Sibylle Koletzko

Ludwig-Maximilian-University of Munich, München, Bavaria, Germany

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Publications (297)1125.65 Total impact

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    ABSTRACT: Patients with a diverse spectrum of rare genetic disorders can present with inflammatory bowel diseases (monogenic IBD). Patients with these disorders often develop symptoms during infancy or early childhood, along with endoscopic or histologic features of Crohn's disease, ulcerative colitis or IBD unclassified. Defects in interleukin 10 signaling have a Mendelian inheritance pattern with complete penetrance of intestinal inflammation. Several genetic defects that disturb intestinal epithelial barrier function or affect innate and adaptive immune function have incomplete penetrance of the IBD-like phenotype. Several of these monogenic conditions do not respond to conventional therapy and are associated with high morbidity and mortality. Due to the broad spectrum of these extremely rare diseases, a correct diagnosis is frequently a challenge and often delayed. In many cases, these diseases cannot be categorized based on standard histologic and immunologic features of IBD. Genetic analysis is required to identify the cause of the disorder and offer the patient appropriate treatment options, which include medical therapy, surgery, or allogeneic hematopoietic stem cell transplantation. In addition, diagnosis based on genetic analysis can lead to genetic counseling for family members of patients. We describe key intestinal, extra-intestinal, and laboratory features of 50 genetic variants associated with IBD-like intestinal inflammation. We provide approaches for identifying patients likely to have these disorders. We discuss classical approaches to identify these variants in patients, starting with phenotypic and functional assessments that lead to analysis of candidate genes. As a complementary approach, we discuss parallel genetic screening using next-generation sequencing followed by functional confirmation of genetic defects.
    Gastroenterology 07/2014; · 12.82 Impact Factor
  • Zeitschrift fur Gastroenterologie. 07/2014; 52(7):711-743.
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    ABSTRACT: AIM: We investigated whether objectively measured access to urban green spaces is associated with behavioural problems in 10-year old children living in Munich and its surrounding areas. METHODS: Behavioural problems were assessed in the GINIplus and LISAplus 10-year follow-up between 2006 and 2009 using the Strengths and Difficulties Questionnaire. Access to green spaces was defined using the distance from a child's residence to the nearest urban green space. Associations between access to urban green spaces and behavioural problems were assessed using proportional odds and logistic regression models in 1932 children with complete exposure, outcome and covariate data. RESULTS: The distance between a child's residence and the nearest urban green space was positively associated with the odds of hyperactivity/inattention, especially among children with abnormal values compared to children with borderline or normal values (odds ratio (OR)=1.20 (95% confidence interval (CI)=1.01-1.42) per 500m increase in distance). When stratified by sex, this association was only statistically significant among males. Children living further than 500m away from urban green spaces had more overall behavioural problems than those living within 500m of urban green spaces (proportional OR=1.41 (95% CI=1.06-1.87)). Behavioural problems were not associated with the distance to forests or with residential surrounding greenness. CONCLUSION: Poor access to urban green spaces was associated with behavioural problems in 10-year old children. Results were most consistent with hyperactivity/inattention problems.
    Environment International 06/2014; 71C:29-35. · 6.25 Impact Factor
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    ABSTRACT: Crohn disease is an inflammatory bowel disease (IBD) with a complex mode of inheritance. Although nucleotide binding and oligomerization domain containing 2 (NOD2) is the strongest risk factor, the cause of Crohn disease remains unknown in the majority of the cases. X-linked inhibitor of apoptosis (XIAP) deficiency causes X-linked lymphoproliferative syndrome type 2. IBD has been reported in some XIAP-deficient patients.
    The Journal of allergy and clinical immunology. 06/2014;
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    ABSTRACT: Although rotavirus (RV) vaccination was licensed in 2006, it was not included into the officially recommended German childhood vaccination schedule until 2013. Local differences in health policies in the past led to large differences in vaccination coverage rate between the federal states of Germany. This enables an ecologic study of RV vaccine effectiveness.
    The Pediatric Infectious Disease Journal 06/2014; · 3.57 Impact Factor
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    ABSTRACT: 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.
