Childhood-onset inflammatory bowel disease-health care use, impact on growth and school achievements

The aim of this thesis was to explore the Impact of Inflammatory bowel disease (IBD) on growth and school achievements. We also assessed the Incidence and health care use of patients with very early-onset IBD (VEO-IBD). Furthermore, we examined the validity of register-based definitions of IBD and its subtypes in children. In study 1, we investigated whether patients with childhood-onset IBD are at an increased risk of poorer final grade point average (GPA) at the end of compulsory school (ninth grade) and not qualifying for high school. We identified 2827 children with IBD in National Patient Register (NPR) between 1990 -2014 and compared their final grades obtained from School Register with matched reference individuals and IBD-free siblings. We adjusted for potential confounders, such as parental psychosocial problems and education. We found a statistically significantly lower GPA (adjusted mean grade difference [AMGD] −4.9, 95% CI −7.1 to −2.6, standardised mean difference [SMD] −0.08, 95% CI −0.11 to −0.04) compared to reference individuals though the difference was minimal. Children with IBD did not have an increased risk of not qualifying for high school compared to their siblings or reference individuals (OR 1.14, 95% CI 0.99 to 1.31). In addition, we found that IBD children with markers of longstanding and severe disease underperformed more commonly compared to reference individuals and IBD-free siblings. In study 2, we studied the attained final height and growth retardation in patients with childhood-onset IBD compared to matched reference individuals and their IBD-free full biological siblings using information from the National Patient Register and Pass Register.Analyses were adjusted for potential confounders, including birth order, number of siblings, parental height, parental mental health problems, and education. The adjusted analysis demonstrated that patients with IBD attained a statistically significant shorter final height in adult age (adjusted mean height difference (AMHD) -0.9 cm, 95% CI -1.1 to -0.7) compared to reference individuals and IBD-free full siblings (AMHD-0,8 CM, 95% CI -1.0 to-0.6). Differences in adult mean heights were more prominent in patients with IBD onset before puberty (AMHD -1.6 cm, 95% CI -2.0 to-1.2) than in patients with onset during or after puberty (AMHD-0.8 cm, 95% CI -0.9 to-0.6) and in the subsets of patients exposed to bowel surgery (AMHD -1.9 cm, 95% CI -2.4 to-1.4), perianal surgery (AMHD -1.5 cm, 95% CI -2.3 to -0.7), or inpatient treatment for >30 days listing IBD as the primary diagnosis (AMHD -1.4 cm, 95% CI -1.8 to -1.0) during childhood. Patients with IBD had an increased risk of growth retardation compared to general population reference individuals (OR 1.99, 95% CI 1.68 to 2.37). In study 3, we analysed the positive predictive value (PPV) of the commonly used register-based algorithm (≥2 diagnostic listings) for childhood-onset IBD in the NPR and its subtypes, both for prevalent and incident definitions. We also studied the PPV of childhood-onset IBD diagnosis using Swibreg and combining IBD listings in the NPR and pathology codes from the ESPRESSO cohort. We found the PPV of a commonly used register-based definition of childhood-onset IBD in the NPR (at least two diagnostic listings of IBD) to be high (PPV=93%) when using the Copenhagen criteria based on medical chart review as the gold standard. The PPV for a definition also using pathology reports suggestive of IBD was even higher (97%) and 100% for patients registered in SWIBREG. Using the revised Porto criteria as the gold standard, the PPV for different IBD subtypes based on ICD codes in the NPR at the start of follow-up (incident definition) was 78% for CD and 74% for UC and somewhat higher at the end of follow-up (prevalent definition: 88% for CD and 71% for UC). In study 4, we identified 5308 patients with childhood-onset IBD in the NPR and ESPRESSO cohorts from 2006 until 2020 using ICD codes or a combination of ICD codes with pathology codes and further stratified them by age of IBD onset [infantile onset (<2 years), preschool onset (2-<6), very early onset (<6, VEO-IBD), early onset IBD (6-<10) and adolescent onset (10-<18)]. We described the incidence of VEO-IBD patients (<6 years of age) and analysed and compared health care use (medications, hospitalisations, outpatient visits, surgeries) in VEO-IBD patients compared to older groups. We analysed all these outcomes separately in infantile and toddler groups. The incidences of all childhood-onset IBD age groups (including VEO-IBD) were stable. VEOIBD patients were equally exposed to steroids but significantly less exposed to 5ASA, immunomodulators and targeted therapies (mostly driven by the infantile-onset group) than older-onset children. Time to first hospitalization was shorter in the infantile group while yearly rate of hospitalizations after the second year and of outpatient visits after the year of diagnosis was similar across age groups. The number of surgeries were low and there were no significant differences between VEO-IBD and older onset IBD patients

