OBJECTIVE To evaluate HbA(1c) followed from diagnosis, as a predictor of severe microvascular complications (i.e., proliferative diabetic retinopathy [PDR] and nephropathy [macroalbuminuria]). RESEARCH DESIGN AND METHODS In a population-based observational study, 447 patients diagnosed with type 1 diabetes before 35 years of age from 1983 to 1987 in southeast Sweden were followed from diagnosis until 2019. Long-term weighted mean HbA(1c) (wHbA(1c)) was calculated by integrating the area under all HbA(1c) values. Complications were analyzed in relation to wHbA(1c) categorized into five levels. RESULTS After 32 years, 9% had no retinopathy, 64% non-PDR, and 27% PDR, and 83% had no microalbuminuria, 9% microalbuminuria, and 8% macroalbuminuria. Patients with near-normal wHbA(1c) did not develop PDR or macroalbuminuria. The lowest wHbA(1c) values associated with development of PDR and nephropathy (macroalbuminuria) were 7.3% (56 mmol/mol) and 8.1% (65 mmol/mol), respectively. The prevalence of PDR and macroalbuminuria increased with increasing wHbA(1c), being 74% and 44% in the highest category, wHbA(1c) >9.5% (>80 mmol/mol). In comparison with the follow-up done after 20-24 years duration, the prevalence of PDR had increased from 14 to 27% and macroalbuminuria from 4 to 8%, and both appeared at lower wHbA(1c) values. CONCLUSIONS wHbA(1c) followed from diagnosis is a very strong biomarker for PDR and nephropathy, the prevalence of both still increasing 32 years after diagnosis. To avoid PDR and macroalbuminuria in patients with type 1 diabetes, an HbA(1c) <7.0% (53 mmol/mol) and as normal as possible should be recommended when achievable without severe hypoglycemia and with good quality of life.

AimFrom 1986 to 1996, there was a four-fold increase in coeliac disease among young Swedish children, known as the Swedish coeliac epidemic. Children with type 1 diabetes have an increased risk of developing coeliac disease. We studied whether the prevalence of coeliac disease differed in children with type 1 diabetes born during and after this epidemic.MethodsWe compared national birth cohorts of 240 844 children born in 1992-1993 during the coeliac disease epidemic and 179 530 children born in 1997-1998 after the epidemic. Children diagnosed with both type 1 diabetes and coeliac disease were identified by merging information from five national registers.ResultsThere was no statistically significant difference in the prevalence of coeliac disease among children with type 1 diabetes between the two cohorts: 176/1642 (10.7%, 95% confidence interval 9.2%-12.2%) in the cohort born during the coeliac disease epidemic versus 161/1380 (11.7%, 95% confidence interval 10.0%-13.5%) in the post-epidemic cohort.ConclusionThe prevalence of having both coeliac disease and type 1 diabetes was not significantly higher in children born during, than after, the Swedish coeliac epidemic. This may support a stronger genetic disposition in children who develop both conditions.

Objectives Children with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti-tTG) that were >= 10 times the upper limit of normal (10x ULN) predicted CD in T1D. Methods Data from the Swedish prospective Better Diabetes Diagnosis study was used, and 2035 children and adolescents with T1D diagnosed between 2005-2010 were included. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti-tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti-tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh-Oberhuber classification. Results All of the 60 children with anti-tTG >= 10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti-tTG levels. Among 2003 screened children, 6.9% had positive anti-tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2035). All but one of the children diagnosed with CD had HLA-DQ2 and/or DQ8. Conclusions As all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a noninvasive method.