    Journal of Crohn's & colitis. 06/2014;
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    ABSTRACT: Positive greenness effects on health are increasingly reported, although studies on allergic outcomes remain limited and conflicting. We examined whether residential greenness is associated with childhood doctor diagnosed allergic rhinitis, eyes and nose symptoms and aeroallergen sensitisation using two combined birth cohorts (GINIplus and LISAplus) followed from birth to 10 years in northern and southern Germany (Ntotal=5803).
    Journal of epidemiology and community health. 05/2014;
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    ABSTRACT: Background/Objectives:Mother's body mass index (BMI) is a strong predictor of child BMI. Whether mother's BMI correlates with child's food intake is unclear. We investigated associations between mother's BMI/overweight and child's food intake using data from two German birth cohorts.Subjects/Methods:Food intakes from 3230 participants were derived from parent-completed food frequency questionnaires. Intakes of 11 food groups were categorized into three levels using group- and sex-specific tertile cutoffs. Mother's BMI and overweight were calculated on the basis of questionnaire data. Multinomial regression models assessed associations between a child's food intake and mother's BMI/overweight. Linear regression models assessed associations between a child's total energy intake and mother's BMI. Models were adjusted for study region, maternal education, child's age, sex, pubertal status and energy intake and the BMIs of the child and father.Results:Mothers' BMI was associated with high meat intake in children (adjusted relative risk ratio (RRR (95% confidence interval))=1.06 (1.03; 1.09)). Mothers' overweight was associated with the meat intake (medium versus low RRR=1.30 (1.07; 1.59); high versus low RRR=1.50 (1.19; 1.89)) and egg intake (medium versus low RRR=1.24 (1.02; 1.50); high versus low RRR=1.30 (1.07; 1.60)) of children. There were no consistent associations for rest of the food groups. For every one-unit increase in mothers' BMI, the total energy intake in children increased by 9.2 kcal (3.7; 14.7). However, this effect was not significant after adjusting for children's BMI.Conclusions:Our results suggest that mother's BMI and mother's overweight are important correlates of a child's intake of energy, meat and eggs.European Journal of Clinical Nutrition advance online publication, 21 May 2014; doi:10.1038/ejcn.2014.92.
    European journal of clinical nutrition. 05/2014;
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    ABSTRACT: According to Ulrich's psychoevolutionary theory, contact with green environments mitigates stress by activating the parasympathetic system, (specifically, by decreasing blood pressure (BP)). Experimental studies have confirmed this biological effect. However, greenness effects on BP have not yet been explored using an observational study design. We assessed whether surrounding residential greenness is associated with BP in 10 year-old German children.
    BMC Public Health 05/2014; 14(1):477. · 2.08 Impact Factor
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    Joachim Heinrich, Berthold Koletzko, Sibylle Koletzko
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    ABSTRACT: The timing of the introduction of complementary foods appears crucial to the development of allergic diseases later in life. The results from recent observational studies might be misinterpreted to suggest that introducing complementary food prior to the age of four months might have a beneficial effect on the induction of immune tolerance. Since these two recently published papers cannot completely account for reverse causation, as is the case for all observational studies, we recommend that the current ESPGHAN and American Academy of Pediatrics recommendations be maintained as long as new evidence from large randomized controlled intervention trials do not suggest otherwise. That is, complementary foods should be first introduced between the age of 17 to 26 weeks.
    Expert Review of Clinical Immunology 05/2014; · 2.89 Impact Factor
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    ABSTRACT: The function of interleukin-37 is not resolved yet. We recently showed that IL-37 suppresses colonic inflammation in mice. To gain more insight into its relevance in human disease, we investigated the expression of IL-37 in the intestine of pediatric patients with chronic inflammatory bowel disease. Intestinal biopsies were obtained from children with inflammatory bowel disease (18 Crohn's disease (CD), 14 ulcerative colitis (UC) and 11 controls) during endoscopy and analyzed for IL-37 expression by immunohistochemistry and real-time PCR. Results were correlated with immunostaining for IL-18 and IL17, mRNA levels of pro- and anti-inflammatory cytokines and clinical parameters. IL-37 protein was detected in epithelial cells and submucosal lymphoid cells of CD and UC patients as well as healthy controls. IL-37 protein expression tended to be higher with submucosal lymphoid cell infiltration of patients with CD and UC and correlated with histological severity score of inflammation. IL-18 showed a similar staining pattern to IL-37, whereas staining for IL-17 revealed distinct positive cells scattered in the submucosal layer. Messenger RNA-expression of IL-8, IL-17 and IL-10 was up-regulated in CD and UC patients. mRNA-levels of IL-18 and IL-37 were not significantly elevated compared to controls. Levels of IL-37 and IL-18 mRNA showed a positive correlation in the CD group. IL-37 protein is expressed in healthy and diseased bowel tissue. IL-37 and IL-18 show a similar expression pattern and correlate at mRNA levels. Future studies are warranted to delineate the specific contribution of IL-37 to modulate chronic bowel inflammation in humans.
