Publications by authors named "M M Tabbers"

106 Publications

Bowel Lengthening Procedures in Children with Short Bowel Syndrome: A Systematic Review.

Eur J Pediatr Surg 2021 Mar 4. Epub 2021 Mar 4.

Pediatric Surgical Centre, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands.

Introduction:  The aims of the study are to systematically assess and critically appraise the evidence concerning two surgical techniques to lengthen the bowel in children with short bowel syndrome (SBS), namely, the longitudinal intestinal lengthening and tailoring (LILT) and serial transverse enteroplasty (STEP), and to identify patient characteristics associated with a favorable outcome.

Materials And Methods:  MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception till December 2019. No language restriction was used.

Results:  In all, 2,390 articles were found, of which 40 were included, discussing 782 patients. The median age of the patients at the primary bowel lengthening procedure was 16 months (range: 1-84 months). Meta-analysis could not be performed due to the incomparability of the groups, due to heterogeneous definitions and outcome reporting. After STEP, 46% of patients weaned off parenteral nutrition (PN) versus 52% after LILT. Mortality was 7% for STEP and 26% for LILT. Patient characteristics predictive for success (weaning or survival) were discussed in nine studies showing differing results. Quality of reporting was considered poor to fair.

Conclusion:  LILT and STEP are both valuable treatment strategies used in the management of pediatric SBS. However, currently it is not possible to advise surgeons on accurate patient selection and to predict the result of either intervention. Homogenous, prospective, outcome reporting is necessary, for which an international network is needed.
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http://dx.doi.org/10.1055/s-0041-1725187DOI Listing
March 2021

Antidepressants for functional abdominal pain disorders in children and adolescents.

Cochrane Database Syst Rev 2021 02 9;2:CD008013. Epub 2021 Feb 9.

Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.

Background: Functional Abdominal Pain Disorders (FAPDs) present a considerable burden to paediatric patients, impacting quality of life, school attendance and causing higher rates of anxiety and depression disorders. There are no international guidelines for the management of this condition. A previous Cochrane Review in 2011 found no evidence to support the use of antidepressants in this context.

Objectives: To evaluate the current evidence for the efficacy and safety of antidepressants for FAPDs in children and adolescents.

Search Methods: In this updated review, we searched the Cochrane Library, PubMed, MEDLINE, Embase, PsycINFO and two clinical trial registers from inception until 03 February 2020. We also updated our search of databases of ongoing research, reference lists and 'grey literature' from inception to 03 February 2020.

Selection Criteria: We included randomised controlled trials (RCTs) comparing antidepressants to placebo, to no treatment or to any other intervention, in children aged 4 to 18 years with a FAPD diagnosis as per the Rome or any other defined criteria (as defined by the authors). The primary outcomes of interest included treatment success (as defined by the authors), pain severity, pain frequency and withdrawal due to adverse events.

Data Collection And Analysis: Two review authors checked all citations independently, resolving disagreement with a third-party arbiter. We reviewed all potential studies in full text, and once again made independent decisions, with disagreements resolved by consensus. We conducted data extraction and 'Risk of bias' assessments independently, following Cochrane methods. Where homogeneous data were available, we performed meta-analysis using a random-effects model. We conducted GRADE analysis.

Main Results: We found one new study in this updated search, making a total of three trials (223 participants) eligible for inclusion: two using amitriptyline (AMI) and one using citalopram. For the primary outcome of treatment success, two studies used reports of success on a symptom-based Likert scale, with either a two-point reduction or the two lowest levels defined as success. The third study defined success as a 15% improvement in quality of life (QOL) ratings scales. Therefore, meta-analysis did not include this final study due to the heterogeneity of the outcome measure. There is low-certainty evidence that there may be no difference when antidepressants are compared with placebo (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.87 to 1.56; 2 studies, 205 participants; I = 0%). We downgraded the evidence for significant imprecision due to extremely sparse data (see Summary of findings table 1). The third study reported that participants receiving antidepressants were significantly more likely than those receiving placebo to experience at least a 15% improvement in overall QOL score at 10 and 13 weeks (P = 0.007 and P = 0.002, respectively (absolute figures were not given)). The analysis found no difference in withdrawals due to adverse events between antidepressants and placebo: RR 3.17 (95% CI 0.65 to 15.33), with very low certainty due to high risk of bias in studies and imprecision due to low event and participant numbers. Sensitivity analysis using a fixed-effect model and analysing just for AMI found no change in this result. Due to heterogeneous and limited reporting, no further meta-analysis was possible.

