Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark. Electronic address: firstname.lastname@example.org.
The intestinal microbiota is believed to be involved in the pathogenesis of celiac disease, in addition to genetic variants and dietary gluten. The gut microbiota is strongly influenced by systemic antibiotics-especially in early life. We explored the association between exposure to a systemic antibiotic in the first year of life and risk of diagnosed celiac disease.
We performed an observational nationwide register-based cohort study. We included all children born in Denmark from 1995 through 2012 or Norway from 2004 through 2012. Children born in Denmark were followed until May 8, 2015 (age at end of follow-up was 2.3-20.3 years) and children born in Norway were followed until December 31, 2013 (age at end of follow-up was 1-10 years). We collected medical information from more than 1.7 million children, including 3346 with a diagnosis of celiac disease. Exposure to systemic antibiotics was defined as a dispensed systemic antibiotic in the first year of life.
Exposure to systemic antibiotics in the first year of life was positively associated with diagnosed celiac disease in the Danish and Norwegian cohorts (pooled odds ratio 1.26, 95% confidence interval 1.16-1.36). We found a dose-dependent relation between an increasing number of dispensed antibiotics and the risk of celiac disease (pooled odds ratio for each additional dispensed antibiotic 1.08, 95% confidence interval 1.05-1.11). No specific type of antibiotic or age period within the first year of life was prominent. Adjustment for hospital admissions with an infectious disease in the first year of life did not change the estimates; adjustment for the number of maternally reported infections in the child in 2 large sub-cohorts decreased the association slightly (pooled odds ratio 1.18, 95% confidence interval 0.98-1.39).
In a nationwide study of children in Denmark and Norway, we found exposure to systemic antibiotics in the first year of life to be associated with a later diagnosis of celiac disease. These findings indicate that childhood exposure to systemic antibiotics could be a risk factor for celiac disease.
Many phthalates, parabens and phenols are suspected to have endocrine-disrupting properties in humans. They are found in consumer products, including food wrapping, cosmetics and building materials. The foetus is particularly vulnerable and exposure to these chemicals therefore is of concern for pregnant women. We investigated current exposure to several commonly used phthalates, parabens and phenols in healthy, pregnant Danish women. A total of 200 spot urine samples were collected between 8 and 30 weeks of gestation and analysed for metabolites of ten phenols, seven parabens and 16 phthalate by liquid chromatography-tandem mass spectrometry representing 26 non-persistent compounds. The majority of analytes were present in the urine sample collected from most women who participated. Thus, in 174 of the 200 women, metabolites of more than 13 (>50%) of 26 compounds were detected simultaneously. The number of compounds detected per woman (either as the parent compound or its metabolite(s)) ranged from 7 to 21 with a median of 16. The majority of compounds correlated positively with each other within and between chemical groups, suggesting combined exposure sources. Estimated daily intakes (DIs) of phthalates and bisphenol A (BPA) were below their individual tolerable DI (TDI) and with hazard quotients below 1. In conclusion, we found detectable levels of phthalate metabolites, parabens and phenols in almost all pregnant women, suggesting combined multiple exposures. Although the estimated DI of phthalates and BPA for an individual was below TDI, our results still raise concern, as current toxicological risk assessments in humans do not take into account simultaneous exposure. The true cumulative risk for the foetus may therefore be underestimated.
To evaluate the effect of two intervention modalities concerning overweight and obesity among children in general practice.
Prospective randomized controlled trial.
A total of 60 general practices in the former County of Funen, Denmark.
Overweight children, identified by International Obesity Task Force criteria, aged 5-9 years.
Model 1 with health consultations in general practice during a two-year period or Model 2, an educational programme for the children and their families in addition to the health consultations.
Change in body mass index (BMI) z-score in order to compare the results, independent of gender- and age-related changes over time.
A total of 80 children were recruited with 35 and 45 children allocated to Model 1 and Model 2, respectively. No significant differences were found in the change in BMI z-score (SDS) between the two groups. A decrease in the mean BMI z-score from baseline to study end of -0.20 (95%CI -0.38 to -0.01) in Model 1 and -0.26 (95%CI -0.44 to -0.09) in Model 2, respectively, was detected. The majority of the participants (2/3) continued in the study for more than one year in both models, with a mean of 12 consultations in general practice.