    Journal of pediatric gastroenterology and nutrition 04/2014; · 2.18 Impact Factor
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    ABSTRACT: Background Exclusive enteral nutrition (EEN) induces remission and mucosal healing in children with active Crohn's disease (CD).AimTo compare short- and long-term outcomes of the first vs. second courses of EEN, and to identify predictors of sustained remission.Methods Retrospective single centre analysis of all patients with CD (6–18 years) treated with EEN over 7.5 years. Patients were excluded if exposed to anti-TNFα or corticosteroids 3 months prior to EEN. Data included disease phenotype, activity, NOD2 genotype, laboratory indices and anthropometrics. Remission and relapse were defined by mathematically weighted Paediatric Crohn's Disease Activity Index (wPCDAI) with 1-year follow-up.ResultsOf 94 patients treated with EEN, 52 fulfilled inclusion criteria (31 male, mean age 13.2 years). Azathioprine was started within the first month in 33/52 patients; 26/52 received a second EEN course. First compared to second EEN revealed higher wPCDAI at start (59 vs. 40, P < 0.0001), tended to higher remission rates after 3 months (92% vs. 77%, n.s.), but showed comparable 1-year relapse rates (67% vs. 70%, median time 231 vs. 145 days, n.s.). Disease activity, weight gain and inflammatory markers showed better improvement with first EEN. Faecal calprotectin >200 μg/g during EEN was associated with shorter remission (median time 157 vs. 287 days, n.s.). Certain NOD2 genotypes were related to higher relapse rates (92% R702W or G908R vs. 50% 1007fs vs. 60% wild-type, P < 0.01).Conclusions Exclusive enteral nutrition induces remission in active Crohn's disease, but efficacy tends to decrease with the second course. Despite early azathioprine use, 1-year relapse rates are high, but may be related to NOD2 genotype.
    Alimentary Pharmacology & Therapeutics 04/2014; · 4.55 Impact Factor
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    ABSTRACT: Patient satisfaction is a relevant prognostic factor in young persons with chronic disease and may be both age and disease specific. To assess health care quality from the patient's view in young persons with inflammatory bowel disease, an easy to use, valid, reliable and informative specific instrument was needed. All parts of the study were directed at persons with inflammatory bowel disease aged 15 to 24 ([double low-9 quotation mark]youth"). A qualitative internet patient survey was used to generate items, complemented by a physician survey and literature search. A 2nd internet survey served to reduce items based on perceived importance and representativeness. Following pilot testing to assess ease of use and face validity, 150 respondents to a postal survey in patients from a paediatric clinical registry were included for validation analyses. Construct validity was assessed by relating summary scores to results from global questions on satisfaction with care using ANOVA. To assess test-retest reliability using intraclass correlation coefficients (ICC), a subset of patients were assessed twice within 3 months. 302 persons with IBD and 55 physicians participated in the item generating internet survey, resulting in 3,954 statements. After discarding redundancies 256 statements were presented in the 2nd internet survey. Of these, 32 items were retained. The resulting instrument assesses both the perceived relevance (importance) of an item as well as the performance of the care giver for each item for calculation of a summary satisfaction score (range 0 to 1). Sensibility testing showed good acceptance for most items. Construct validity was good, with mean scores of 0.63 (0.50 to 0.76), 0.71 (0.69 to 0.74) and 0.81 (0.79 to 0.83) for no, some and good global satisfaction (ANOVA, p < 0.001). Test-retest reliability was satisfactory (ICC 0.6 to 0.7). We developed an easy to use, patient oriented, valid instrument to assess satisfaction with care in young persons with IBD for use in survey research.
