Lars Stenhammar

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.

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.

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.

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.

Gut Microflora Associated Characteristics in Children with Celiac Disease

OBJECTIVES:The aim of the study was to investigate the metabolic function of intestinal microflora in children with celiac disease (CD) in order to find out if there is a deviant gut flora in CD patients compared to healthy controls.METHODS:The study group comprised children with CD, consecutively diagnosed according to current criteria given by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition. Thirty-six children were studied at presentation, i.e., on a normal gluten-containing diet, with clinical symptoms and signs indicative of CD, positive celiac serology markers, and a small bowel biopsy showing severe enteropathy. Forty-seven patients were studied when they had been on a gluten-free diet (GFD) for at least 3 months. For comparison, a group of 42 healthy controls (HC) were studied. The functional status of the intestinal microflora was evaluated by gas–liquid chromatography of short chain fatty acids (SCFAs) in fecal samples.RESULTS:There was a significant difference between untreated CD children and HC as well as between treated CD children and HC regarding acetic, i-butyric, i-valeric acid, and total SCFAs. The propionic and n-valeric acids differed significantly between CD children on GFD and HC. Moreover, there was a strong correlation between i-butyric and i-valeric acids in all study groups.CONCLUSIONS:This is the first study of the SCFA pattern in fecal samples from children with CD. The results indicate that there is a difference in the metabolic activity of intestinal microbial flora in children with CD compared to that in HC. The finding of a different pattern of some SCFAs in celiacs both at presentation and during treatment with GFD indicates that it is a genuine phenomenon of CD not affected by either the diet, the inflammation, or the autoimmune status of the patient.

Familial Prevalence of Coeliac Disease: a Twenty-Year Follow-up Study

Background: The genetic predisposition of coeliac disease (CD) is well known. Previous studies of first-degree relatives of coeliac patients have shown that as many as 10% have the disease. In 1981, we published a study in which all first-degree relatives of 32 index patients with CD were investigated by small-bowel biopsy. We found 2 relatives (2%) with CD. The present study is a re-investigation of all first-degree relatives of the same index patients performed 20-25 years after the first study to reveal any new cases of CD in this high-risk population. Methods: All 120 first-degree relatives were screened for CD by means of serological markers of CD. The relatives with positive markers were submitted to small-bowel biopsy. Results: Eight new cases of CD were found among the relatives. Two had been investigated by small-bowel biopsy 20 years previously, when they had only minor mucosal changes not classified as CD. The other six new cases of CD were found among offspring of the index patients and were born after completion of the previous study. Thus no new case of CD was found among those relatives who had a completely normal small-bowel biopsy 20-25 years previously. Conclusions: The high prevalence of CD among first-degree relatives of coeliac patients (8.3% in this study) supports the need to screen for CD in this high-risk population. Even relatives with only mild enteropathy should be followed carefully, since some may subsequently develop 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.

Better dietary compliance in patients with coeliac disease diagnosed in early childhood

Background: In coeliac disease (CD) there is a permanent gluten intolerance requiring life-long adherence to a strict gluten-free diet (GFD). An inadequate diet increases the risk for long-term complications. Coeliac patients often have great difficulty in maintaining a strictly GFD. We aimed to study whether young adults with CD diagnosed before the age of 4 years have a better dietary compliance than patients diagnosed later in life. Method: Twenty-nine adults with CD diagnosed in childhood were studied. They had had CD for 17-24 (mean 20) years. Their compliance to GFD was assessed using a questionnaire and serological markers (IgA and IgG anti-endomysium antibodies and IgA anti-tissue transglutaminase antibodies). Results: At least 80% of the coeliac patients who had been diagnosed before the age of 4 years complied with the GFD compared to 36% of the CD patients older than 4 years at diagnosis ( P r < r 0.05). Conclusion: This is the first study to show that patients with CD diagnosed before 4 years of age keep to a GFD significantly better than patients diagnosed after 4 years. It is thus important to diagnose childhood CD as early as possible in order to minimize the risk for reduced well-being and other potentially serious complications in coeliac individuals on an inadequate diet.BACKGROUND In coeliac disease (CD) there is a permanent gluten intolerance requiring life-long adherence to a strict gluten-free diet (GFD). An inadequate diet increases the risk for long-term complications. Coeliac patients often have great difficulty in maintaining a strictly GFD. We aimed to study whether young adults with CD diagnosed before the age of 4 years have a better dietary compliance than patients diagnosed later in life. METHOD Twenty-nine adults with CD diagnosed in childhood were studied. They had had CD for 17-24 (mean 20) years. Their compliance to GFD was assessed using a questionnaire and serological markers (IgA and IgG anti-endomysium antibodies and IgA anti-tissue transglutaminase antibodies). RESULTS At least 80% of the coeliac patients who had been diagnosed before the age of 4 years complied with the GFD compared to 36% of the CD patients older than 4 years at diagnosis (P < 0.05). CONCLUSION This is the first study to show that patients with CD diagnosed before 4 years of age keep to a GFD significantly better than patients diagnosed after 4 years. It is thus important to diagnose childhood CD as early as possible in order to minimize the risk for reduced well-being and other potentially serious complications in coeliac individuals on an inadequate diet.

Symptoms and signs have changed in Swedish children with coeliac disease.

Objective To examine symptoms and signs in children with coeliac disease and determine whether the clinical picture at disease onset has changed as incidence of the disease has decreased in the last 10 years. This project was part of the ABIS study (All Babies in Southeast Sweden, born from October 1997 to October 1999). Methods Eight paediatric departments in Southeast Sweden recorded all children with coeliac disease and registered symptoms according to a standard form. Data were obtained from 79 children with biopsy-confirmed coeliac disease, 43 contemporary controls, and 65 historic controls. Results When compared with children with normal intestinal biopsies, children with coeliac disease more often had abdominal distension (odds ratio [OR] = 22.17; 95% confidence interval [CI] OR = 5.00–98.25), thin extremities (OR = 5.89; 95% CI OR = 2.09–16.55), irritability (OR = 6.50; 95% CI OR = 1.83–23.03), and tiredness (OR = 15.43; 95% CI OR = 2.00–119.16). When compared with coeliac children diagnosed at ≤2 years of age in Gothenburg between 1985 and 1989, when the incidence of coeliac disease was three times higher, ABIS patients aged ≤2 years at diagnosis had less often experienced diarrhoea (OR = 0.23; 95% CI OR = 0.12–0.65), suboptimal weight gain (OR = 0.02; 95% CI OR = 0.01–0.10), or suboptimal linear growth (OR = 0.14; 95% CI OR = 0.05–0.39). Conclusion This study indicates that, in parallel to changes in incidence, clinical features of coeliac disease in young children have changed during the last 10 years.

Anti-endomysium and anti-gliadin antibodies as serological markers for coeliac disease in childhood: a clinical study to develop a practical routine.

Anti‐gliadin and anti‐endomysium antibodies were analysed in 174 children with suspected or verified coeliac disease with the aim of developing a practical routine. The biopsy was performed without knowledge of the antibody levels. To screen for coeliac disease is children younger than 2 years, we suggest the use of IgA anti‐gliadin antibodies, giving a sensitivity of 100% and a specificity of 86%. In older children both tests should be used in parallel, i.e. a biopsy should be performed if at least one of the tests is positive, giving a sensitivity of 98% and a specificity of 81%. To avoid unnecessary biopsy before mucosal relapse can be demonstrated during gluten challenge in a child without clinical symptoms, we suggest that the tests are used as serial testing, i.e. a biopsy should be performed if both tests are positive.