Authors' Conclusions: There may be no difference between antidepressants and placebo for treatment success of FAPDs in childhood. There may be no difference in withdrawals due to adverse events, but this is also of low certainty. There is currently no evidence to support clinical decision making regarding the use of these medications. Further studies must consider sample size, homogenous and relevant outcome measures and longer follow up.
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http://dx.doi.org/10.1002/14651858.CD008013.pub3DOI Listing
February 2021

Congenital Diarrhea and Cholestatic Liver Disease: Phenotypic Spectrum Associated with MYO5B Mutations.

J Clin Med 2021 01 28;10(3). Epub 2021 Jan 28.

Department of Pediatrics I, Medical University of Innsbruck, A-6020 Innsbruck, Austria.

Myosin Vb (MYO5B) is a motor protein that facilitates protein trafficking and recycling in polarized cells by RAB11- and RAB8-dependent mechanisms. Biallelic MYO5B mutations are identified in the majority of patients with microvillus inclusion disease (MVID). MVID is an intractable diarrhea of infantile onset with characteristic histopathologic findings that requires life-long parenteral nutrition or intestinal transplantation. A large number of such patients eventually develop cholestatic liver disease. Bi-allelic MYO5B mutations are also identified in a subset of patients with predominant early-onset cholestatic liver disease. We present here the compilation of 114 patients with disease-causing MYO5B genotypes, including 44 novel patients as well as 35 novel MYO5B mutations, and an analysis of MYO5B mutations with regard to functional consequences. Our data support the concept that (1) a complete lack of MYO5B protein or early MYO5B truncation causes predominant intestinal disease (MYO5B-MVID), (2) the expression of full-length mutant MYO5B proteins with residual function causes predominant cholestatic liver disease (MYO5B-PFIC), and (3) the expression of mutant MYO5B proteins without residual function causes both intestinal and hepatic disease (MYO5B-MIXED). Genotype-phenotype data are deposited in the existing open MYO5B database in order to improve disease diagnosis, prognosis, and genetic counseling.
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http://dx.doi.org/10.3390/jcm10030481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865828PMC
January 2021

Evaluation of the "3 Good Questions" program for shared decision-making in pediatric medicine: a feasibility study.

Eur J Pediatr 2021 Apr 9;180(4):1235-1242. Epub 2020 Nov 9.

Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology, Room C2-312, PO Box 22700, 1100, DD, Amsterdam, The Netherlands.

The "3 Good Questions" program was developed to increase shared decision making. The current pilot-study determined the feasibility of these questions to increase shared decision-making in Dutch pediatric medicine. Pre-/postintervention surveys were used to include children (10-18 years) at pediatric outpatient clinics of four hospitals in the Netherlands. After their appointment, two different groups of children completed the questionnaires. Group 1 filled in the survey before the intervention; group 2 completed the survey after active implementation of the "3 Good Questions" program. The primary outcome was to determine the feasibility (reach, applicability). Secondary outcomes were related to patient involvement in healthcare and treatment decisions and decision-making process between child and healthcare professional. In total, 168 and 114 children in groups 1 and 2 (61 vs 63% female, P = 0.68; age 13.3 ± 2.4 vs 13.8 ± 2.4 years, P = 0.72), respectively, completed the questionnaire. In group 2, 44% of children were aware of the "3 Good Questions", of whom 18% posed ≥ 1 of the "3 Good Questions" during their appointment (feasibility). The "3 Good Questions" program led to more shared decision-making (SDM-Q-9: P = < 0.001;95%CI: - 2.43 to - 1.17). The majority of children who have read or heard of the "3 Good Questions" would recommend this program to other children.Conclusion: Implementation of the "3 Good Questions" program seemed feasible, although it is necessary to further explore the implementation of this program at national level as a simple way for children and healthcare professionals to share decisions in practice. What is known • Children have the right to be included in decision-making, and inclusion can improve patient satisfaction and quality of care, and reduce costs. • The "3 Good Questions" program was successfully implemented in adult healthcare to increase shared decision making, and therefore these "3 Good Questions" have been adapted to a child version. What is new • In this pilot study, we found that the implementation of the "3 Good Questions" program to increase shared decision-making in pediatric medicine seemed feasible. Although it is necessary to further explore the implementation of the "3 Good Questions" program at national level as a simple way for children and healthcare professionals to share decisions in practice.
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http://dx.doi.org/10.1007/s00431-020-03868-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940148PMC
April 2021

The prevalence of liver fibrosis according to non-invasive tools in a pediatric home parenteral nutrition cohort.

