Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study.

OBJECTIVES: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D). PATIENTS AND METHODS: Dried blood spots and serum samples were taken at diagnosis from children <18 years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA). RESULTS: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p = .00001) and those with DQX/X (p ≤ .00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p = .018). CONCLUSION: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD.

Efficacy and safety of granulocyte, monocyte/macrophage adsorptive in pediatric ulcerative colitis.

AIM: To investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis. METHODS: The ADAPT study was a prospective, open-label, multicenter study in pediatric patients with moderate, active ulcerative colitis with pediatric ulcerative colitis activity index (PUCAI) of 35-64. Patients received one weekly apheresis with Adacolumn(®) granulocyte, monocyte/macrophage adsorptive (GMA) apheresis over 5 consecutive weeks, optionally followed by up to 3 additional apheresis treatments over 3 consecutive weeks. The primary endpoint was the change in mean PUCAI between baseline and week 12; the secondary endpoint was improvement in PUCAI categorized as (Significant Improvement, PUCAI decrease of ≥ 35), Moderate Improvement (PUCAI decrease of 20 < 35), Small Improvement (PUCAI decrease of 10 < 20) or No change (PUCAI decrease of < 10). RESULTS: Twenty-five patients (mean age 13.5 years; mean weight 47.7 kg) were enrolled. In the intention-to-treat set (ITT), the mean value for PUCAI improvement was 22.3 [95%CI: 12.9-31.6; n = 21]. In the per-protocol (PP) set, the mean improvement was 36.3 [95%CI: 31.4-41.1; n = 8]. Significant Improvement was recorded for 9 out of 20 patients (45%); 5 out of 20 patients (25%) had Moderate Improvement and one patient (5%) had No Change in PUCAI score at week 12. In the PP set, six out of eight patients (75%) showed Significant Improvement; and in two out of eight patients (25%) Moderate Improvement was recorded. The endoscopic activity index (EAI) decreased by 3 points on average. Seven (7) out of 21 (33%) patients in ITT and 4 out of 8 (50%) patients in PP have used steroids during the clinical investigation. The mean steroid dosage for these patients in the ITT set decreased from a mean 12.4 mg to 10 mg daily on average from Baseline to week 12. CONCLUSION: Adacolumn(®) GMA apheresis treatment was effective in pediatric patients with moderate active Ulcerative Colitis. No new safety signals were reported. The present data contribute to considering GMA apheresis as a therapeutic option in pediatric patients having failed first line therapy.

Presentation and progression of childhood-onset inflammatory bowel disease in Northern Stockholm County.

BACKGROUND: Some studies have suggested that childhood-onset inflammatory bowel disease (IBD) is characterized by extensive intestinal involvement and rapid progression to complications. Here, we report the presentation and progression of patients diagnosed with IBD during childhood in a population-based cohort from northern Stockholm County. METHODS: Medical records for all 280 patients diagnosed in the period 1990-2007 with childhood-onset IBD in northern Stockholm County were followed until 2011 (median follow-up time, 8.8 yr). Disease phenotypes were classified according to the Paris pediatric IBD classification. RESULTS: Among the 74 patients with ulcerative colitis, 72% presented with pancolitis. Among the 200 patients with Crohn's disease (CD), 75% presented with colitis. Complicated disease behavior was observed in 18% of patients with CD by end of follow-up. Extension of the disease territory was observed in 22% of patients with ulcerative colitis and 15% of patients with CD. The cumulative risk of intra-abdominal surgery after 10 years was 8% (95% confidence interval, 4%-20%) for ulcerative colitis and 22% (95% confidence interval, 15%-28%) for patients with CD. Nonmucosal healing at 1 year was associated with a complicated disease course in patients with CD (hazard ratio = 14.56; 95% confidence interval, 1.79-118.68; P = 0.01). CONCLUSIONS: Patients with childhood-onset IBD were characterized by extensive colitis that was relatively stable over time and associated with a relatively low risk of complications and abdominal surgery. Our findings confirm the more extensive disease location in pediatric IBD but did not identify the proposed dynamic and aggressive nature of the childhood-onset phenotype. The association of nonmucosal healing with a complicated disease course suggests that endoscopy should guide treatment intensity in childhood-onset CD.

Jejunostomy enteral feeding in children: outcome and safety.