In this particular setting the two intervention strategies against overweight and obesity did not differ significantly with regard to change in BMI z-scores.
Cites: BMC Fam Pract. 2007;8:5017767720
Cites: Int J Pediatr Obes. 2006;1(1):11-2517902211
*Hans Christian Andersen Children's Hospital, Denmark daggerGastrointestinal Motility Laboratory, Denmark double daggerDepartment of Pathology, Denmark section signAllergy Center, Odense University Hospital and University of Southern Denmark
Department of Paediatrics, Esbjerg Hospital, Esbjerg, Denmark paragraph signDepartment of Paediatrics, Sonderborg Hospital, Sonderborg, Denmark #Department of Paediatrics, Kolding Hospital, Kolding, Denmark.
OBJECTIVE:: Eosinophilic oesophagitis (EE) is a clinical entity characterised by a set of symptoms and eosinophilic infiltration of the oesophageal epithelium. Recent reports indicate that EE is increasingly diagnosed in paediatric patients. We aimed to evaluate the epidemiology of paediatric EE in a European population. DESIGN:: Infants and children in the Region of Southern Denmark were prospectively referred for further evaluation of symptoms of gastroesophageal reflux disease (GERD) after treatment failure with a proton pump inhibitor. The evaluation included endoscopy, 24-hour oesophageal pH-metry, histology of oesophageal biopsies, and investigations for food allergy (double-blind, placebo-controlled food challenge, skin prick test, S-IgE antibodies, atopy patch test). RESULTS:: Of the 78 referred patients, 28 qualified for a diagnosis of GERD. Six children had >15 eosinophils per high-power field in biopsies from the oesophageal mucosa and qualified for the diagnosis of EE. The median age at diagnosis was 9.6 years. In 4 of the 6 patients, food allergy was confirmed by double-blind, placebo-controlled food challenge. In the Region of Southern Denmark with a paediatric population of 256,164 between 0 and 16 years of age, a yearly incidence of EE of 0.16/10,000 was estimated. CONCLUSION:: We report a European prospective study of EE. It was documented in 6 of 78 patients with symptoms of GERD corresponding to an annual incidence of 0.16/10,000 infants and children.
Celiac disease (CD) is a chronic inflammatory disease requiring constant management with a gluten-free diet (GFD). Little is known about how CD impacts on health-related quality of life (HRQOL) in children and adolescents, and how they feel about and cope with CD and GFD. This qualitative study explores the impact of CD and GFD on HRQOL in everyday living of children and adolescents.
In focus group interviews, we investigated HRQOL in children and adolescents with CD in order to identify patient concerns in living with CD and on a GFD. Seven focus groups were formed with 23 children/adolescents and 3 parents. Interviews were transcribed verbatim. Grounded theory approach was applied to analyse the interviews.
CD had varying impact on the children and adolescents HRQOL. Two major categories emerged with importance for HRQOL in children and adolescents with CD, having CD (constructed from the six subcategories: symptoms, the diagnosis-process, self-perception, awareness of CD, social and emotional impact of CD, and thoughts about the future) and coping with CD (constructed from the two subcategories: coping with food and coping with social situations). The complexity of coping with CD in social situations that involve food is presented in a flowchart.
Children and adolescents showed large diversity in how much impact CD has on their HRQOL. Different ways of coping with CD and GFD were identified. Findings will be used to generate a patient-driven disease-specific questionnaire to measure HRQOL in children and adolescents with CD.
During the last decades neonatal outcomes for children born with gastroschisis have improved significantly. Survival rates >90% have been reported. Early prenatal diagnosis and increased survival enforce the need for valid data for long-term outcome in the pre- and postnatal counseling of parents with a child with gastroschisis.