Clin Nutr 2021 Feb 11;40(2):460-466. Epub 2020 Jun 11.

Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, the Netherlands.

Background & Aims: Liver biopsy is no viable tool to routinely screen for liver fibrosis in children suffering from chronic intestinal failure (IF). We aim to assess the prevalence of liver fibrosis in a cohort of children with chronic IF by non-invasive tests: transient elastography (TE), aspartate-aminotransferase-to-platelet-ratio-index (APRI) and enhanced liver fibrosis (ELF) score.

Methods: Cross sectional study where patients with chronic IF, receiving parenteral nutrition (PN) for at least 3 months, were enrolled. TE, APRI and ELF score were measured. Using Spearman's rank correlation coefficient and Kruskal-Wallis H test, the correlation between TE, APRI, ELF score and known risk factors for development of intestinal failure-associated liver disease (IFALD) were calculated.

Results: 32 patients were included (50% female), median age was 8 years and 4 months, median PN duration was 45 months. Six patients (21%) had TE ≥6.5 kPa, indicating significant fibrosis. Twelve patients (38%) had APRI ≥.5, indicating fibrosis. ELF score indicated moderate fibrosis in 17 patients (63%) and significant fibrosis in 10 patients (37%). TE and APRI correlated significantly with known risk factors for IFALD, but ELF showed poor correlation with known risk factors for IFALD.

Conclusion: In a cohort of pediatric patients suffering from chronic IF, TE measurement, APRI and ELF test show a varying, but substantial proportion of subjects with fibrosis. The diagnostic value of these tests and their role in the management of pediatric IF must be determined in larger cohorts with liver biopsy as reference standard.

Trial Registration: Academic Medical Center medical ethics committee number: METC 2017_185.
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http://dx.doi.org/10.1016/j.clnu.2020.05.039DOI Listing
February 2021

Prevalence of Functional Gastrointestinal Disorders in European Infants and Toddlers.

J Pediatr 2020 06;221:107-114

Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, The Netherlands.

Objective: To assess the prevalence of functional gastrointestinal disorders (FGIDs) in young children in a cross-sectional, multicenter study in Belgium, Italy, and The Netherlands.

Study Design: Children were enrolled if they were age 0-48 months, attending a general pediatrician (Belgium, Italy) or a well-baby clinic (The Netherlands) for routine follow-up. Separate questionnaires were developed for infants age 0-12 months and for toddlers age 13-48 months. Questionnaires evaluated the clinical history, symptoms, sociodemographic information on the family, and exposure to stressful life events. FGIDs were defined according to Rome IV criteria.

Results: In total 2751 children were included: 1698 infants age 0-12 months and 1053 children age 13-48 months. The prevalence of any FGID in infants age 0-12 months and 13-48 months was 24.7% and 11.3%, respectively. The most common disorders were infant regurgitation (13.8%) in infants and functional constipation (9.6%) in toddlers. Multivariable regression analyses demonstrated that younger age (P = .030) and formula feeding (P = .045) were associated with the prevalence of any FGID among infants. Country (Italy) (P = .033) and parents subjected to domestic violence (P = .035) were associated with the prevalence of any FGID in toddlers age 13-48 months.

Conclusions: FGIDs are common in a community sample of Western European infants and toddlers. Regurgitation is most prevalent in infants and functional constipation is most common in toddlers. Younger age, formula feeding, and domestic violence to parents are associated with the prevalence of FGIDs.
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http://dx.doi.org/10.1016/j.jpeds.2020.02.076DOI Listing
June 2020

A Core Outcome Set for Clinical Trials in Pediatric Functional Abdominal Pain Disorders.

