Nutritional risk screening-a cross-sectional study in a tertiary pediatric hospital.

BACKGROUND: All hospitalized patients should be screened for malnutrition risk. No universal method exists for pediatric patients. METHODS: We performed a cross-sectional study comparing three published malnutrition risk screening tools (PYMS, STAMP, and STRONGkids), applying them to each inpatient aged 1 month to 17 years over a period of five consecutive weekdays in Helsinki University Hospital, Finland. RESULTS: Of the eligible patients, 67% (n = 69) participated. We found that 6.2% of the children were acutely malnourished and accurately categorized by the three tools. STRONGkids showed the highest specificity (100%) and positive predictive value (36%). Acute malnutrition seemed to be associated with longer hospital stay (p = 0.051). CONCLUSION: STRONGkids was the most accurate screening tool for detecting acute malnutrition and was therefore chosen as the screening method in our hospital. Routine screening for the risk of malnutrition in pediatric inpatients is important in detecting at-risk children who would otherwise be left without dietary intervention.

Malignancy and mortality in paediatric-onset inflammatory bowel disease: a 3-year prospective, multinational study from the paediatric IBD Porto group of ESPGHAN.

BACKGROUND: Risk benefit strategies in managing inflammatory bowel diseases (IBD) are dependent upon understanding the risks of uncontrolled inflammation vs those of treatments. Malignancy and mortality in IBD have been associated with disease-related inflammation and immune suppression, but data are limited due to their rare occurrence. AIM: To identify and describe the most common causes of mortality, types of cancer and previous or current therapy among children and young adults with paediatric-onset IBD. METHODS: Information on paediatric-onset IBD patients diagnosed with malignancy or mortality was prospectively collected via a survey in 25 countries over a 42-month period. Patients were included if death or malignancy occurred after IBD diagnosis but before the age of 26 years. RESULTS: In total, 60 patients were identified including 43 malignancies and 26 fatal cases (9 due to cancer). Main causes of fatality were malignancies (n = 9), IBD or IBD-therapy related nonmalignant causes (n = 10; including 5 infections), and suicides (n = 3). Three cases, all fatal, of hepatosplenic T-cell lymphoma were identified, all were biologic-naïve but thiopurine-exposed. No other haematological malignancies were fatal. The 6 other fatal cancer cases included 3 colorectal adenocarcinomas and 3 cholangiocarcinomas (CCAs). Primary sclerosing cholangitis (PSC) was present in 5 (56%) fatal cancers (1 colorectal carcinoma, 3 CCAs and 1 hepatosplenic T-cell lymphoma). CONCLUSIONS: We report the largest number of paediatric-onset IBD patients with cancer and/or fatal outcomes to date. Malignancies followed by infections were the major causes of mortality. We identified PSC as a significant risk factor for cancer-associated mortality. Disease-related adenocarcinomas were a commoner cause of death than lymphomas.

Declining trend in the incidence of biopsy-verified coeliac disease in the adult population of Finland, 2005-2014.

BACKGROUND: The frequency of coeliac disease (CD) has been on the rise over the past decades, especially in Western Europe, but current trends are unclear. AIM: To research the recent temporal changes in the incidence of adult, biopsy-verified coeliac disease and dermatitis herpetiformis (DH) in Finland, a country with a high frequency of coeliac disease. METHODS: All coeliac disease and DH cases diagnosed at age 20-79 years during 2005-2014 were retrieved from a nationwide database documenting all applicants for monthly compensation to cover the extra cost of maintaining a gluten-free diet. This benefit is granted on the basis of histology, not socioeconomic status. Temporal trends in the annual incidences were estimated using Poisson regression analyses. RESULTS: The total incidence of coeliac disease decreased from 33/100 000 during the years 2005-2006 to 29/100 000 during 2013-2014. The mean annual incidence of coeliac disease was nearly twice as high among women as among men, 42 vs 22 per 100 000, respectively. For middle- and old-aged women, the average rate of decrease in incidence was 4.8% (95% CI 3.9-5.7) per year and for men 3.0% (1.8-4.1) (P for linear trend <.001, for both). Similarly, the annual incidence of DH declined. For young adults, the rate of change remained low and nonsignificant throughout the period 2005-2014. CONCLUSIONS: Although the awareness of coeliac disease has increased during the past decades, the incidence of biopsy-verified diagnoses is not increasing, which suggests that exposure to yet unidentified triggering factors for coeliac disease has plateaued among the Finnish adult population.