    BMC Health Services Research 03/2014; 14(1):97. · 1.77 Impact Factor
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    ABSTRACT: Loss-of-function mutations in IL10 and IL10R cause very early onset inflammatory bowel disease (VEO-IBD). Here, we investigated the molecular pathomechanism of a novel intronic IL10RA mutation and describe a new therapeutic approach of T cell replete haploidentical hematopoietic stem cell transplantation (HSCT). Clinical data were collected by chart review. Genotypes of IL10 and IL10R genes were determined by Sanger sequencing. Expression and function of mutated IL-10R1 were assessed by quantitative PCR, Western blot analysis, enzyme-linked immunosorbent assays, confocal microscopy, and flow cytometry. We identified a novel homozygous point mutation in intron 3 of the IL10RA (c.368-10C > G) in three related children with VEO-IBD. Bioinformatical analysis predicted an additional 3' splice site created by the mutation. Quantitative PCR analysis showed normal mRNA expression of mutated IL10RA. Sequencing of the patient's cDNA revealed an insertion of the last nine nucleotides of intron 3 as a result of aberrant splicing. Structure-based modeling suggested misfolding of mutated IL-10R1. Western blot analysis demonstrated a different N-linked glycosylation pattern of mutated protein. Immunofluorescence and FACS analysis revealed impaired expression of mutated IL-10R1 at the plasma membrane. In the absence of HLA-identical donors, T cell replete haploidentical HSCT was successfully performed in two patients. Our findings expand the spectrum of IL10R mutations in VEO-IBD and emphasize the need for genetic diagnosis of mutations in conserved non-coding sequences of candidate genes. Transplantation of haploidentical stem cells represents a curative therapy in IL-10R-deficient patients, but may be complicated by non-engraftment.
    Journal of Clinical Immunology 02/2014; · 3.38 Impact Factor
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    ABSTRACT: The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006-2011. We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0-14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein-Barr virus-associated lymphomas. Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.
    Inflammatory Bowel Diseases 02/2014; 20(2):291-300. · 5.12 Impact Factor
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    ABSTRACT: Eczema, rhinitis, and asthma often coexist (comorbidity) in children, but the proportion of comorbidity not attributable to either chance or the role of IgE sensitisation is unknown. We assessed these factors in children aged 4-8 years. In this prospective cohort study, we assessed children from 12 ongoing European birth cohort studies participating in MeDALL (Mechanisms of the Development of ALLergy). We recorded current eczema, rhinitis, and asthma from questionnaires and serum-specific IgE to six allergens. Comorbidity of eczema, rhinitis, and asthma was defined as coexistence of two or three diseases in the same child. We estimated relative and absolute excess comorbidity by comparing observed and expected occurrence of diseases at 4 years and 8 years. We did a longitudinal analysis using log-linear models of the relation between disease at age 4 years and comorbidity at age 8 years. We assessed 16 147 children aged 4 years and 11 080 aged 8 years in cross-sectional analyses. The absolute excess of any comorbidity was 1·6% for children aged 4 years and 2·2% for children aged 8 years; 44% of the observed comorbidity at age 4 years and 50·0% at age 8 years was not a result of chance. Children with comorbidities at 4 years had an increased risk of having comorbidity at 8 years. The relative risk of any cormorbidity at age 8 years ranged from 36·2 (95% CI 26·8-48·8) for children with rhinitis and eczema at age 4 years to 63·5 (95% CI 51·7-78·1) for children with asthma, rhinitis, and eczema at age 4 years. We did longitudinal assessment of 10 107 children with data at both ages. Children with comorbidities at 4 years without IgE sensitisation had higher relative risks of comorbidity at 8 years than did children who were sensitised to IgE. For children without comorbidity at age 4 years, 38% of the comorbidity at age 8 years was attributable to the presence of IgE sensitisation at age 4 years. Coexistence of eczema, rhinitis, and asthma in the same child is more common than expected by chance alone-both in the presence and absence of IgE sensitisation-suggesting that these diseases share causal mechanisms. Although IgE sensitisation is independently associated with excess comorbidity of eczema, rhinitis, and asthma, its presence accounted only for 38% of comorbidity, suggesting that IgE sensitisation can no longer be considered the dominant causal mechanism of comorbidity for these diseases. EU Seventh Framework Programme.
