Henry Ascher

Epidemic of coeliac disease in Swedish children.

Coeliac disease has emerged as a public health problem. The aim of the present study was to analyse trends in the occurrence of symptomatic coeliac disease in Swedish children from 1973 to 1997, and to explore any temporal relationship to changes in infant dietary patterns. We established a population‐based prospective incidence register of coeliac disease in 1991, and, in addition, retrospective data from 1973 were collected. A total of 2151 cases fulfilled the diagnostic criteria. Furthermore, we collected national data on a yearly basis on duration of breastfeeding, intake of gluten‐containing cereals and recommendations on when and how to introduce gluten into the diet of infants. From 1985 to 1987 the annual incidence rate in children below 2 y of age increased fourfold to 200‐240 cases per 100 000 person years, followed from 1995 by a sharp decline to the previous level of 50‐60 cases per 100 000 person years. This epidemic pattern is quite unique for a chronic disease of immunological pathogenesis, suggesting that prevention could be possible. The ecological observations made in this study are compatible with the epidemic being the result, at least in part, of a change in and an interplay among three factors within the area of infant feeding, i.e. amount of gluten given, age at introduction of gluten, and whether breastfeeding was ongoing or not when gluten was introduced. Other factor(s) may also have contributed, and the search for these should be intensified.

Oats to children with newly diagnosed coeliac disease: a randomised double blind study

Background: Treatment of coeliac disease (CD) requires lifelong adherence to a strict gluten free diet (GFD) which hitherto has consisted of a diet free of wheat, rye, barley, and oats. Recent studies, mainly in adults, have shown that oats are non-toxic to CD patients. In children, only open studies comprising a small number of patients have been performed. Aim: To determine if children with CD tolerate oats in their GFD. Patients and methods: In this double blind multicentre study involving eight paediatric clinics, 116 children with newly diagnosed CD were randomised to one of two groups: one group was given a standard GFD (GFD-std) and one group was given a GFD with additional wheat free oat products (GFD-oats). The study period was one year. Small bowel biopsy was performed at the beginning and end of the study. Serum IgA antigliadin, antiendomysium, and antitissue transglutaminase antibodies were monitored at 0, 3, 6, and 12 months. Results: Ninety three patients completed the study. Median (range) daily oat intake in the GFD-oats group (n = 42) was 15 (5–40) g at the six month control and 15 (0–43) g at the end of the study. All patients were in clinical remission after the study period. The GFD-oats and GFD-std groups did not differ significantly at the end of the study regarding coeliac serology markers or small bowel mucosal architecture, including numbers of intraepithelial lymphocytes. Significantly more children in the youngest age group withdrew. Conclusions: This is the first randomised double blind study showing that the addition of moderate amounts of oats to a GFD does not prevent clinical or small bowel mucosal healing, or humoral immunological downregulation in coeliac children. This is in accordance with the findings of studies in adult coeliacs and indicates that oats, added to the otherwise GFD, can be accepted and tolerated by the majority of children with CD.

Increasing incidence of childhood coeliac disease in Sweden. Results of a national study

A survey of the incidence of coeliac disease was carried out by asking all 43 paediatric departments in Sweden to report the number of children born between 1978 and 1987 in whom coeliac disease had been diagnosed. Thirty‐four departments representing a population of 7.18 million reported 1944 cases of coeliac disease among 804935 children born between 1978 and 1987. The cumulative incidence of coeliac disease was 1.7 per 1000 live births in children born between 1978 and 1982 and doubled to 3.5 per 1000 live births in children born after 1982. The highest incidence was found in the southern and south‐eastern regions of the country. The observed increase may have been influenced by changes in infant feeding practices such as the postponed age of introduction of gluten from four to six months of age and an increase in gluten content of proprietary baby foods.

Genome-wide Linkage Analysis of Scandinavian Affected Sib-pairs Supports Presence of Susceptibility Loci for Celiac Disease on Chromosomes 5 and 11

Celiac disease (CD) is a common chronic inflammatory disorder of the small intestine with a multifactorial aetiology. HLA is a well-known risk factor, but other genetic factors also influence disease susceptibility. To identify the genes involved in this disorder, we performed a genome-wide scan on 106 well-defined Swedish and Norwegian families with at least two affected siblings. We investigated familial segregation of 398 microsatellite markers, and utilised non-parametric linkage analysis. The strongest linkage with disease was found to the HLA locus (6p) (P<0.000006). There were eight regions besides HLA with a point wise P value below 0.05. Among these eight regions were 11q and 5q, both of which have been suggested in several linkage studies of independent celiac disease families. We also performed a stratification analysis of families according to their HLA genotypes. This resulted in significant differences on chromosome 2q. These results indicate that 11q, 5q and possibly also 2q are true susceptibility regions in CD.