Introduction: Sudden cardiac death (SCD) in the young is rare and should always lead to suspicion of a genetic cardiac disorder. We describe a family, in which the proband was a girl deceased by sudden cardiac death in the playground at thirteen years of age. The index-patient had short stature, cleft palate but no previous cardiac symptoms. We found an uncommon cause of cardiomyopathy, due to a congenital disorder of glycosylation (CDG), previously described to cause a variable range of usually mild symptoms, and not previously found to cause SCD as the first symptom of the condition. Methods: The index patient underwent postmortem genetic testing/molecular autopsy for genes known to cause SCD, without a detection of causative agent, why two siblings of similar phenotype as the deceased sister underwent clinical-exome genetic sequencing (next generation sequencing). All first-degree relatives underwent clinical examination including cardiac ultrasound, Holzer-ECG, exercise stress test and biochemistry panel. Results: A genetic variant in the gene for phosphoglucomutase 1 (PGM1) was identified in the index patient and her two brothers, all were found to be homozygous for the genetic variant (G230E) NM_002633.2:c.689 G amp;gt; A in PGM1. This variant has been linked to a congenital disorder of glycosylation (PGM1-CDG), explaining the clinical picture of short stature, cleft palate, liver engagement and cardiomyopathy. During follow-up one of the brothers died unexpectedly after physical exertion during daily life at the age of twelve years. The other brother fainted during similar circumstances at the age of thirteen years. Both parents and three other siblings were found to be heterozygous gene carriers without risk for the disease. Conclusion: Our findings suggest that there is a need of multidisciplinary discussion and genetic testing after unexpected cardiac death in the young. We have to be more flexible in our evaluation of diseases and to consider even uncommon diseases including rare recessive inherited disorders. Our findings also suggest that the autosomal recessive PGM1-CDG might be highly associated with life-threatening cardiomyopathy with arrhythmia or sudden cardiac death as the first symptom presenting from childhood and adolescence.

Ischiospinal dysostosis (ISD) is a polytopic dysostosis characterized by ischial hypoplasia, multiple segmental anomalies of the cervicothoracic spine, hypoplasia of the lumbrosacral spine and occasionally associated with nephroblastomatosis. ISD is similar to, but milder than the lethal/semilethal condition termed diaphanospondylodysostosis (DSD), which is associated with homozygous or compound heterozygous mutations of bone morphogenetic protein-binding endothelial regulator protein (BMPER) gene. Here we report for the first time biallelic BMPER mutations in two patients with ISD, neither of whom had renal abnormalities. Our data supports and further extends the phenotypic variability of BMPER-related skeletal disorders.

ObjectivesReliable biomarkers in the early stages of idiopathic arthritis (JIA) are scarce and the disease heterogeneity makes it clinically challenging to predict the risk of joint damage. Biomarkers with prognostic potential are warranted in order to individualize treatment and follow-up in JIA. The soluble urokinase plasminogen activator receptor (suPAR) has been reported as an easily measurable biomarker for prognosis and severity in several rheumatic diseases but it has never been studied in JIA.MethodsSera from 51 well-characterized patients with JIA and 50 age- and sex-matched control subjects were collected and stored for later analysis of suPAR. Patients were carefully followed clinically over 3 years and analysis of erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (anti-CCP) were analyzed as part of clinical routine. Signs of joint erosions were evaluated by radiography.ResultsOverall, the levels of suPAR did not differ significantly between JIA patients and controls but those with polyarticular involvement showed higher suPAR (p = 0.013). In addition, elevated suPAR were associated with joint erosions (p = 0.026). Two RF/anti-CCP negative individuals with erosions showed high levels of suPAR.ConclusionsWe present new data on the biomarker suPAR in JIA. Our results indicate that, apart from RF and anti-CCP, analysis of suPAR could be of additional value in assessing the risk of erosions. Analysis of suPAR early could potentially guide treatment decision-making in JIA, but our observations should be confirmed in prospective studies.

AimsBetween 1985 and 1996, Sweden experienced an "epidemic" of celiac disease with a fourfold increase in incidence in young children. Timing and amount of gluten introduced during infancy have been thought to explain this "epidemic". We aimed to study whether the cumulative incidence of type 1 diabetes differs between children born during the "epidemic" compared to children born after.MethodsThis is a national register study in Sweden comparing the cumulative incidence of type 1 diabetes in two birth cohorts of 240 844 children 0-17 years old born 1992-1993, during the "epidemic", and 179 530 children born 1997-1998, after the "epidemic". Children diagnosed with type 1 diabetes were identified using three national registers.ResultsThe cumulative incidence of type 1 diabetes by the age of 17 was statistically significantly higher in those born after the "epidemic" 0.77% than in those born during the "epidemic" 0.68% (p < 0.001).ConclusionThe incidence of type 1 diabetes is higher in those born after the epidemic compared to those born during the epidemic, which does not support the hypothesis that gluten introduction increases the incidence of T1D. Changes in gluten introduction did not halt the increased incidence of type 1 diabetes in Sweden.