BACKGROUND: The aim of this study was to report on the clinical outcome and safety of jejunostomy tube feeding used in our clinical setting for more than 14 years. MATERIAL AND METHODS: A retrospective study of all children who underwent a surgical catheter jejunostomy placement between July 1996 and March 2010 was conducted. Data were collected regarding the outcome and complications. RESULTS: Thirty-three children (14 girls) were included. The median age at the time of primary surgery was 1.43 years (range, 0.15-17.7 years), and the median time of follow-up was 2.34 years (range, 0.27-12.6 years). Seventeen children were severely neurologically impaired (NI). Surgical insertion of a jejunostomy tube was performed due to 1 or more of the following indications: gastroesophageal reflux disease (GERD), failure to thrive, recurrent pneumonia, esophageal disease, or oral feeding difficulties. The effect of the indications showed a reduction in GERD and pneumonia. Feeding difficulties also decreased. Weaning was possible in 12 of 16 children without NI but in only 2 of 17 with NI. Major complications requiring surgical reoperation affected 8 children. No mortality was related to the jejunostomy feeding catheter. CONCLUSION: In selected cases, surgically placed jejunostomy tubes for feeding in children is an effective and safe method to overcome GERD, feeding difficulties, or recurrent pneumonia without major surgery.

High prevalence of celiac disease in Swedish children and adolescents with type 1 diabetes and the relation to the Swedish epidemic of celiac disease: a cohort study.

AIM: The aim was to determine the prevalence and clinical and temporal relationship of celiac disease (CD) in a population of Swedish children with type 1 diabetes mellitus (T1DM) before, during, and after the Swedish epidemic of CD (birth cohorts 1984-1996). METHODS: Retrospective chart review between 1995 and 2005 was conducted of 1151 children (0-18 years old, born 1981-2004) with T1DM. RESULTS: A prevalence of 9.1% (95% CI: 7.2-11.2) of CD in T1DM children was found. No significant difference in prevalence of CD was observed in different birth years, in contrast to the Swedish epidemic of CD. Sixty-two percent of children diagnosed with CD after T1DM onset had pathological levels of antibodies within the first 24 months. The presence or absence of gastrointestinal symptoms had no predictable value for biopsy-confirmed CD or not. CONCLUSION: The onset of CD in the T1DM population does not follow the pattern of the general population during the Swedish epidemic of CD. The shared genetic component in the human leukocyte antigen region in cases with comorbidity of CD and T1DM may overrule other CD-causing factors in the general population. Children with T1DM should be screened for CD at diagnosis and repeatedly at least during the first 2 years, even if asymptomatic.

Increasing incidence of paediatric inflammatory bowel disease in northern Stockholm County, 2002-2007.

OBJECTIVES: A sharp increase in paediatric (younger than 16 years) inflammatory bowel disease (IBD) incidence was observed in northern Stockholm County, Sweden, in 1990-2001. The increasing incidence was primarily explained by a rising incidence of Crohn disease (CD). Here, we present an update on the trends in incidence of paediatric IBD, 2002-2007. METHOD: Medical records of all children diagnosed as having suspected IBD in northern Stockholm County, 2002-2007, were scrutinised using defined diagnostic criteria. Disease extension, localisation, and behaviour at diagnosis were classified within the framework of the Paris classification. RESULT: A total of 133 children were diagnosed as having IBD 2002-2007 corresponding to a sex- and age-standardised incidence (per 10 person-years) for paediatric IBD of 12.8 (95% CI 10.8-15.2). The standardised incidence was 9.2 (95% CI 7.5-11.2) for CD and 2.8 (95% CI 1.9-4.0) for ulcerative colitis (UC). A significant increasing incidence of UC (P < 0.05) was observed during the study period. No temporal trend was observed for the incidence of CD. CONCLUSIONS: The incidence rate of paediatric IBD in northern Stockholm was significantly higher in 2002-2007 than that observed in our earlier study covering 1990-2001. The former sharp increase in incidence of paediatric CD seems, however, to have levelled out, although at a higher rate than reported from most other regions in the world. Although CD was still predominant, the observed increase in incidence of UC during the study period is notable.

Down syndrome is associated with elevated risk of celiac disease: a nationwide case-control study.