Urban - rural disparities in antenatal care utilization: a study of two cohorts of pregnant women in Vietnam

BackgroundThe use of antenatal care (ANC) varies between countries and in different settings within each country. Most previous studies of ANC in Vietnam have been cross-sectional, and conducted in rural areas before the year 2000. This study aims to compare the pattern and the adequacy of ANC used in rural and urban Vietnam following two cohorts of pregnant women.MethodsA comparative study with two cohorts comprising totally 2132 pregnant women were followed in two health and demographic surveillance sites, one rural and one urban in Hanoi province, Vietnam. The women were quarterly interviewed using a structured questionnaire until delivery. The primary information obtained was the number and the content of ANC visits.ResultsAlmost all women reported some use of ANC. The average number of visits was much lower in the rural setting (4.4) than in the urban (7.7). In the rural area, 77.2% of women had at least three visits and 69.1% attended ANC during the first trimester. The corresponding percentages for the urban women were 97.2% and 97.2%. Only 20.3% of the rural women compared to 81.1% of the urban women received all core ANC services. As a result, the adequate use of ANC was 5.2 times in the urban than in the rural setting (78.3% compared to 15.2%). Nearly all women received ultrasound examination during pregnancy with a mean value of 6.0 scans per woman in the urban area and 3.5 in the rural. Most rural women used ANC at commune health centres and private clinics while urban women mainly visited public hospitals. Expenditure related to ANC utilization for the urban women was 7.1 times that for the urban women.ConclusionThe women in the rural area attended ANC later, had fewer visits and received much fewer services than urban women. The large disparity in ANC adequacy between the two settings suggests special attention for the ANC programme in rural areas focusing on its content. Revision and enforcement of the national guidelines to improve the behaviour and practice of both users and providers are necessary.

The risk of celiac disease in 107 families with at least two affected siblings.

Objectives Screening for celiac disease (CD) in the apparently healthy members of 107 nuclear families with two affected siblings (sib pair) and estimating the risk of CD in siblings and parents. Methods One hundred seven families from Sweden and southern Norway with at least two affected children were investigated. Frozen sera from 187 of the 192 healthy parents and from 94 of 95 siblings without diagnosed CD were examined for total immunoglobulin A (IgA) and anti-endomysial antibodies (EMA). Individuals with positive antibody titers underwent small intestinal biopsy. Results Positive test for EMA was found in 6 of 94 (6.3%) siblings without previously diagnosed CD and in 8 of 189 (4.2%) parents. CD was confirmed by small intestinal biopsy in all siblings and seven parents. The estimated risk for CD in multiply affected families was 26.3% for siblings and 12.9% for parents. An unexpected male preponderance was found among the new CD cases (10 males, 3 females). Conclusion The risk of CD in the members of nuclear families with two affected children is approximately three times higher than that when only one child is affected. The high male preponderance of new cases is unexpected and could not be explained fully by more silent disease in males as compared with females. Considering the high level of knowledge about CD in these families, the number of undiagnosed cases is surprisingly high. The authors suggest that serologic screening should be offered to all first-degree relatives of patients with CD.

Factors associated with antenatal care adequacy in rural and urban contexts-results from two health and demographic surveillance sites in Vietnam

BackgroundAntenatal Care (ANC) is universally considered important for women and children. This study aims to identify factors, demographic, social and economic, possibly associated with three ANC indicators: number of visits, timing of visits and content of services. The aim is also to compare the patterns of association of such factors between one rural and one urban context in northern Vietnam.MethodsTotally 2,132 pregnant women were followed from identification of pregnancy until birth in two Health and Demographic Surveillance Sites (HDSS). Information was obtained through quarterly face to face interviews.ResultsLiving in the rural area was significantly associated with lower adequate use of ANC compared to living in the urban area, both regarding quantity (number and timing of visits) and content. Low education, living in poor households and exclusively using private sector ANC in both sites and self employment, becoming pregnant before 25 years of age and living in poor communities in the rural area turned out to increase the risk for overall inadequate ANC. High risk pregnancy could not be demonstrated to be associated with ANC adequacy in either site. The medical content of services offered was often inadequate, in relation to the national recommendations, especially in the private sector.ConclusionLow education, low economic status, exclusive use of private ANC and living in rural areas were main factors associated with risk for overall inadequate ANC use as related to the national recommendations. Therefore, interventions focussing on poor and less educated women, especially in rural areas should be prioritized. They should focus the importance of early attendance of ANC and sufficient use of core services. Financial support for poor and near poor women should be considered. Providers of ANC should be educated and otherwise influenced to provide sufficient core services. Adherence to ANC content guidelines must be improved through enhanced supervision, particularly in the private sector.