In the medical literature, diseases and syndromes are sometimes named after the first person to publish a report on, or describe, a condition. This is, of course, a great honour, both for the physician and his or her country and only a handful of Swedish medical researchers have achieved this. Swedish paediatrician Rolf Kostmann (Fig. 1) joined this elite group following his report on what he called infantile hereditary agranulocytosis (agranulocytosis infantilis hereditaria), which was first published 1950 in Swedish (1), and his dissertation in 1956 (2), He was the first to describe severe chronic neutropenia as an inherited disease. This article is protected by copyright.

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Extremely low birth weight (ELBW) infants often develop an altered gut microbiota composition, which is related to clinical complications, such as necrotizing enterocolitis and sepsis. Probiotic supplementation may reduce these complications, and modulation of the gut microbiome is a potential mechanism underlying the probiotic effectiveness. In a randomized, double-blind, placebo-controlled trial, we assessed the effect of Lactobacillus reuteri supplementation, from birth to post-menstrual week (PMW)36, on infant gut microbiota. We performed 16S amplicon sequencing in 558 stool samples from 132 ELBW preterm infants at 1 week, 2 weeks, 3 weeks, 4 weeks, PMW36, and 2 years. Probiotic supplementation results in increased bacterial diversity and increased L. reuteri abundance during the 1st month. At 1 week, probiotic supplementation also results in a lower abundance of Enterobacteriaceae and Staphylococcaceae. No effects were found at 2 years. In conclusion, probiotics may exert benefits by modulating the gut microbiota composition during the 1st month in ELBW infants.

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.

OBJECTIVEHbA(1c) is strongly related to the development of diabetes complications, but it is still controversial which HbA(1c) level to strive for in the treatment of type 1 diabetes. The aim of the current study was to evaluate HbA(1c), followed from diagnosis, as a predictor of severe microvascular complications and to formulate HbA(1c) target levels for treatment.RESEARCH DESIGN AND METHODSA longitudinal observation study followed an unselected population of 451 patients diagnosed with type 1 diabetes during 1983-1987 before the age of 35 years in a region of Southeast Sweden. Retinopathy was evaluated by fundus photography and nephropathy data collected from medical records. HbA(1c) was measured starting from diagnosis and during the whole follow-up period of 20-24 years. Long-term weighted mean HbA(1c) was then calculated. Complications were analyzed in relation to HbA(1c) levels.RESULTSThe incidence of proliferative retinopathy and persistent macroalbuminuria increased sharply and occurred earlier with increasing long-term mean HbA(1c). None of the 451 patients developed proliferative retinopathy or persistent macroalbuminuria below long-term weighted mean HbA(1c) 7.6% (60 mmol/mol); 51% of the patients with long-term mean HbA(1c) above 9.5% (80 mmol/mol) developed proliferative retinopathy and 23% persistent macroalbuminuria.CONCLUSIONSLong-term weighted mean HbA(1c), measured from diagnosis, is closely associated with the development of severe complications in type 1 diabetes. Keeping HbA(1c) below 7.6% (60 mmol/mol) as a treatment target seems to prevent proliferative retinopathy and persistent macroalbuminuria for up to 20 years.

We thank Dr. Takahara (1) for the comment on our recent article exploring the impact of HbA_1c, followed from diabetes onset, on the development of severe microvascular complications (2). As suggested, we have validated our results with Cox hazards analysis with severe microvascular events, i.e., laser-treated proliferative retinopathy and macroalbuminuria as a dependent variable and HbA_1c (mmol/mol) as a time-dependent covariate.

For laser-treated proliferative retinopathy, we found a hazard ratio of 1.038 (95% CI 1.025–1.052, P < 0.001) and for macroalbuminuria, a hazard ratio of 1.075 (95% CI 1.050–1.100, P < 0.001).

Analyzing our data with Cox hazards analysis thus shows the strong influence of long-term HbA_1c on severe microvascular complications, in agreement with our previous conclusions.

In our article, we chose to analyze and present the results in a way that was perhaps easier for a clinician to interpret and apply in clinical routine. With life-table analysis we found that the incidence of both laser-treated proliferative retinopathy and macroalbuminuria increased sharply and occurred earlier with increasing long-term weighted mean HbA_1c. In the same manner, the prevalence of microvascular complications increased steeply with higher long-term weighted mean HbA_1c, categorized in different groups.

