Fredrik Norström

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.

Prevalence of Childhood Celiac Disease and Changes in Infant Feeding

OBJECTIVES: Between 1984 and 1996, Sweden experienced an “epidemic” of clinical celiac disease in children <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 cohort’s ascertained infant feeding. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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

BackgroundTo 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.MethodsIn 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.ResultsThe 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).ConclusionsThe 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.

How does unemployment affect self-assessed health? A systematic review focusing on subgroup effects

BackgroundAlmost all studies on the effect on health from unemployment have concluded that unemployment is bad for your health. However, only a few review articles have dealt with this relation in recent years, and none of them have focused on the analysis of subgroups such as age, gender, and marital status. The objective of our article is to review how unemployment relates to self-assessed health with a focus on its effect on subgroups.MethodsA search was performed in Web of Science to find articles that measured the effect on health from unemployment. The selection of articles was limited to those written in English, consisting of original data, and published in 2003 or later. Our definition of health was restricted to self-assessed health. Mortality- and morbidity-related measurements were therefore not included in our analysis. For the 41 articles included, information about health measurements, employment status definitions, other factors included in the statistical analysis, study design (including study population), and statistical method were collected with the aim of analysing the results on both the population and factor level.ResultsMost of the studies in our review showed a negative effect on health from unemployment on a population basis. Results at the factor levels were most common for gender (25 articles), age (11 articles), geographic location (8 articles), and education level (5 articles). The analysis showed that there was a health effect for gender, age, education level, household income, and geographic location. However, this effect differed between studies and no clear pattern on who benefits or suffers more among these groups could be determined. The result instead seemed to depend on the study context. The only clear patterns of association found were for socioeconomic status (manual workers suffer more), reason for unemployment (being unemployed due to health reasons is worse), and social network (a strong network is beneficial).ConclusionsUnemployment affects groups of individuals differently. We believe that a greater effort should be spent on specific groups of individuals, such as men or women, instead of the population as a whole when analysing the effect of unemployment on health.

Health-related quality of life in adolescents with screening-detected celiac disease, before and one year after diagnosis and initiation of gluten-free diet, a prospective nested case-referent study

BackgroundCeliac disease (CD) is a chronic disorder in genetically predisposed individuals in which a small intestinal immune-mediated enteropathy is precipitated by dietary gluten. It can be difficult to diagnose because signs and symptoms may be absent, subtle, or not recognized as CD related and therefore not prompt testing within routine clinical practice. Thus, most people with CD are undiagnosed and a public health intervention, which involves screening the general population, is an option to find those with unrecognized CD. However, how these screening-detected individuals experience the diagnosis and treatment (gluten-free diet) is not fully understood. The aim of this study is to investigate the health-related quality of life (HRQoL) of adolescents with screening-detected CD before and one year after diagnosis and treatment.MethodsA prospective nested case-referent study was done involving Swedish adolescents who had participated in a CD screening study when they were in the sixth grade and about 12 years old. Screening-detected adolescents (n = 103) and referents without CD who participated in the same screening (n = 483) answered questionnaires at the time of the screening and approximately one year after the screening-detected adolescents had received their diagnosis that included the EQ-5D instrument used to measure health status and report HRQoL.ResultsThe HRQoL for the adolescents with screening-detected CD is similar to the referents, both before and one year after diagnosis and initiation of the gluten-free diet, except in the dimension of pain at follow-up. In the pain dimension at follow-up, fewer cases reported problems than referents (12.6% and 21.9% respectively, Adjusted OR 0.50, 95% CI 0.27-0.94). However, a sex stratified analysis revealed that the significant difference was for boys at follow-up, where fewer screening-detected boys reported problems (4.3%) compared to referent boys (18.8%) (Adjusted OR 0.17, 95% CI 0.04-0.73).ConclusionsThe findings of this study suggest that adolescents with unrecognized CD experience similar HRQoL as their peers without CD, both before and one year after diagnosis and initiation of gluten-free diet, except for boys in the dimension of pain at follow-up.

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

BackgroundA 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.MethodsA 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.ResultsAll 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.ConclusionsInitiated 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.

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.

Health-related quality-of-life in children with coeliac disease, measured prior to receiving their diagnosis through screening

Objective To compare the health-related quality-of-life (HRQoL) of children with screening-detected coeliac disease (CD), before they learned of their diagnosis, with that of children without CD and in those previously diagnosed with CD. Methods In a cross-sectional CD screening study (‘ETICS’: Exploring the Iceberg of Coeliacs in Sweden), of 10,041 Swedish 12-year-olds invited, 7567 (75%) consented to participate, and 7208 (72%) children without previously diagnosed CD had serological markers analysed. Before the screening results were known, 7218 children (72%) and 6524 of their parents (65%) answered questionnaires. Questionnaires included the Swedish child-friendly pilot version of the EQ-5D instrument and proxy version of the EQ-5D instrument, which are generic tools used to describe HRQoL. Results We found no significant difference in HRQoL between the groups of children with screening-detected CD, without CD, and those previously diagnosed with CD. Conclusion The HRQoL reported by 12-year-olds with screening-detected CD, before they learned of their diagnosis, was not worse than that of the children without CD or those previously diagnosed with CD. Thus, mass screening for CD should not be justified on the basis that children with unrecognized CD have a poor HRQoL. However, because these children rated their HRQoL before diagnosis and treatment, they may not have recognized or perceived symptoms as severe enough to seek medical attention which demonstrates how difficult clinical/active case finding can be. Mass screening may still, therefore, be considered if the aim is early detection and prevention of future complications.

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.