delay it is possible to reduce this unnecessary burden of disease. Increased awareness of CD as a common health problem is needed, and active case finding should be intensified. Mass screening for CD might be an option in the future.

Accuracy in celiac disease diagnostics by controlling the small-bowel biopsy process.

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.

Proximal small intestinal microbiota and identification of rod-shaped bacteria associated with childhood celiac disease.

OBJECTIVES: Alterations in the composition of the microbiota in the intestine may promote development of celiac disease (CD). Using scanning electron microscopy (SEM) we previously demonstrated that rod-shaped bacteria were present on the epithelium of proximal small intestine in children with CD but not in controls. In this study we characterize the microbiota of proximal small intestine in children with CD and controls and identify CD-associated rod-shaped bacteria. METHODS: Proximal small intestine biopsies from 45 children with CD and 18 clinical controls were studied. Bacteria were identified by 16S rDNA sequencing in DNA extracted from biopsies washed with buffer containing dithiothreitol to enrich bacteria adhering to the epithelial lining, by culture-based methods and by SEM and transmission electron microscopy. RESULTS: The normal, mucosa-associated microbiota of proximal small intestine was limited. It was dominated by the genera Streptococcus and Neisseria, and also contained Veillonella, Gemella, Actinomyces, Rothia, and Haemophilus. The proximal small intestine microbiota in biopsies from CD patients collected during 2004-2007 differed only marginally from that of controls, and only one biopsy (4%) had rod-shaped bacteria by SEM (SEM+). In nine frozen SEM+ CD biopsies from the previous study, microbiotas were significantly enriched in Clostridium, Prevotella, and Actinomyces compared with SEM- biopsies. Bacteria of all three genera were isolated from children born during the Swedish CD epidemic. New Clostridium and Prevotella species and Actinomyces graevenitzii were tentatively identified. CONCLUSIONS: Rod-shaped bacteria, probably of the indicated species, constituted a significant fraction of the proximal small intestine microbiota in children born during the Swedish CD epidemic and may have been an important risk factor for CD contributing to the fourfold increase in disease incidence in children below 2 years of age during that time.

Celiac disease revealed in 3% of Swedish 12-year-olds born during an epidemic.

OBJECTIVE: 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.