Identification of Childhood-Onset Inflammatory Bowel Disease in Swedish Healthcare Registers : A Validation Study

Purpose: The Swedish National Patient Register (NPR) is often used in observational studies of childhood-onset inflammatory bowel disease (IBD) (&lt;18 years of age) and its subtypes, but the validity of previously used register-based algorithms for capturing childhood-onset IBD has never been examined. Methods: We identified a random sample of 233 individuals with at least two first ever diagnostic listings of IBD in the NPR between 2002 and 2014. We calculated the test characteristics for different register-based definitions of IBD and its subtypes using the Copenhagen criteria and the revised Porto criteria as gold standard, both based on medical chart review. We made assumptions of the occurrence of undiagnosed IBD in the general child population based on available literature. Results: Out of 233 individuals with at least two diagnostic listings of IBD, 216 had true IBD, resulting in a positive predictive value (PPV) = 93% (95% confidence interval (CI) 89–96), sensitivity = 88% (95% CI 83–92), specificity = 100% (95% CI 100–100), and negative predictive value (NPV) = 100% (95% CI 100–100). The PPV for the NPR-based definitions of IBD subtypes at time of first IBD diagnosis and at end of follow-up were 78% (95% CI 69–86) and 88% (95% CI 80–94), respectively, for Crohn’s disease and 74% (95% CI 63–83) and 71% (95% CI 60–80), respectively, for ulcerative colitis. Conclusion: The validity of register-based definitions of childhood-onset IBD in the Swedish NPR is high and can be used to identify patients in observational research

Associations between food and beverage consumption and different types of sedentary behaviours in European preschoolers: the ToyBox-study

OBJECTIVE: To examine the association between food and beverage consumption and time spent in different sedentary behaviours such as watching TV and DVDs, playing computer/video games and quiet play/activities in preschoolers. METHODS: A sample of 6431 (51.8 % males) European preschoolers aged 3.5-5.5 years from six survey centres was included in the data analyses. Data on dietary habits and sedentary behaviours [watching TV, playing computer and quiet play (both during weekdays and weekend days)] were collected via standardized proxy-administered questionnaires. One-way analysis of covariance and general linear model (adjusted for sex, maternal education, body mass index and centre) were conducted. RESULTS: The results of the generalized linear model showed that the more strong associations in both males and females who were watching TV for > 1 h/day during weekdays were positively associated with increased consumption of fizzy drinks (β = 0.136 for males and β = 0.156 for females), fresh and packed juices (β = 0.069, β = 0.089), sweetened milk (β = 0.119, β = 0.078), cakes and biscuits (β = 0.116, β = 0.145), chocolate (β = 0.052, β = 0.090), sugar-based desserts and pastries (β = 0.234, β = 0.250), salty snacks (β = 0.067, β = 0.056), meat/poultry/processed meat (β = 0.067, β = 0.090) and potatoes (β = 0.071, β = 0.067), and negative associations were observed for the consumption of fruits (β = -0.057, β = -0.099), vegetables (β = -0.056, β = -0.082) and fish (β = -0.013, β = -0.013). During weekend days, results were comparable. CONCLUSIONS: In European preschoolers, sedentary behaviours were associated with consumption of energy-dense foods and fizzy drinks. The present findings will contribute to improve the strategies to prevent overweight, obesity and nutrition-related chronic diseases from early childhood