    The lancet. Respiratory medicine. 02/2014; 2(2):131-40.
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    ABSTRACT: This position statement summarises a view of academia regarding standards for clinical research in collaboration with commercial enterprises, focussing on trials in pregnant women, breastfeeding women and children. It is based on a review of the available literature and an expert workshop co-sponsored by the Early Nutrition Academy and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. Clinical research collaborations between academic investigators and commercial enterprises are encouraged by universities, public funding agencies and governmental organisations. One reason is a pressing need to obtain evidence on the effects, safety and benefits of drugs and other commercial products and services. However, the credibility and value of results obtained through public private research collaborations have been questioned, since many examples of inappropriate research practice have become known. Clinical research in pregnant and breastfeeding women, and in infants and children, raise sensitive scientific, ethical and societal questions and require the application of particularly high standards. Here we provide recommendations for the conduct of public private research collaborations in these populations. In the interest of all stakeholders these recommendations should contribute to more reliable, credible and acceptable results of commercially sponsored trials and to reducing the existing credibility gap.
    Journal of pediatric gastroenterology and nutrition 01/2014; · 2.18 Impact Factor
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    ABSTRACT: Robust evaluation of induction therapies using both clinical and inflammatory outcomes in pediatric Crohn's disease (CD) are sparse. We attempted to evaluate clinical, inflammatory, and composite outcomes of induction of remission therapies (normal C reactive protein [CRP] remission) in a large pediatric prospective multicenter study. Patients enrolled at diagnosis into the growth relapse and outcomes with therapy in Crohn's disease study were evaluated for disease activity, CRP, and fecal calprotectin at 8, 12 and 52 weeks after starting treatment. The primary endpoint was week-12 steroid-free remission defined by pediatric Crohn's disease activity index and CRP <0.5 mg/dL. The protocol required tapering off corticosteroids by week 11. We analyzed 222 patients (mean age, 12.9 ± 3.2 yr) main evaluated treatment options included: 5-ASA (n = 29), exclusive enteral nutrition (n = 43), and corticosteroids (n = 114). Clinical remission at week 12 was achieved in 155 (73%) patients; both exclusive enteral nutrition and steroids were associated with normal CRP remission at week 12, although in a post hoc subgroup analysis exclusive enteral nutrition was superior in mild-to-moderate disease for this outcome. Among those in steroid-free remission in week 12, normal CRP predicted 1-year sustained remission (86% for normal CRP versus 61% for elevated CRP; P = 0.02). Baseline severity and early immunomodulation were similar in both groups. Normal CRP steroid-free remission at week 12 was impacted by type of induction therapy, but not by early immunomodulation. It was associated with more corticosteroids-free remission at week 52 and a trend for less relapses.
    Inflammatory Bowel Diseases 01/2014; · 5.12 Impact Factor
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    ABSTRACT: Objective To investigate whether birth by cesarean delivery rather than vaginal delivery is a risk factor for later childhood obesity. Study design Healthy, full-term infants were recruited. Overweight and obesity were defined using measured weight and height according to World Health Organization reference data. Associations between cesarean delivery and being overweight or obese were investigated at age 2, 6, and 10 years (n = 1734, 1244, and 1170, respectively) by multivariate logistic regression models adjusted for socioeconomic status, child characteristics, and maternal prepregnancy characteristics. Results Mothers who gave birth by cesarean delivery (∼17%) had a higher mean prepregnancy body mass index (23.7 kg/m2 vs 22.5 kg/m2), greater mean gestational weight gain (15.3 kg vs 14.5 kg), and shorter mean duration of exclusive breastfeeding (3.4 months vs 3.8 months) compared with those who delivered vaginally. The proportion of obese children was greater in the cesarean delivery group compared with the vaginal delivery group at age 2 years (13.6% vs 8.3%), but not at older ages. Regression analyses revealed a greater likelihood of obesity at age 2 years in the cesarean delivery group compared with the vaginal delivery group at age 2 years (aOR, 1.68; 95% CI, 1.10-2.58), but not at age 6 years (aOR, 1.49; 95% CI, 0.55-4.05) or age 10 years (aOR, 1.16; 95% CI, 0.59-2.29). Conclusion Cesarean delivery may increase the risk of obesity in early childhood. Our results do not support the hypothesis that an increasing rate of cesarean delivery contributes to obesity in childhood.