C4B gene influences intestinal microbiota through complement activation in patients with paediatric-onset inflammatory bowel disease.

Complement C4 genes are linked to paediatric inflammatory bowel disease (PIBD), but the mechanisms have remained unclear. We examined the influence of C4B gene number on intestinal microbiota and in-vitro serum complement activation by intestinal microbes in PIBD patients. Complement C4A and C4B gene numbers were determined by genomic reverse transcription-polymerase chain reaction (RT-PCR) from 64 patients with PIBD (Crohn's disease or ulcerative colitis). The severity of the disease course was determined from faecal calprotectin levels. Intestinal microbiota was assessed using the HITChip microarray. Complement reactivity in patients was analysed by incubating their sera with Yersinia pseudotuberculosis and Akkermansia muciniphila and determining the levels of C3a and soluble terminal complement complex (SC5b-9) using enzyme immunoassays. The microbiota diversity was wider in patients with no C4B genes than in those with one or two C4B genes, irrespective of intestinal inflammation. C4B and total C4 gene numbers correlated positively with soluble terminal complement complex (TCC, SC5b-9) levels when patient serum samples were stimulated with bacteria. Our results suggest that the C4B gene number associates positively with inflammation in patients with PIBD. Multiple copies of the C4B gene may thus aggravate the IBD-associated dysbiosis through escalated complement reactivity towards the microbiota.

Human leucocyte antigens B*08, DRB1*03 and DRB1*13 are significantly associated with autoimmune liver and biliary diseases in Finnish children.

AIM: The human leucocyte antigen (HLA) allele and haplotype frequencies of the Finnish population are unique because of the restricted and homogenous gene population. There are no published data on HLA genotype associations in paediatric autoimmune liver diseases in Scandinavia. This study characterised the HLA genotypes of children with autoimmune liver or biliary disease in Finland. METHODS: The study cohort comprised 19 paediatric patients (13 female) aged three years to 15 years treated for autoimmune liver or biliary disease at the Children's Hospital, Helsinki University Hospital, between 2000 and 2011, and followed up for four years and three months to 14.6 years. We genotyped HLA-B and HLA-DRB1 in the children, and the HLA antigen frequencies were compared with 19 807 records from the Finnish Bone Marrow Donor Registry. RESULTS: All paediatric patients with autoimmune liver or biliary disease had either autoimmune HLA haplotype B*08;DRB1*03 or DRB1*13. These were significantly more common among patients with autoimmune hepatitis, primary sclerosing cholangitis and autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome than the Finnish control population. HLA RB1*04 was not found in the study cohort. CONCLUSION: Our study found that B*08, DRB1*03 and DRB1*13 were significantly associated with autoimmune liver and biliary diseases in Finnish paediatric patients.

Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease.

Children and adolescents with Crohn's disease (CD) present often with a more complicated disease course compared to adult patients. In addition, the potential impact of CD on growth, pubertal and emotional development of patients underlines the need for a specific management strategy of pediatric-onset CD. To develop the first evidenced based and consensus driven guidelines for pediatric-onset CD an expert panel of 33 IBD specialists was formed after an open call within the European Crohn's and Colitis Organisation and the European Society of Pediatric Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough review of existing evidence a state of the art guidance on the medical treatment and long term management of children and adolescents with CD, with individualized treatment algorithms based on a benefit-risk analysis according to different clinical scenarios. In children and adolescents who did not have finished their growth, exclusive enteral nutrition (EEN) is the induction therapy of first choice due to its excellent safety profile, preferable over corticosteroids, which are equipotential to induce remission. The majority of patients with pediatric-onset CD require immunomodulator based maintenance therapy. The experts discuss several factors potentially predictive for poor disease outcome (such as severe perianal fistulizing disease, severe stricturing/penetrating disease, severe growth retardation, panenteric disease, persistent severe disease despite adequate induction therapy), which may incite to an anti-TNF-based top down approach. These guidelines are intended to give practical (whenever possible evidence-based) answers to (pediatric) gastroenterologists who take care of children and adolescents with CD; they are not meant to be a rule or legal standard, since many different clinical scenario exist requiring treatment strategies not covered by or different from these guidelines.