Safety and Potential Efficacy of Escalating Dose of Ustekinumab in Pediatric Crohn Disease (the Speed-up Study) : A Multicenter Study from the Pediatric IBD Porto Group of ESPGHAN

Objectives: Escalation of the ustekinumab (UST) maintenance dosage was effective in adults with Crohn disease (CD), but no data are available for children. We evaluated the effectiveness and safety of dose escalation of UST in pediatric CD.Methods: This was a retrospective multicenter study from 25 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. We included children with CD who initiated UST at a standard dosing and underwent either dose escalation to intervals shorter than 8 weeks or re-induction of UST due to active disease. Demographic. clinical, laboratory, endoscopic. imaging, and safety data were collected up to 12 months of follow-up.Results: Sixty-nine children were included (median age 15.8 years, interquartile range 13.8-16.9) with median disease duration of 4.3 years (2.9-6.3). Most children were biologic (98.6%)- and immunomodulator (86.8%)- experienced. Clinical response and remission were observed at 3 months after us r escalation in 46 (67%) and 29 (42%) children. respectively. The strongest predictor for clinical remission was lower weighted Pediatric Crohn Disease Activity Index (wPCDAI) at escalation (P= 0.001). The median C-reactive protein level decreased from 14 (3-28.03) to 5 (1.1 -20.5) mg/L (P = 0.012), and the fecal calprotectin level from 1100 (500-2300) to 515 (250-1469) mu g/g (P= 0.012) 3 months post-escalation. Endoscopic and transmural healing were achieved in 3 of 19 (16%) and 2 of 15 (13%) patients, respectively. Thirteen patients (18.8%) discontinued therapy due to active disease. No serious adverse events were reported.Conclusions: Two-thirds of children with active CD responded to dose escalation of UST. Milder disease activity may predict a favorable outcome following UST dose escalation.Peer reviewe

Safety and Potential Efficacy of Escalating Dose of Ustekinumab in Pediatric Crohn Disease (the Speed-up Study): A Multicenter Study from the Pediatric IBD Porto Group of ESPGHAN

OBJECTIVES: Escalation of the ustekinumab (UST) maintenance dosage was effective in adults with Crohn disease (CD), but no data are available for children. We evaluated the effectiveness and safety of dose escalation of UST in pediatric CD. METHODS: This was a retrospective multicenter study from 25 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. We included children with CD who initiated UST at a standard dosing and underwent either dose escalation to intervals shorter than 8 weeks or re-induction of UST due to active disease. Demographic, clinical, laboratory, endoscopic, imaging, and safety data were collected up to 12 months of follow-up. RESULTS: Sixty-nine children were included (median age 15.8 years, interquartile range 13.8-16.9) with median disease duration of 4.3 years (2.9-6.3). Most children were biologic (98.6%)- and immunomodulator (86.8%)- experienced. Clinical response and remission were observed at 3 months after UST escalation in 46 (67%) and 29 (42%) children, respectively. The strongest predictor for clinical remission was lower weighted Pediatric Crohn Disease Activity Index (wPCDAI) at escalation ( P = 0.001). The median C-reactive protein level decreased from 14 (3-28.03) to 5 (1.1-20.5) mg/L ( P = 0.012), and the fecal calprotectin level from 1100 (500-2300) to 515 (250-1469) µg/g ( P = 0.012) 3 months post-escalation. Endoscopic and transmural healing were achieved in 3 of 19 (16%) and 2 of 15 (13%) patients, respectively. Thirteen patients (18.8%) discontinued therapy due to active disease. No serious adverse events were reported. CONCLUSIONS: Two-thirds of children with active CD responded to dose escalation of UST. Milder disease activity may predict a favorable outcome following UST dose escalation