OBJECTIVE: To provide risk estimates for celiac disease (CD) in Down syndrome (DS) compared with the general population. STUDY DESIGN: In this nationwide Swedish case-control study, we examined the risk of CD in individuals with DS born between 1973 and 2008. Study participants consisted of 2 populations: 11,749 patients with biopsy-verified CD (villous atrophy [VA], equivalent to Marsh grade III) who were identified through histopathology reports from the 28 pathology departments in Sweden and 53,887 population-based controls matched for sex, age, calendar year of birth, and county of residence. We used prospectively recorded data from Swedish health registers to identify individuals with DS. ORs were calculated using conditional logistic regression. RESULTS: Of the 11,749 individuals with CD, 165 had a diagnosis of DS (1.4%) compared with 55/53,887 controls (0.1%). This corresponded to an OR of 6.15 (95% CI = 5.09-7.43) for subsequent CD in individuals with DS compared with the general population. The association between DS and CD was not affected by maternal age at delivery, infant sex, or presence of type 1 diabetes mellitus in the child. CONCLUSIONS: We found a sixfold increased risk of CD in individuals with DS. This study adds precision to the previously reported association between DS and CD.

Antibodies against deamidated gliadin peptides and tissue transglutaminase for diagnosis of pediatric celiac disease.

OBJECTIVES: The aim of the present study was to evaluate diagnostic performance and actual costs in clinical practice of immumoglobulin (Ig)G/IgA deamidated gliadin peptide antibodies (DGP) as a complement to IgA antibodies against tissue transglutaminase (tTG) for the diagnosis of pediatric celiac disease (CD). METHODS: All of the consecutive patients younger than 18 years tested for tTG and/or DGP, who underwent duodenal biopsy because of suspected CD in Stockholm and Gothenburg, Sweden, from 2008 to 2010, were included. Medical records were reviewed. RESULTS: Of 537 children who underwent duodenal biopsy, 278 (52%) had CD. A total of 71 (13%) were younger than 2 years and 16 (4%) had IgA deficiency. Sensitivity and specificity for tTG were 94% and 86%, respectively. Corresponding values for DGP were 91% and 26%. Positive predictive values (PPV) were 88% for tTG and 51% for DGP. There were 148 children who were tTG-negative and DGP-positive, of which only 5% (8/148) had villous atrophy. Among children younger than 2 years with normal IgA, PPV was 96% (25/26) for tTG and 48% (24/50) for DGP. In 16 IgA-deficient children, 11 were DGP positive, of which 5 had CD (PPV 45%). Eight of 278 cases of CD would possibly have been missed without DGP. The cost of adding DGP and consequently more biopsies to be able to detect 8 extra cases of CD was [Euro sign]399,520 or [Euro sign]49,940 per case. CONCLUSIONS: For diagnosing CD, tTG is superior to DGP, even in children younger than 2 years. Combining tTG and DGP does not provide a better tradeoff between number of missed cases of CD, number of unnecessary duodenal biopsies, and cost than tTG alone.

Cesarean section and the risk of pediatric Crohn's disease.

BACKGROUND: Crohn's disease (CD) could involve an inappropriate immune response against normal bowel flora. Disrupted or atypical patterns of microbial bowel colonization may impair development of homeostasis between gut flora and the immune system. Perinatal microbial exposures may be particularly important in stimulating intestinal immune recognition. As birth by cesarean section is thought to represent an atypical pattern of early bowel colonization, we examined its association with pediatric CD. METHODS: Some 1536 patients diagnosed with pediatric CD and 15,439 controls matched by delivery unit, week of birth, sex, and born between 1973 and 2006 were identified through Swedish registers. The association of birth by cesarean section with pediatric CD was examined using conditional logistic regression, with stratification by sex and adjustment for parental socioeconomic index and maternal infections during pregnancy. RESULTS: Birth by cesarean section is associated with a modestly increased risk for pediatric CD among boys (odds ratio [OR] = 1.25, 95% confidence interval [CI] 1.01-1.54) but not girls, (OR = 0.99, 95% CI 0.76-1.29) and elective cesarean section is associated with a modest increased risk for the entire population (OR = 1.36, 95% CI 1.02-1.80). CONCLUSIONS: This study does not suggest that the delivery procedure should be altered, but the findings may be of etiological significance in CD, indicating a potential role for perinatal exposures associated with delivery mode. Although the sex difference may have arisen by chance, the modestly increased CD risk for boys delivered by cesarean section is consistent with sex-specific differences in susceptibility to some exposures.

Acid reducing agents to neonates - lack of evidence and guidelines.