Rapid test for fecal calprotectin levels in children with Crohn disease.

Assessment of fecal calprotectin, a surrogate marker of mucosal inflammation, is a promising means to monitor therapeutic response in pediatric inflammatory bowel disease, especially if the result is readily available. We tested the performance of a novel calprotectin rapid test, Quantum Blue, versus the conventional enzyme-linked immunosorbent assay in 134 stool samples from 56 pediatric patients with Crohn disease. The intraclass correlation coefficient analysis reflected good agreement (intraclass correlation coefficient 0.97 [95% confidence interval 0.95-0.98]) but agreement was better in lower values, where dilutions were not required. Using a cutoff of 100 µg/g for normal values, the percentage agreement between the 2 tests was 87%. The optimal cutoff values to guide clinical decisions in the therapy of inflammatory bowel disease have yet to be determined.

Magnetic resonance enterography guiding treatment in children with Crohn's jejunoileitis.

AIM: To determine the usefulness of magnetic resonance enterography (MRE) in treatment for paediatric patients with Crohn's disease. METHODS: To evaluate small bowel involvement, 45 children with Crohn's disease were scheduled for MRE. Two radiologists blinded to the patient data independently re-evaluated the images. Findings in images were compared to macroscopic findings at surgery or endoscopy. RESULTS: The terminal ileum was visualized in all with a completed procedure (43/45). The treatment remained conservative in 74% after imaging. In all 13 patients who underwent ileocolonoscopy within 3 months of MRE, the MRE findings were comparable with the macroscopic findings or revealed a more extensive disease. Bowel resection was performed in 26% after imaging. The macroscopic findings in the bowel corresponded to the MRE findings in 73%. In three MRE suggested a more severe disease than was verified intraoperatively. CONCLUSIONS: Magnetic resonance enterography identifies disease involvement in the small bowel in young patients with Crohn's disease and may guide decisions on the need for intestinal surgery or adjustment of medication.

Parent-adolescent agreement on psychosocial symptoms and somatic complaints among adolescents with inflammatory bowel disease.

AIM: To investigate parent-adolescent agreement on psychosocial and somatic symptoms in adolescents with inflammatory bowel disease (IBD). METHODS: A questionnaire-based postal survey comprising Finnish adolescents aged 10-18 years with IBD (n = 156) and their parents. Emotional, behavioural and somatic symptoms were measured using the Child Behaviour Checklist (parent report) and the Youth Self-Report. RESULTS: In paediatric IBD, adolescents and parents agreed on the presence of a psychosocial problem (in subclinical/clinical range) in 5% of the cases but disagreed in 21%. In 74% of the dyads, respondents agreed that no problems existed. Agreement in reporting psychosocial or somatic symptoms was poor to low (κ = 0.00-0.38). The lowest agreement was on anxious/depressed mood (κ = 0.02) and thought problems (κ = 0.00) and the highest on social problems. The parents reported more somatic symptoms in their adolescents than the adolescents themselves (p < 0.001). CONCLUSION: Young IBD patients and their parents disagree in reporting psychosocial and somatic symptoms of the patients. The adolescents as well as their parents need to be involved; otherwise, many symptoms of clinical significance would go unnoticed.

Intra-articular corticoid injection induces circulating glucocorticoid bioactivity and systemic immune activation in juvenile idiopathic arthritis.