Long-term follow-up on all newborns with gastroschisis at Odense University Hospital (OUH) from January 1 1997-December 31 2009. Follow-up included neonatal chart review for neonatal background factors, including whether a GORE(®)DUALMESH was used for staged closure, electronic questionnaires, interview and laboratory investigations. Cases were divided into complex and simple cases according to the definition by Molik et al. (2001). Survival status was determined by the national personal identification number registry. Because of the consistency of the registration, survival status was obtained from all children participating in the study.
A total of 71 infants (7 complex and 64 simple) were included. Overall seven out of the 71 children (9.9%, median age: 52days (25-75% percentile 0-978days) had died at the time of follow-up. Three died during the neonatal period and four died after the neonatal period. Parenteral nutrition (PN) induced liver failure and suspected adhesive small bowel obstruction were the causes of deaths after the neonatal period. Overall mortality was high in the "complex" group compared to the simple group (3/7 (42.9%) vs 4/64 (6.3%), p = 0.04). Forty (62.5%) of the surviving children consented to participate in the follow-up. A total of 12 children had had suspected adhesive small bowel obstruction. Prevalence of small bowel obstruction was not related to the number of operations needed for neonatal closure of the defect. Staged closure was done in 5/12 (41.7%) who developed small bowel obstruction vs 11/35 (31.43%) without small bowel obstruction, p=0.518. A GORE(®)DUALMESH was used in 16 children (22.5%). Of these 2 were complex and 14 were simple cases. Prevalence of recurrent abdominal pain was 22.5% (9/40) among children with gastroschisis compared to 12% in a study on Danish school children, p=0.068. Gastrointestinal symptoms had led to hospital admission after primary discharge in significantly more children with gastroschisis 16 (40.0%) than children younger than 16years old in the general Danish population 129.419/1.081.542 (12.0%), p=0.000. Fecal calprotectin level was above the reference level (>50mg/kg) in 6/16 (37.5%) children >8years old with gastroschisis compared to 1/7 (14.3%) healthy children. (Fisher's exact=0.366). Only 8/38 (21.1%) children with gastroschisis reported to have an umbilicus.
Mortality among children with gastroschisis is still significant with the highest risk among complicated cases. The majority of the deaths is potentially preventable as PN-related causes and suspected adhesive small bowel obstruction counted for five of seven deaths. Neither categorization upon method of abdominal wall closure nor categorization into simple and complex cases can predict the risk of adhesive small bowel obstruction. With improved administration of PN and timely information and attention to the risk of the small bowel obstruction there is good possibility that the associated mortality could decrease. Type of study and level of evidence: Prognosis study, level II.
Several non-persistent industrial chemicals have shown endocrine disrupting effects in animal studies and are suspected to be involved in human reproductive disorders. Among the non-persistent chemicals that have been discussed intensively during the past years are phthalates, bisphenol A (BPA), triclosan (TCS), and parabens because of their anti-androgenic and/or estrogenic effects. Phthalates are plasticizers used in numerous industrial products. Bisphenol A is the main component of polycarbonate plastics and epoxy resins. Parabens and TCS are antimicrobial preservatives and other phenols such as benzophenone-3 (BP-3) act as a UV-screener, while chlorophenols and phenyl phenols are used as pesticides and fungicides in agriculture. In spite of the widespread use of industrial chemicals, knowledge of exposure sources and human biomonitoring studies among different segments of the population is very limited. In Denmark, we have no survey programs for non-persistent environmental chemicals, unlike some countries such as the USA (NHANES) and Germany (GerES). However, we have analyzed the excretion of seven parabens, nine phenols, and the metabolites of eight different phthalates in urine samples collected over the past 6 years from four Danish cohorts. Here, we present biomonitoring data on more than 3600 Danish children, adolescents, young men, and pregnant women from the general population. Our study shows that nearly all Danes were exposed to the six most common phthalates, to BPA, TCS, and BP-3, and to at least two of the parabens. The exposure to other non-persistent chemicals was also widespread. Our data indicate decreasing excretion of two common phthalates (di-n-butyl phthalate and di-(2-ethylhexyl) phthalate) over time.