J Pediatr 2020 06 17;221:115-122.e5. Epub 2020 Apr 17.

Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, The Netherlands.

Objective: To ensure consistency and reduce outcome measure reporting heterogeneity in clinical trials on pediatric functional abdominal pain disorders (FAPDs), a core outcome set (COS) was developed for pediatric FAPD trials.

Study Design: A mixed-method 2-round Delphi technique was used and key stakeholders, including healthcare professionals (HCPs), patients with FAPD, and their parents were invited to participate. In the first round, key stakeholders identified outcomes of importance through an open-ended questionnaire. Outcomes mentioned by ≥10% of the participants were included in a shortlist. In the second round, this shortlist was rated and prioritized. During a consensus meeting with an expert panel, the final COS was defined.

Results: The first round was completed by 152 of 210 (72%) HCPs, 103 (100%) parents, and 50 of 54 (93%) patients. A total of 104 from 167 (62%) HCPs, 102 (100%) parents, and 53 (100%) patients completed round 2. Pain intensity, pain frequency, quality of life, school attendance, anxiety/depression, adequate relief, defecation pattern (disease specific, irritable bowel syndrome), and adverse events were included in the final COS for FAPDs.

Conclusion: A set of 8 core outcomes has been identified that should minimally be measured in pediatric FAPD trials. Implementation of the use of this COS will increase comparison between studies and, therefore, improve management of children with FAPDs.
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http://dx.doi.org/10.1016/j.jpeds.2020.02.032DOI Listing
June 2020

Do Antibiotics Reduce the Incidence of Infections After Percutaneous Endoscopic Gastrostomy Placement in Children?

J Pediatr Gastroenterol Nutr 2020 07;71(1):23-28

Pediatric Gastroenterology.

Objective: Percutaneous endoscopic gastrostomy (PEG) provides a long-term solution for tube dependency. Pediatric guidelines recommend prophylactic antibiotic treatment (ABT) based on adult studies.

Aim: To compare wound infection and other complications in children receiving a PEG with and without prophylactic ABT.

Methods: Retrospective study including children 0 to 18 years undergoing PEG placement. Patients with (2010-2013) and without (2000-2010) ABT were compared with respect to the occurrence of wound infection and other complications.

Results: In total, 297 patients were included (median age 2.9 years, 53% boys). Patients receiving ABT per PEG protocol (n = 78) had a similar wound infection rate (17.9% vs 21%, P = 0.625), significantly less fever (3.8% vs 14.6%, P = 0.013), leakage (0% vs 9.1%, P = 0.003) and shorter hospital admission (2 vs 4 days, P = 0.000), but more overgranulation (28.2% vs 8.7%, P = 0.000) compared with those without (n = 219). Patients receiving any ABT, per PEG protocol or clinical indication (n = 115), had similar occurrence of wound infection (19.1% vs 20.9%, P = 0.768), fever (7.8% vs 14.3%, P = 0.100) and leakage (3.5% vs 8.8%, P = 0.096), a significantly shorter hospital admission (3 vs 4 days, P = 0.000), but more overgranulation (21.7% vs 8.8%, P =0.003) compared with those without (n = 182).

Conclusions: Prophylactic ABT does not seem to reduce the occurrence of wound infection but it might be beneficial with respect to fever, leakage and duration of hospital admission, but not overgranulation. A randomized controlled trial is needed to confirm our results.
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http://dx.doi.org/10.1097/MPG.0000000000002709DOI Listing
July 2020

Standardized and Individualized Parenteral Nutrition Mixtures in a Pediatric Home Parenteral Nutrition Population.

J Pediatr Gastroenterol Nutr 2020 02;70(2):269-274

Department of Pediatric Gastroenterology, Hepatology and Nutrition, Emma Children's Hospital, University of Amsterdam, Amsterdam UMC, Amsterdam.

Objectives: Studies evaluating efficacy or safety of standardized parenteral nutrition (PN) versus individualized PN are lacking. We aimed to assess effects on growth and safety of standardized PN compared with individualized PN in our Home PN group.