In conclusion, our study irrespective of statistical methods shows a strong association between development of late complications and long-term mean HbA_1c, and keeping the average HbA_1c below 7.6% (60 mmol/mol) seemed sufficient to prevent microvascular complications for at least up to 20 years.

OBJECTIVE To evaluate sex, age at diabetes onset, puberty, and HbA1c, with subjects followed from diabetes diagnosis and during different time periods, as risk factors for developing diabetic simplex and proliferative retinopathy.

RESEARCH DESIGN AND METHODS In a population-based observational study, HbA1c for 451 patients diagnosed with diabetes before 35 years of age during 1983–1987 in southeast Sweden was followed for up to 18–24 years from diagnosis. Long-term mean weighted HbA1c(wHbA1c) was calculated. Retinopathy was evaluated by fundus photography and analyzed in relation to wHbA1c levels.

RESULTS Lower wHbA1c, diabetes onset ≤5 years of age, and diabetes onset before puberty, but not sex, were associated with longer time to appearance of simplex retinopathy. Proliferative retinopathy was associated only with wHbA1c. The time to first appearance of any retinopathy decreased with increasing wHbA1c. Lower wHbA1c after ≤5 years’ diabetes duration was associated with later onset of simplex retinopathy but not proliferative retinopathy. With time, most patients developed simplex retinopathy, except for those of the category wHbA1c≤50 mmol/mol (6.7%), for which 20 of 36 patients were without any retinopathy at the end of the follow-up in contrast to none of 49 with wHbA1c >80 mmol/mol (9.5%).

CONCLUSIONS Onset at ≤5 years of age and lower wHbA1c the first 5 years after diagnosis are associated with longer duration before development of simplex retinopathy. There is a strong positive association between long-term mean HbA1c measured from diagnosis and up to 20 years and appearance of both simplex and proliferative retinopathy.

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.

Aim The aim of our study was to examine whether there is a difference in coeliac disease prevalence in regard to parents education level and occupation, and whether this differs between screened and clinically diagnosed children at the age of 12 years. Methods The study, Exploring the Iceberg of Celiacs in Sweden (ETICS), was a school-based screening study of 12-year-old children that was undertaken during the school years 2005/2006 and 2009/2010. Data on parental education and occupation were reported from parents of the children. Specifically, by parents of 10 710 children without coeliac disease, 88 children diagnosed with coeliac disease through clinical care, and 231 who were diagnosed during the study. Results There were no statistically significant associations between occupation and coeliac disease for either the clinically detected (prevalence ratio 1.16; confidence interval 0.76-1.76) or screening-detected coeliac disease cases (prevalence ratio 0.86; confidence interval 0.66-1.12) in comparison with children with no coeliac disease. Also, there were no statistically significant associations for parental education and coeliac disease diagnosis. Conclusion There was no apparent relationship between coeliac disease and socio-economic position. Using parents socio-economic status as a tool to help identify children more likely to have coeliac disease is not recommended.

Objectives: Celiac disease (CD) is associated with thyroid autoimmunity and other autoimmune diseases. Data are, however, lacking regarding the relationship between thyroid autoimmunity and thyroid function, especially in regard to CD. Our aim was to investigate the impact of thyroid autoimmunity on thyroid function in 12-year-old children with CD compared to their healthy peers. Methods: A case-referent study was conducted as part of a CD screening of 12-year-olds. Our study included 335 children with CD and 1695 randomly selected referents. Thyroid autoimmunity was assessed with antibodies against thyroid peroxidase (TPOAb). Thyroid function was assessed with thyroid-stimulating hormone and free thyroxine. Results: TPOAb positivity significantly increased the risk of developing hypothyroidism in all children. The odds ratios (with 95% confidence intervals) were 5.3 (2.7-11) in healthy 12-year-olds, 10 (3.2-32) in screening-detected CD cases, 19 (2.6-135) in previously diagnosed CD cases, and 12 (4.4-32) in all CD cases together. Among children with TPOAb positivity, hypothyroidism was significantly more common (odds ratio 3.1; 95% CI 1.03-9.6) in children with CD (10/19) than in children without CD (12/46). Conclusions: The risk of thyroid dysfunction due to thyroid autoimmunity is larger for those with CD than their healthy peers. Our study indicates that a gluten-free diet does not reduce the risk of thyroid dysfunction. Further studies are required for improved understanding of the role of the gluten-free diet for the risk of autoimmune diseases in children with CD.