OBJECTIVE: The aim of this retrospective study was to investigate the clinical practice, i.e. the frequency of use and the treatment strategies, for acid reducing drugs to neonates in a Swedish hospital. METHODS: Retrospective reviews of charts and interviews with nurses at the neonatal wards of Karolinska University Hospital were performed to identify difficulties that might occur with drug administration. All patients admitted over a 2-month period were included. Main outcome measure were the number of patients treated with acid reducing drugs and the dosages. RESULTS: Nine out of 215 patients (4.2%) received an acid reducing drug. Patients treated with acid reducing drugs had significantly lower birth weight, lower gestational age and longer duration of hospitalization. Eight of the patients were treated with omeprazole. One of these patients started treatment with omeprazole but continued later on with ranitidine. One patient was exclusively treated with ranitidine. The doses of omeprazole (intravenous or oral administration) were within the range 0.16-1.26 mg/kg/day. CONCLUSIONS: A wide variation in treatment regimens of acid reducing drugs is given to newborn infants. The percentage of treated children was much lower than earlier reports from the US and UK. No conclusions can be drawn as to whether the doses and dosing intervals used give sufficient acid suppression, since the effect of the therapy was not recorded. The present study is only retrospective and data are not truly comparable with other studies. Further studies are therefore warranted to evaluate effective doses and pharmacokinetics of acid reducing drugs in newborn infants.

Prevalence of Helicobacter pylori in HIV-infected, HAART-naïve Ugandan children: a hospital-based survey.

BACKGROUND: The aim of this survey was to determine the prevalence of and factors associated with Helicobacter pylori (H. pylori) colonization in HIV-infected, highly active antiretroviral therapy-naïve Ugandan children aged 0-12 years. METHODS: In a hospital-based survey, 236 HIV-infected children were tested for H. pylori colonization using a faecal antigen test. A standardized interview with socio-demographic information and medical history was used to assess risk factors. A cluster of differentiation 4 (CD4) cell percentage was prevalent in most children. RESULTS: The overall prevalence of H. pylori in the HIV-infected children was 22.5%. Age-specific prevalence was as follows: up to one year, 14.7%; 1-3 years, 30.9%; and 3-12 years, 20.7%. HIV-infected children who were more seriously affected by their disease (low CD4 cell percentage or WHO clinical stage II-IV) were less likely to be colonized with H. pylori. There was a trend for a lower prevalence of H. pylori in children who had taken antibiotics for the preceding two weeks (21.6%) than in those who had not taken antibiotics (35.7%). There was no statistically significant difference in prevalence by gender, housing, congested living, education of the female caretaker, drinking water or toilet facilities. CONCLUSIONS: HIV-infected, HAART-naïve Ugandan children had a lower prevalence of H. pylori colonization compared with apparently healthy Ugandan children (44.3%). Children with a low CD4 cell percentage and an advanced clinical stage of HIV had an even lower risk of H. pylori colonization. Treatment with antibiotics due to co-morbidity with infectious diseases is a possible explanation for the relatively low prevalence.

Faecal calprotectin concentrations in apparently healthy children aged 0-12 years in urban Kampala, Uganda: a community-based survey.

BACKGROUND: Calprotectin is a calcium and zinc binding protein, abundant in neutrophils and is extremely stable in faeces. Faecal calprotectin is used as a non-specific marker for gastrointestinal inflammation. It has a good diagnostic precision to distinguish between irritable bowel syndrome and inflammatory bowel disease. Studies have established normal concentrations in healthy children; all these studies have been performed in high-income countries. The objective of this study was to determine the concentration of faecal calprotectin in apparently healthy children aged 0-12 years in urban Kampala, Uganda. METHOD: We tested 302 apparently healthy children aged, age 0-12 years (162 female, 140 male) in urban Kampala, Uganda. The children were recruited consecutively by door-to-door visits. Faecal calprotectin was analyzed using a quantitative enzyme-linked immunosorbent assay. Faeces were also tested for Helicobacter pylori (H. pylori) antigen, for growth of enteropathogens and microscopy was performed to assess protozoa and helminths. A short standardized interview with socio-demographic information and medical history was obtained to assess health status of the children. RESULTS: In the different age groups the median faecal calprotectin concentrations were 249 mg/kg in 0 < 1 year (n = 54), 75 mg/kg in 1 < 4 years (n = 89) and 28 mg/kg in 4 < 12 years (n = 159). There was no significant difference in faecal calprotectin concentrations and education of female caretaker, wealth index, gender, habits of using mosquito nets, being colonized with H. pylori or having other pathogens in the stool. CONCLUSION: Concentrations of faecal calprotectin among healthy children, living in urban Ugandan, a low-income country, are comparable to those in healthy children living in high-income countries. In children older than 4 years, the faecal calprotectin concentration is low. In healthy infants faecal calprotectin is high. The suggested cut-off concentrations in the literature can be used in apparently healthy Ugandan children. This finding also shows that healthy children living under poor circumstances do not have a constant inflammation in the gut. We see an opportunity to use this relatively inexpensive test for further understanding and investigations of gut inflammation in children living in low-income countries.