The impact on children's bone health of a school-based physical education program and participation in leisure time sports: the Childhood Health, Activity and Motor Performance School (the CHAMPS) study, Denmark.
To evaluate the effect of a school based physical education (PE) program and the amount of leisure time sport (LTS) on children's bone health and to examine if LTS influences the impact of school type on children's bone health.
Children attending "sports" schools (6 × 45 min PE lessons per week) were compared to children at "traditional" schools (2 × 45 min of PE lessons per week) in Svendborg, Denmark. Whole-body DXA scans were performed at baseline (2008) and at a two-year follow-up (2010). Bone mineral content (BMC), bone mineral density (BMD), and bone area (BA) were measured. Multilevel regression analyses examined the impact of school type and LTS participation on bone.
742/800 (93%) invited children accepted to participate. 682/742 (92%) participated at two-year follow-up. Mean (SD) age was 9.5 years (0.9) at baseline. A positive association between LTS and BMC, BMD (p
.Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense C, Denmark .Department of Pathology, Odense University Hospital, Odense C, Denmark .Department of Clinical Immunology, Odense University Hospital, Odense C, Denmark .Research Unit of General Practice, Institute of Public Health, University of Southern Denmark, Odense C, Denmark.
Aim: To determine the prevalence and incidence of diagnosed coeliac disease (CD) in Danish children and adolescents and to describe trends over time. Methods: All children with a CD diagnosis registered in the Danish National Patient Registry (DNPR) were included in the study. Data were validated by combining this information with registrations of small-bowel biopsies in the National Registry of Pathology (NRP) and with a selected sample of hospital records. Results: Data were obtained from 1996 to 2010. The prevalence of CD registered in DNPR increased from 43.2 [95% CI 39.3-47.1] to 83.6 [95% CI 78.4-88.7] per 100 000, and the incidence increased from 2.8 [95% CI 1.9-3.9] to 10.0 [95% CI 8.4-12.0] per 100 000; 56% of the children had at least one biopsy compatible with CD registered in NRP. The incidence of biopsy-verified CD increased from 0.8 [95% CI 0.3-1.4] to 6.9 [95% CI 5.4-8.4] per 100 000. The mean age at diagnosis increased from 5.1 [95% CI 3.5-6.6] to 8.1 [95% CI 7.2-9.0] years of age. The proportion of children with associated diseases did not change over time. Conclusion: The prevalence of diagnosed CD in Danish children and adolescents has increased over the last 15 years.
AIM: The aim was to evaluate the pattern of responsiveness and to monitor side effects of episodic administration of infliximab in children with active Crohn's disease (CD) treated in Denmark from 1999 to 2003. MATERIAL AND METHODS: The National Danish Crohn Colitis Database of infliximab was used to identify all Danish CD patients treated at pediatric departments with infliximab. The clinical outcome was assessed by pattern recognition of the disease course 30 days after the first infliximab infusion and 90 days after intended end of treatment. RESULTS: During a 3 year period, infliximab was given to 24 CD patients (9 male/15 female) aged median 15.4 (range 9.8-18.6) years with a median disease duration of 26 (range 0.7-93) months and a median number of infusions of 6 (range 2-11). Five milligrams of infliximab per kilogram infusions were given intravenously. Immediate response was as follows: 8 (33%) patients achieved complete response (CR), 10 (42%) partial response (PR), and 6 (25%) no response (NR). Long-term response was as follows: 7 (29%) patients achieved prolonged response (PRO), defined as maintenance of CR or PR, 10 (42%) were infliximab dependent (ID), defined as relapse of symptoms requiring reinfusions of infliximab to regain CR or PR, and 6 (25%) had NR. Six (25%) patients needed surgery during or after treatment with infliximab. Side effects were seen in four (17%) patients. No serious events were noted. CONCLUSION: Seventy-one percent of the children appeared to benefit (PRO or ID) from infliximab treatment with minor side effects when given episodically. Among these patients, two response patterns were recognized: PRO after ending infliximab treatment (29%) or dependency on reinfusions of infliximab (42%).