    The Journal of pediatrics 01/2014; · 4.02 Impact Factor
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    ABSTRACT: Faecal calprotectin is used as a sensitive marker for gastrointestinal mucosal inflammation. We compared the performance of three different assays in a large cohort of symptomatic paediatric patients. Retrospective monocentric study. Inpatients and outpatients of a tertiary referral centre for paediatric gastroenterology. 304 symptomatic patients (163 males, aged 2-20 years) with active inflammatory bowel disease (IBD/A, n=130), IBD in clinical remission (IBD/R, n=62), other intestinal diseases (n=45) and controls without identified intestinal disease (n=67). Calprotectin was measured in homogenised faecal samples with three tests (A: EliA Calprotectin, Phadia AB, Sweden; B: PhiCal, Calpro AS, Norway; C: EK-Cal, Bühlmann Laboratories, Switzerland). Concordance between tests was calculated using Kendall's τ coefficient. IBD/A and controls were correctly classified as 97.7%/82.1% (A), 97.7%/85.1% (B) and 98.4%/62.7% (C; not significant). Test C tended to have higher calprotectin values with a lower specificity compared to tests A and B. The concordance between two tests was 0.835 for tests A and B, 0.782 for tests A and C and 0.765 for tests B and C. All three tests are very sensitive for detecting mucosal inflammation, but major differences exist between specificity and absolute values. It is highly advisable to use the test of the same manufacturer for follow-up and to monitor for disease activity.
    BMJ Open 01/2014; 4(5):e004558. · 1.58 Impact Factor

Publication Stats

5k Citations
1,125.65 Total Impact Points

Institutions

  • 1998–2014
    • Ludwig-Maximilian-University of Munich
      • • Children in the Department of Surgery, Dr. von Hauner Children's Hospital
      • • Department of Epidemiology
      • • Institute for Strategic Management
      • • Children's Hospital and Children clinic at the Dr. von Hauner Children's Hospital
      München, Bavaria, Germany
  • 2013
    • University of Groningen
      Groningen, Groningen, Netherlands
  • 2008–2013
    • Helmholtz-Zentrum für Umweltforschung
      • Department Umweltimmunologie
      Leipzig, Saxony, Germany
    • St. Marien- und St. Annastiftskrankenhaus
      Ludwigshafen, Rheinland-Pfalz, Germany
  • 2003–2013
    • Marien-Hospital Wesel
      Wesel, North Rhine-Westphalia, Germany
    • Pathologisches Institut Bremerhaven
      Bremerhaven, Bremen, Germany
  • 2012
    • Medical University of Warsaw
      Warszawa, Masovian Voivodeship, Poland
    • Odense University Hospital
      Odense, South Denmark, Denmark
  • 2009–2012
    • Helmholtz Zentrum München
      • Institute of Epidemiology II
      München, Bavaria, Germany
    • University of Wuerzburg
      • Department of Internal Medicine II
      Würzburg, Bavaria, Germany
    • Emory University
      • Department of Pathology and Laboratory Medicine
      Atlanta, GA, United States
  • 1995–2012
    • University Hospital München
      München, Bavaria, Germany
  • 2011
    • Hospital Universitari i Politècnic la Fe
      Valenza, Valencia, Spain
  • 2010
    • Leiden University Medical Centre
      Leyden, South Holland, Netherlands
    • Technische Universität Dresden
      Dresden, Saxony, Germany
  • 2009–2010
    • Technische Universität München
      München, Bavaria, Germany
  • 1989–2010
    • University of Toronto
      • • Hospital for Sick Children
      • • Department of Paediatrics
      Toronto, Ontario, Canada
  • 2006
    • University of Southampton
      • Institute of Human Nutrition
      Southampton, ENG, United Kingdom
  • 1983–1993
    • Heinrich-Heine-Universität Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1990
    • SickKids
      Toronto, Ontario, Canada