OBJECTIVE: To study the systemic effects of intra-articular (IA) glucocorticoid (GC) injections in juvenile idiopathic arthritis (JIA). METHODS: The study group comprised 21 JIA patients being treated with IA methylprednisolone [MP (n = 15) or MP plus triamcinolone hexacetonide (THA) (n = 6)] prescribed on clinical indications. The systemic effect of MP was assessed by measuring circulating glucocorticoid bioactivity (GBA) with a recombinant cell transactivation assay 7 and 24 h after the IA injections, and after 2 months. The systemic immunological responses were studied with a novel assay for testing patient serum-induced changes in the secretion of interferon (IFN)-γ and interleukin (IL)-5 from target cells. RESULTS: Administration of IA GC induced serum GBA (p = 0.001) and suppressed circulating cortisol levels (p = 0.002) 7 h after the injection. Serum withdrawn 24 h after the IA injection induced less IL-5 secretion from mitogen-activated target cells when compared with pre-treatment sera (p = 0.036). This decrease in target cell T helper (Th)2 response (IL-5) was MP dose related (r = -0.550, p = 0.018). High IL-5 secretion from target cells prior to the IA injections was associated with good clinical outcome at 2 months, seen as a low number of active (p = 0.044) and restricted joints (p = 0.049). CONCLUSION: IA GC injections have systemic effects that are reflected in the serum as an immediate elevation of GBA, a decrease of endogenous cortisol as well as a suppressive effect of patient serum on target cell IL-5 secretion. These systemic effects may play a role in the attenuation of disease activity.

Prevention of acute adverse events related to infliximab infusions in pediatric patients.

OBJECTIVE: To study whether premedication with an oral antifebrile agent (acetaminophen) and antihistamine (cetirizine) could decrease the frequency of acute infusion reactions in pediatric patients. METHODS: All pediatric patients scheduled for infliximab infusions at the Helsinki University Central Hospital, a tertiary care center, were prospectively introduced to a standard oral premedication of acetaminophen (20 mg/kg) and cetirizine (10 mg) prior to infliximab infusions for a period of 1 year. All acute adverse events related to infliximab infusions given according to the guidelines of pediatric rheumatologists or gastroenterologists were registered for this time period and retrospectively during the preceding year. RESULTS: During the study period, infliximab infusions with premedication were given to 64 pediatric patients (48 with rheumatic disease and l6 with inflammatory bowel disease, mean age 13 years, n = 34 boys, and n = 30 girls). Infliximab was introduced to 14 children; the rest were on maintenance therapy. Twelve infusion reactions, 4 mild and 8 severe, were observed in 8 (12.5%) of the 64 subjects, and in 1 subject 4 times. During the preceding year, 60 pediatric patients had received infliximab infusions without premedication. In this latter group, infusion reactions occurred in 5 children (8.3%; P > 0.05). The presentation of an acute infusion reaction was not related to the sex or diagnosis of the patient. CONCLUSION: In pediatric patients, acute infusion reactions related to infliximab could not be prevented with premedication with oral acetaminophen and cetirizine.

Clinics of coeliac disease in children in the 2000s.

OBJECTIVE: To describe the clinical picture of patients with coeliac disease (CD) and the change in its presentation over the past decades. STUDY DESIGN: Patients with CD were identified and clinical data collected from hospital records over a 6-year period (2000-2005). RESULTS: Altogether 197 patients aged 0.6-15.9 (mean 7.2) years were identified. They were found amongst the child population served by the hospital, the mean number of children at age 0.5-16 years was 268 000 during 2000-2005. The presenting symptom amongst the youngest patients (<3 years) was chronic diarrhoea (in 67%), and amongst older patients, abdominal pain. At the time of diagnosis, growth was severely retarded (height <2 SD for age) in 6.6%; mean height was -0.06 SD and weight + 1% for height. After diet treatment for a mean of 6 months, both height and weight increased significantly. Anaemia and iron deficiency were present in 25% and 43% of patients respectively. Intraepithelial T-cell receptor gamma/delta cells were pathologic in all 150 specimens studied. CONCLUSIONS: The presentation of CD depends on age. Even when we found six times more patients than during years 1976-1985 in the same hospital, published data on the prevalence of CD suggest that we found only a small minority of children with CD.

Correlation of faecal calprotectin and lactoferrin with an endoscopic score for Crohn's disease and histological findings.