Helicobacter pylori in apparently healthy children aged 0-12 years in urban Kampala, Uganda: a community-based cross sectional survey.

BACKGROUND: Helicobacter pylori is one of the most common causes of bacterial infection in human beings. Studies have showed a high prevalence of Helicobacter pylori among people in low-income countries and colonization early in life. A monoclonal antigen test, performed on faeces, HpSA ImmunoCardSTAT, has a high sensitivity, specificity and accuracy and the faecal test can be performed in all ages, also in resource-limited settings. The main objective of this study was to determine the prevalence and factors associated with Helicobacter pylori colonization in apparently healthy children aged 0-12 years in urban Kampala, Uganda. METHOD: We tested 427 apparently healthy children, age 0-12 years (211 males, 216 females), in a cross sectional survey for Helicobacter pylori colonization using HpSA ImmunoCardSTAT. A short standardized interview with socio-demographic information and medical history was used to assess risk factors. RESULTS: The overall prevalence of Helicobacter pylori in the 427 children was 44.3% (189 out of 427). Early colonization was common, 28.7%, in children younger than 1 year of age. The age specific rates were 46.0% in children age 1- < 3 years, 51.7% in children age 3- < 6 years, 54.8% in children age 6- < 9 years and 40.0% in children age 9- < 12 years. There was a significant difference in prevalence by gender; female 38.5% versus male 49.8% and by type of housing; permanent house 38.5% versus semi-permanent house 48.6%. Congestive living and education level of the female caretaker showed a clear trend for a difference in prevalence. Factors independently associated with Helicobacter pylori colonization included: drugs taken last three months, using a pit latrine, sources of drinking water and wealth index. CONCLUSION: The prevalence of Helicobacter pylori colonization among urban Ugandan children is high at an early age and increases with age. The impact of Helicobacter pylori colonization on children's health in Uganda needs to be further clarified.

Evaluation of 99mTc-HMPAO leukocyte scintigraphy in the investigation of pediatric inflammatory bowel disease.

OBJECTIVE: To evaluate (99m)Tc-HMPAO leukocyte scintigraphy as an investigation for inflammatory bowel disease (IBD). STUDY DESIGN: Scintigraphy was performed in 95 children undergoing investigation for IBD in a tertiary Gastroenterology Department. Diagnosis was based on conventional investigations including small bowel barium contrast radiology (BCR), upper gastrointestinal endoscopy (UGIE), colonoscopy, and endoscopic biopsy (the "gold standards"). IBD was confirmed in 73 (57 Crohn's disease; 10 ulcerative colitis; 6 indeterminate colitis) and excluded in 22 (controls). Scintigraphy was (1) evaluated as a screening test, (2) compared with individual conventional tests, (3) assessed for each gut segment. RESULTS: Screening test: sensitivity 0.75 (95% CI, 0.63-0.85), specificity 0.82 (95% CI, 0.59-0.94), PPV 0.93, NPV 0.5. Comparison with BCR: sensitivity 0.87 (95% CI, 0.72-0.96), specificity 0.57 (95% CI, 0.39-0.73), PPV 0.69, NPV 0.2. Comparison with UGIE: specificity 0.9 (95% CI, 0.79-0.96), NPV 0.13 (sensitivity and PPV unavailable). Comparison with colonoscopy: sensitivity 0.57 (95% CI, 0.41-0.73), specificity 0.71 (95% CI, 0.54-0.85), PPV 0.71, NPV 0.42. Comparison with biopsies paralleled that with endoscopy. False negatives were especially common (NPV< or =0.2) in the proximal gut. CONCLUSIONS: (99m)Tc-HMPAO leukocyte scintigraphy should not be relied on as a screening test for IBD because false negative results are common. This method is especially unreliable at detecting disease in the proximal gut.