In the Best Interest of the Child? The Politics of Vulnerability and Negotiations for Asylum in Sweden

This article concerns the interplay between government policy and practice and refugee childrens welfare as these issues have been brought to the fore in public debate and controversy in the recent past in Sweden. Framed by the tension between immigration law and human rights conventions such as the UN Convention on the Rights of the Child (CRC), incidences of ill-health and suffering among asylum-seeking children have both spurred public concerns over their vulnerability and welfare and questioned the authenticity and legitimacy of their claims. The images reflect the ambiguous constructions of refugee children and their families either as victims or as untrustworthy ‘others’. The article addresses the ways in which the focus on children resonates particularly in the Swedish context, related both to a long-standing concern with childrens wellbeing and to a Swedish self-image as international model for childrens rights. The issues manifested in the Swedish context form part of a wider problematic: suffering and vulnerability are expressions of, but also a potential resource in, an extremely harsh situation of severely limited options; they also have something to say about the risks of ‘humanitarianism’ and the changing terms of asylum in Europe today.

How do Swedish paediatric clinics diagnose coeliac disease? Results of a nationwide questionnaire study

Background and aim: Diagnosis of coeliac disease is based on the demonstration of enteropathy in a small bowel biopsy. Correct diagnosis is of utmost importance, since the need for dietary management is life long, and inadequate treatment may lead to potentially serious complications. The Swedish Working Group for Paediatric Coeliac Disease has published guidelines for the diagnosis of childhood coeliac disease. The present questionnaire was designed in order to create the basis for revision of those guidelines. Methods: In 2004, a nationwide questionnaire concerning current diagnostic routines was sent to all 45 paediatric clinics performing small bowel biopsy. All clinics responded. Results: All clinics base their diagnosis on small bowel biopsy findings at presentation. Furthermore, in 24 (53%) of the clinics, children with suspected coeliac disease are investigated by small bowel biopsy both at presentation and follow‐up while on a gluten‐free diet. Eighteen (40%) of the clinics employ a different diagnostic routine for children under 2 y of age than for those older than 2 y. All clinics use coeliac serological testing at various stages of the diagnostic procedure.

A Possible Mechanism behind Autoimmune Disorders Discovered By Genome-Wide Linkage and Association Analysis in Celiac Disease

Celiac disease is a common autoimmune disorder characterized by an intestinal inflammation triggered by gluten, a storage protein found in wheat, rye and barley. Similar to other autoimmune diseases such as type 1 diabetes, psoriasis and rheumatoid arthritis, celiac disease is the result of an immune response to self-antigens leading to tissue destruction and production of autoantibodies. Common diseases like celiac disease have a complex pattern of inheritance with inputs from both environmental as well as additive and non-additive genetic factors. In the past few years, Genome Wide Association Studies (GWAS) have been successful in finding genetic risk variants behind many common diseases and traits. To complement and add to the previous findings, we performed a GWAS including 206 trios from 97 nuclear Swedish and Norwegian families affected with celiac disease. By stratifying for HLA-DQ, we identified a new genome-wide significant risk locus covering the DUSP10 gene. To further investigate the associations from the GWAS we performed pathway analyses and two-locus interaction analyses. These analyses showed an over-representation of genes involved in type 2 diabetes and identified a set of candidate mechanisms and genes of which some were selected for mRNA expression analysis using small intestinal biopsies from 98 patients. Several genes were expressed differently in the small intestinal mucosa from patients with celiac autoimmunity compared to intestinal mucosa from control patients. From top-scoring regions we identified susceptibility genes in several categories: 1) polarity and epithelial cell functionality; 2) intestinal smooth muscle; 3) growth and energy homeostasis, including proline and glutamine metabolism; and finally 4) innate and adaptive immune system. These genes and pathways, including specific functions of DUSP10, together reveal a new potential biological mechanism that could influence the genesis of celiac disease, and possibly also other chronic disorders with an inflammatory component.