Intestinal stroma guides monocyte differentiation to macrophages through GM-CSF

Abstract Stromal cells support epithelial cell and immune cell homeostasis and play an important role in inflammatory bowel disease (IBD) pathogenesis. Here, we quantify the stromal response to inflammation in pediatric IBD and reveal subset-specific inflammatory responses across colon segments and intestinal layers. Using data from a murine dynamic gut injury model and human ex vivo transcriptomic, protein and spatial analyses, we report that PDGFRA+CD142− /low fibroblasts and monocytes/macrophages co-localize in the intestine. In primary human fibroblast-monocyte co-cultures, intestinal PDGFRA+CD142− /low fibroblasts foster monocyte transition to CCR2+CD206+ macrophages through granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocyte-derived CCR2+CD206+ cells from co-cultures have a phenotype similar to intestinal CCR2+CD206+ macrophages from newly diagnosed pediatric IBD patients, with high levels of PD-L1 and low levels of GM-CSF receptor. The study describes subset-specific changes in stromal responses to inflammation and suggests that the intestinal stroma guides intestinal macrophage differentiation

Associations between food and beverage consumption and different types of sedentary behaviours in European preschoolers: the ToyBox-study

© 2016, Springer-Verlag Berlin Heidelberg. Objective: To examine the association between food and beverage consumption and time spent in different sedentary behaviours such as watching TV and DVDs, playing computer/video games and quiet play/activities in preschoolers. Methods: A sample of 6431 (51.8 % males) European preschoolers aged 3.5–5.5 years from six survey centres was included in the data analyses. Data on dietary habits and sedentary behaviours [watching TV, playing computer and quiet play (both during weekdays and weekend days)] were collected via standardized proxy-administered questionnaires. One-way analysis of covariance and general linear model (adjusted for sex, maternal education, body mass index and centre) were conducted. Results: The results of the generalized linear model showed that the more strong associations in both males and females who were watching TV for > 1 h/day during weekdays were positively associated with increased consumption of fizzy drinks (β = 0.136 for males and β = 0.156 for females), fresh and packed juices (β = 0.069, β = 0.089), sweetened milk (β = 0.119, β = 0.078), cakes and biscuits (β = 0.116, β = 0.145), chocolate (β = 0.052, β = 0.090), sugar-based desserts and pastries (β = 0.234, β = 0.250), salty snacks (β = 0.067, β = 0.056), meat/poultry/processed meat (β = 0.067, β = 0.090) and potatoes (β = 0.071, β = 0.067), and negative associations were observed for the consumption of fruits (β = −0.057, β = −0.099), vegetables (β = −0.056, β = −0.082) and fish (β = −0.013, β = −0.013). During weekend days, results were comparable. Conclusions: In European preschoolers, sedentary behaviours were associated with consumption of energy-dense foods and fizzy drinks. The present findings will contribute to improve the strategies to prevent overweight, obesity and nutrition-related chronic diseases from early childhood

Dietary patterns and their relationship with the perceptions of healthy eating in European adolescents : the HELENA study

Objective: The aim of this study was to identify dietary patterns (DPs) in European adolescents and to examine the association between perceptions of healthy eating and the obtained DPs. Method: A multinational cross-sectional study was carried out in adolescents aged 12.5 to 17.5?years and 2,027 (44.9% males) were considered for analysis. A self-reported questionnaire with information on food choices and preferences, including perceptions of healthy eating, and two 24-hour dietary recalls were used. Principal component analysis was used to obtain sex-specific DPs, and linear analyses of covariance were used to compare DPs according to perceptions of healthy eating. Results: Three and four DPs for boys and girls were obtained. In boys and girls, there were significant associations between some perceptions about healthy food and the Breakfast-DP (p?<?0.05). In boys, Breakfast-DP and Healthy Beverage-DP were associated with the perception of the own diet as healthy (p?<?0.05). Healthy Beverage-DP was associated with those disliking fruits and vegetables (p?<?0.05). Girls considering the own diet as healthy were associated with Mediterranean-DP, Breakfast-DP, and Unhealthy Beverage and Meat-DP (p?<?0.05). The perception of snacking as a necessary part of a healthy diet was associated with Breakfast-DP in both genders (p?<?0.05). Conclusions: In European adolescents, perceptions of healthy eating were mainly associated with a DP characterized by foods consumed at breakfast. Future studies should further explore these findings in order to implement health promotion programs to improve healthy eating habits in adolescents