This Swedish study of children screened for coeliac disease and followed up five years later showed that around a third with positive serology but normal biopsy had since developed coeliac disease. Conversely, very few children with negative serology became coeliac. 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.

Lactobacillus reuteri DSM 17938 supplementation reduces morbidities in very low birth weight infants (&lt;1500 g), while the effect on extremely low birth weight infants (ELBW, &lt;1000 g) is still questioned. In a randomised placebo-controlled trial (ClinicalTrials.gov ID NCT01603368), head growth, but not feeding tolerance or morbidities, improved in L. reuteri-supplemented preterm ELBW infants. Here, we investigate colonisation with the probiotic strain in preterm ELBW infants who received L. reuteri DSM 17938 or a placebo from birth to postmenstrual week (PMW) 36. Quantitative PCR was used on 582 faecal DNA samples collected from 132 ELBW infants at one, two, three, and four weeks, at PMW 36, and at two years of age. Human milk oligosaccharides were measured in 31 milk samples at two weeks postpartum. At least 86% of the ELBW infants in the L. reuteri group were colonised with the probiotic strain during the neonatal period, despite low gestational age, high antibiotic pressure, and independent of infant feeding mode. Higher concentrations of lacto-N-tetraose, sialyl-lacto-N-neotetraose c, and 6 -sialyllactose in mothers milk weakly correlated with lower L. reuteri abundance. Within the L. reuteri group, higher L. reuteri abundance weakly correlated with a shorter time to reach full enteral feeding. Female sex and L. reuteri colonisation improved head growth from birth to four weeks of age. In conclusion, L. reuteri DSM 17938 supplementation leads to successful colonisation in ELBW infants.

The rapid development of paediatrics during the latter half of the 20th century led to organ‐specific subspecialities being established. One of these was paediatric gastroenterology, which was pioneered by enthusiasts at university departments during the 1960s and 1970s 1, 2. In 1975, the first two European paediatric gastroenterology textbooks appeared in English – ‘Paediatric Gastroenterology’ – edited by Charlotte Anderson and Valerie Burke and – ‘Diseases of the Small Intestine in Childhood’ – by John Walker‐Smith 3. Charlotte Anderson (1915–2002) was professor of paediatrics and child health and director of the Institute of Child Health at the University of Birmingham in the United Kingdom. Dr John Walker‐Smith (Fig. 1) was a London‐based consultant paediatrician and senior lecturer at the Medical College of St. Bartholomew′s Hospital (Barts) and the Queen Elizabeth Hospital for Children and later professor of paediatric gastroenterology at the Royal Free School of Medicine and Royal Free Hospital. He is now an emeritus professor. If we consider Charlotte Anderson to be the mother of European Paediatric Gastroenterology, then John Walker‐Smith is certainly the father....

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Seventy years ago, the Swedish pediatrician Rolf Kostmann (1909-1982) was the first to report on a previous unknown lethal hereditary neutropenia in infants, Kostmanns disease. This essay presents the man behind the syndrome rather than focusing on the disease itself.

Aim: Crohns disease (CD) is a chronic mucosal inflammation that affects the intestinal barrier function, for example, by altering the intestinal permeability. This pilot clinical study investigated the impact of oral human immunoglobulin (OHIG) treatment on permeability characteristics in children with active luminal Crohns disease. Methods: The study was performed at the Department of Paediatrics, Norrkoping Hospital, Sweden. Intestinal permeability was studied in three boys aged 13, 15 and 18 years with active CD, before and after a six-week treatment programme with OHIG, using different-sized polyethylene glycols as the test molecules. Three age-and sex-matched children with active CD treated with exclusive enteral nutrition (EEN) were also studied. Results: OHIG and EEN resulted in virtually similar reductions in the signs and symptoms of mucosal inflammation. However, OHIG, unlike EEN, appeared to normalise mucosal transfer leading to a normalisation of the maximum permeation of the small PEG molecules, as well as less restrictions of the larger PEG molecules. Conclusion: Our study found that OHIG appeared to normalise the mucosal barrier. This suggests that it could offer a new additional and versatile treatment for paediatric CD patients, with a minimal risk of adverse effects.