BACKGROUND: Faecal calprotectin and lactoferrin increasingly serve as surrogate markers of disease activity in IBD. Data on the correlation of these markers with simple endoscopic score for Crohn's disease (SES-CD) and with histological findings are as yet limited. Aim To study the correlation of faecal calprotectin and lactoferrin with SES-CD and histology. METHODS: During 87 consecutive ileocolonoscopies, SES-CD was calculated and biopsy specimens were obtained from the ileum, colon and rectum. Faecal calprotectin and lactoferrin were measured. RESULTS: In ileocolonic or colonic disease, both faecal calprotectin and lactoferrin correlated significantly with colon SES-CD (P < 0.001) and colon histology (P < 0.001). In patients with normal calprotectin or lactoferrin levels, endoscopic and histology scores were significantly lower than in those with elevated concentrations (P < 0.001). In ileal CD, ileal SES-CD correlated with histology (P < 0.001), but not with faecal calprotectin (P = 0.161) or lactoferrin (P = 0.448). CONCLUSION: In ileocolonic and colonic disease, endoscopic score SES-CD and histological findings correlated significantly with faecal calprotectin and lactoferrin. A normal faecal-marker concentration was a reliable surrogate marker for endoscopically and histologically inactive CD. Ileal endoscopic score and histological findings failed, however, to correlate with faecal markers.

Severe adverse reactions to Infliximab therapy are common in young children with inflammatory bowel disease.

UNLABELLED: Since 2000 we have introduced 141 Infliximab infusions to 23 children with severe inflammatory bowel disease. A total of seven severe adverse reactions occurred in 26% (6 of 23) of the children. Four reactions were acute (anaphylaxis n = 2; allergic reaction n = 2) and 3/4 of these children were younger than 10 years of age. Two children developed an abscess and one child had septicaemia and brain lesions related to progressive multifocal leucoencephalopathy. CONCLUSION: adverse reactions to Infliximab infusions are common. Young children seem to be prone to severe allergic reactions although they are on azathioprine and conventional glucocorticoid therapy.

A genetic test which can be used to diagnose adult-type hypolactasia in children.

BACKGROUND/AIMS: Adult-type hypolactasia (primary lactose malabsorption) affects most of world's human population and limits the use of fresh milk due to lactose intolerance. The diagnosis of adult-type hypolactasia has been difficult to establish because of unsatisfactory diagnostic methods. C/T(-13910) single nucleotide polymorphism residing 13910 base pairs from the 5' end of the lactase gene has been shown to be associated with lactase persistence. The aim of the study was to assess the applicability of the C/T(-13910) variant as a diagnostic test for adult-type hypolactasia during childhood. METHODS: Intestinal biopsies were obtained from 329 children and adolescents of African, Finnish, and other White origins aged 0.1-20 years undergoing upper gastrointestinal endoscopy because of abdominal complaints. The biopsies were assayed for lactase, sucrase, and maltase activity and genotyped for the C/T(-13910) variant using polymerase chain reaction minisequencing. RESULTS: The frequency of the C/C(-13910) genotype defining lactase non-persistence was well in agreement in this study with published figures for the prevalences of adult-type hypolactasia in Africans and Whites. The C/C(-13910) genotype was associated with very low lactase activity (<10 U/g protein) in the majority of children tested at 8 years of age and in every child older than 12 years of age giving a specificity of 100% and sensitivity of 93% for the genetic test. The decline of lactase activity was somewhat earlier in African compared with Finnish children with C/C(-13910) genotype (p<0.03). CONCLUSIONS: Genetic test of C/T(-13910) polymorphism can be used as a first stage screening test for adult-type hypolactasia.

Dental caries is common in Finnish children infected with Helicobacter pylori.

Childhood factors such as low socioeconomic status are risk factors for Helicobacter pylori infection and Streptococcus mutans-related dental caries. We examined whether H. pylori infection and dental caries are present today in the same group of children examined previously. We reviewed the public dental health service files of 21 H. pylori-positive children (upper gastrointestinal endoscopy at a median age of 13.5 y) and 27 H. pylori-negative children (endoscopy at a median age of 12.5 y) examined during 1995-98 at the Helsinki University Central Hospital, Finland. All H. pylori-positive children had experienced dental caries in their primary or permanent teeth or in both whereas among H. pylori-negative children the respective proportion was 70% (p < 0.01). At the age of 7 y, 18% (3/17) of the H. pylori-positive children had experienced caries in permanent teeth as compared to 0% among H. pylori-negative children (0/24; p < 0.05). At the age of 12 y, H. pylori-positive children had more decayed, missing or filled permanent teeth than H. pylori-negative children (80% vs. 38%; p < 0.05). Although a causal relationship between H. pylori and dental caries is unlikely, it is possible that H. pylori-infected children have an increased risk of other health problems, such as dental caries, for which proper treatment is needed.