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Background- Aims

The features of pediatric celiac disease have changed in recent decades. We hypothesized that the age at diagnosis continued to increase, whereas the severity of symptoms should decrease.

Methods

In the present study, filed data about 1030 pediatric patients diagnosed with celiac disease between 1973 and 2013 were analysed. Available information covered 99.8% of the small bowel biopsies, and included information on sex, age, and clinical symptoms.

Results

The age at diagnosis increased significantly, from a mean of 2.2 years during the first 10 years to 8.2 years the current years. The proportion of children with severe symptoms declined from 92.8% to 78%, as did the proportion of biopsies characterized by severe pathology. In recent years, the monosymptomatic form of celiac disease has been more common, and the number of patients detected at screening has increased. The frequency of patients with gastrointestinal symptoms, extra-intestinal symptoms, and failure to thrive and/or short stature at presentation decreased.

Conclusions

The mean age of newly diagnosed patients increased the last 15 years. Currently celiac disease shows a less severe picture in terms of symptoms and intestinal pathology. Younger children suffer primarily from gastrointestinal symptoms and growth failure, and adolescents from extra-intestinal manifestations.

Objective

The prevalence of coeliac disease in Sweden during the “epidemic period” (1984−1996) was one of the highest in the world. The aim of this study was to assess the coeliac disease incidence in our region over the 41-year period, and how diagnostic activity and diagnostic accuracy were affected by the introduction of antibody testing. We also looked into how patients with mild enteropathy were evaluated.

Methods

In the county of Östergötland in Sweden, 2790 paediatric patients were investigated for suspected coeliac disease between 1973 and 2013. Notes were scrutinised for data on sex, age, histopathological reports and final diagnosis. For comparative purposes this period was divided into three sub-periods (1973−1983, 1984−1996 and 1997−2013) named pre-epidemic, epidemic and post-epidemic.

Results

Coeliac disease diagnosis was received by 1,030 patients. The peak incidence rate, 301 cases/100,000 in 1994 for the age group 0−1.9 years is the highest figure ever reported. The other age groups, 2−4.9, 5−14.9, and 15−17.9 years, also had high incidence rates. After the 1984−1996 “epidemic period” the incidence decreased for the youngest group but continued to increase for the other groups. The cumulative incidence at 18 years-of-age for children born 1994 reached 14 cases/1000 births, the highest figure hitherto reported. Diagnostic activity differed significantly between the three sub-periods (p<0.001) increasing gradually from 1984 and reaching a peak value of 0.87 in 2012. Cases of mild enteropathy were more frequently regarded as non-coeliac disease cases, decreasing significantly in the “postepidemic” period (p<0.001).

Conclusions

The incidence rate and cumulative incidence of coeliac disease among children were possibly the highest ever reported. Changes in diagnostic activity and accuracy could not be attributed to the introduction of new antibody tests, possibly because of other changes e.g. variations in the symptoms at presentation and improved knowledge of the disease among parents and health professionals.

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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, a2-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.

Background: Extremely preterm (EPT) infants born before gestational week (gw) 28 and with extremely low birth weight (ELBW, <1,000g) are at risk of  gastrointestinal complications such as feeding intolerance and necrotising enterocolitis (NEC). This contributes to suboptimal nutrition and growth restriction, which has been associated with a worse long-time neurodevelopmental outcome. The probiotic bacterium Limosilactobacillus reuteri DSM 17938 has previously been shown to reduce feeding intolerance when given to preterm infants. The effect of this and other probiotics have, however, been insufficiently studied in EPT-ELBW infants. One explanation for the lack of effect in many probiotic prevention studies in ELBW infants may be an extensive treatment with antibiotics.   

Exclusive breast milk feeding can prevent NEC, but the protective effect is incomplete. The variable content of prebiotic human milk oligosaccharides (HMO) has been suggested to explain this.  

Aims: To evaluate if oral supplementation with L. reuteri in EPT-ELBW infants improves feeding tolerance, growth rates and neurological development; reduces the prevalence of NEC and sepsis, by having effects on intestinal colonisation, and finally whether mother’s milk HMO composition impacts on NEC, sepsis, and growth.    

Methods: In total 134 newborn EPT-ELBW infants were randomised to enteral L. reuteri DSM 17938 supplementation or placebo administered from the first three days until gw 35 – 36 in a double-blind trial. Data was collected during intervention and at a standardised follow-up after 2 years. The primary outcome was time to full enteral feeding analysed with an intention to treat analysis. Secondary outcomes were NEC, culture proven sepsis, growth, and neurological development until two years of age. The breast milk content of 15 dominant HMOs in samples from 2 weeks, 4 weeks and in gw 35 – 36 was analysed with high performance anion-ex-change chromatography. L. reuteri-colonisation was determined with quantitative PCR in stool samples at 1, 2, 3 and 4 weeks, at gw 35 – 36 and at 2 years of age.  

Results: Median time to full enteral feeding was 15 days in both study groups. Probiotics were associated with an improved cranial growth during the first 28 days (-1.2 SD vs -1.7 SD; p<0.01). L. reuteri colonisation rate was 86-98% during the supplementation. After two years, infants supple-mented with L. reuteri had a better Bayley-III language mean score (score 90 vs 83, p<0.05). Low HMO diversity in the mother´s breast milk was associated with NEC development in the infant.   

Conclusion: L. reuteri did not reduce feeding intolerance in EPT-ELBW infants despite a high colonisation rate. The effect of probiotic supplementation on head growth and language development has not previously been reported and may suggest benefits of regulating the gut microbiota on brain development. A difference in HMO composition in breast milk may be an important factor explaining why exclusively breast milk fed EPT-ELBW infants are partially protected against development of NEC. These studies provide knowledge  and guidance for future strategies for feeding and pro-biotic supplementation in EPT-ELBW born children.   

Difference in human milk oligosaccharides (HMO) composition in breast milk may be one explanation why some preterm infants develop necrotizing enterocolitis (NEC) despite being fed exclusively with breast milk. The aim of this study was to measure the concentration of 15 dominant HMOs in breast milk during the neonatal period and investigate how their levels correlated to NEC, sepsis, and growth in extremely low birth weight (ELBW; amp;lt;1000 g) infants who were exclusively fed with breast milk. Milk was collected from 91 mothers to 106 infants at 14 and 28 days and at postmenstrual week 36. The HMOs were analysed with high-performance anion-exchange chromatography with pulsed amperometric detection. The HMOs diversity and the levels of Lacto-N-difucohexaose I were lower in samples from mothers to NEC cases, as compared to non-NEC cases at all sampling time points. Lacto-N-difucohexaose I is only produced by secretor and Lewis positive mothers. There were also significant but inconsistent associations between 3-sialyllactose and 6-sialyllactose and culture-proven sepsis and significant, but weak correlations between several HMOs and growth rate. Our results suggest that the variation in HMO composition in breast milk may be an important factor explaining why exclusively breast milk fed ELBW infants develop NEC.

Aim

This study evaluated if oral supplementation with the probiotic bacterium Lactobacillus reuteri DSM 17938 improved enteral feeding tolerance and growth rates in extremely low birthweight (ELBW) infants.

Method

A randomised, double‐blind, placebo‐controlled trial comprising 134 ELBW (<1000 g) infants born before gestational week 28 + 0. Daily supplementation of L. reuteri (1.25 × 108 bacteria/day) or placebo started within 3 days and continued until gestational week 36 + 0. Primary outcome was feeding tolerance and secondary outcome growth rate calculated as z‐score development.

Results

Feeding tolerance was similar in the probiotic and placebo group. Time to full enteral feeds was 15 days in both groups. The z‐score of the head circumference decreased in both groups from birth to day 28 of life, but it decreased less in the L. reuteri group compared to the placebo group: −1.2 SD (95% CI: −1.4 to −1.0) versus −1.7 SD (95% CI: −2.0 to −1.5; p = 0.001). Other growth parameters were similar in the study groups.

Conclusion

Lactobacillus reuteri did not reduce time to reach full enteral feeds in ELBW infants. The L. reuteri supplemented infants, however, had a better growth rate of the head during the first month of life.