cagA, vacA and iceA virulence genes of Helicobacter pylori isolates of children in Finland.

cagA, vacA s and m genotypes and iceA alleles were analyzed from Helicobacter pylori strains isolated from 17 Finnish children and 32 children of non-Finnish origin living in Finland. Twelve children in the latter group were eastern European and 15 were of African origin. Only three children of non-Finnish origin were born in Finland. The vacA sla subtype was more prevalent in the isolates from Finnish children than African children (76% vs. 7%, P<0.001); vacA s1b frequencies were 5% and 67%, respectively (P<0.001). The iceA1 allele was significantly more prevalent in African than Finnish isolates (93% vs. 35%, P< 0.01). Considerable variation was noted in the frequency of vacA s1 subtypes and iceA alleles in children originating from different geographic regions, but the geographic variation of s1 subtypes resembled that described in other reports.

Parietal cell antibodies and Helicobacter pylori in children.

BACKGROUND: Gastric autoantibodies are common in Helicobacter pylori-infected adults, and the presence of these antibodies is associated with atrophic gastritis. The role of H. pylori in the autoimmune type of atrophic gastritis is unresolved, and it is not known at what stage the autoantibodies appear in serum during H. pylori infection. Therefore, we screened children with and without H. pylori infection for gastric parietal cell antibodies. METHODS: Seventy-one children with H. pylori infection verified by examination of gastric biopsy specimens (mean age, 9.4 years), 8 children with positive serology but negative histology for H. pylori (mean age, 11.6 years), and 130 children with negative serology for H. pylori (mean age, 7.7 years) were screened for the presence of gastric parietal cell antibodies in serum by indirect immunofluorescence. In addition, 61 children with celiac disease (mean age, 7.1 years) were screened for gastric parietal cell antibodies and H. pylori antibodies. RESULTS: None of the children with H. pylori infection had gastric parietal cell antibodies in serum. Only three positive parietal cell antibody reactions were found: a 14-year-old boy with positive serology for H. pylori but no other signs of infection (titer 5000), a 14-year-old girl with tuberculosis (titer 1250, seronegative for H. pylori) and a 10-year-old girl with insulin-dependent diabetes mellitus (titer 6250, seronegative for H. pylori). CONCLUSIONS: Although gastric autoantibodies are often found in adults with chronic H. pylori gastritis, it seems that H. pylori-infected children are not positive for gastric parietal cell antibodies. It remains to be studied in which H. pylori infections and at what stages gastric autoantibodies appear.

Ethnic differences in intestinal disaccharidase values in children in Finland.

BACKGROUND: Intestinal disaccharidase activities tend to be low in villous atrophy, but there are only a few reports of enzyme activities in children with normal villous architecture. METHODS: In the current study the data were reviewed on disaccharidase activities in duodenal biopsy specimens of normal villous structure in 223 children undergoing upper gastrointestinal endoscopy in 1997 and 1998. The ancestry was Finnish in 188 children (median age 8.0 years; range, 0.2-18 years), African in 27 children (median age 5.0 years; range, 1-13 years), and other in eight children. RESULTS: The mean activities of lactase, sucrase, and maltase were significantly higher in Finnish children than in children of African origin (P < 0.0001, P < 0.002, and P < 0.02, respectively). Lactase activity decreased with increasing age (P < 0.001), but age had no significant effect on maltase and sucrase activities. Among Finnish children, 31% (59/188) had lactase activity below the established reference range of 20 units (units are micromoles of substrate hydrolyzed per minute at 37 degrees C per gram of protein) and one child had a probable sucrase-isomaltase deficiency. When these 60 children with low enzyme activities were excluded, the geometric means were lactase, 35.7 units (95% confidence interval [CI], 32.8-38.6 units); maltase, 241 units (95% CI, 225-258 units); and sucrase, 57.5 units (95% CI, 53.5-61.6 units). Among the children of African origin, lactase activity was decreased in 67% (18/27). All three enzyme activities were decreased in parallel more often among the African children (8/27) than among the Finnish children (9/188; P < 0.002). CONCLUSIONS: Ethnicity has a strong effect on disaccharidase values in children with normal villous structure. African children have lower activities of lactase, sucrase, and maltase in duodenal specimens than do children of Finnish origin.