Methods: Descriptive cohort study in Dutch children on Home PN, in which standardized PN was compared with individualized PN. Both groups received similar micronutrient-supplementation. Primary outcome was growth over 2 years, secondary outcomes were electrolyte disturbances and biochemical abnormalities. Additionally, patients were matched for age to control for potential confounding characteristics.

Results: Fifty patients (50% girls, median age 6.5 years) were included, 16 (32%) received standardized PN mixtures. Age (11 vs 5 years), gestational age (39.2 vs 36.2 weeks) and PN duration (97 vs 39 months) were significantly higher in the group receiving standardized PN (P: ≤0.001; 0.027; 0.013 respectively). The standardized PN group showed an increase in weight-for-age (WFA), compared with a decrease in the individualized PN group (+0.38 SD vs -0.55 SD, P: 0.003). Electrolyte disturbances and biochemical abnormalities did not differ. After matching for age, resulting in comparable groups, no significant differences were demonstrated in WFA, height-for-age, or weight-for-height SD change.

Conclusions: In children with chronic IF, over 2,5 years of age, standardized PN mixtures show a comparable effect on weight, height, and weight for height when compared with individualized PN mixtures. Also, standardized PN mixtures (with added micronutrients) seem noninferior to individualized PN mixtures in terms of electrolyte disturbances and basic biochemical abnormalities. Larger studies are needed to confirm these conclusions.

Trial Registration: Academical Medical Center medical ethics committee number W18_079 #18.103.
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http://dx.doi.org/10.1097/MPG.0000000000002528DOI Listing
February 2020

The Role of a Nutrition Support Team in the Management of Intestinal Failure Patients.

Nutrients 2020 Jan 8;12(1). Epub 2020 Jan 8.

Amsterdam UMC, Department of Pediatric Gastroenterology, University of Amsterdam, Emma Children's Hospital, Hepatology and Nutrition, 1105 AZ Amsterdam, The Netherlands.

Parenteral nutrition (PN) is a complex and specialized form of nutrition support that has revolutionized the care for both pediatric and adult patients with acute and chronic intestinal failure (IF). This has led to the development of multidisciplinary teams focused on the management of patients receiving PN: nutrition support teams (NSTs). In this review we aim to discuss the historical aspects of IF management and NST development, and the practice, composition, and effectiveness of multidisciplinary care by NSTs in patients with IF. We also discuss the experience of two IF centers as an example of contemporary NSTs at work. An NST usually consists of at least a physician, nurse, dietitian, and pharmacist. Multidisciplinary care by an NST leads to fewer complications including infection and electrolyte disturbances, and better survival for patients receiving short- and long-term PN. Furthermore, it leads to a decrease in inappropriate prescriptions of short-term PN leading to significant cost reduction. Complex care for patients receiving PN necessitates close collaboration between team members and NSTs from other centers to optimize safety and effectiveness of PN use.
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http://dx.doi.org/10.3390/nu12010172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019598PMC
January 2020

Bowel ultrasound measurements in healthy children - systematic review and meta-analysis.

Pediatr Radiol 2020 04 14;50(4):501-508. Epub 2019 Dec 14.

Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Background: Ultrasound (US) is a noninvasive method of assessing the bowel that can be used to screen for bowel pathology, such as Inflammatory Bowel Disease, in children. Knowledge about US findings of the bowel in healthy children is important for interpreting US results in cases where disease is suspected.

Objective: To assess the bowel wall thickness in different bowel segments in healthy children and to assess differences in bowel wall thickness among pediatric age categories.

Materials And Methods: We conducted a systematic search in the PubMed, Embase, Cochrane, and CINAHL databases for studies describing bowel wall thickness measured by transabdominal US in healthy children. We excluded studies using contrast agent. We calculated the pooled mean and standard deviation scores and assessed differences among age categories (0-4 years, 5-9 years, 10-14 years, 15-18 years), first with analysis of variance (ANOVA) and further with subsequent Student's t-tests for independent samples, corrected for multiple testing.

Results: We identified 191 studies and included 7 of these studies in the systematic review. Reported bowel wall thickness values ranged from 0.8 mm to 1.9 mm in the small bowel and from 1.0 mm to 1.9 mm in the colon. The mean colonic bowel wall thickness is larger in children ages 15-19 years compared to 0-4 years (range in difference: 0.3-0.5 mm [corrected P<0.02]).

Conclusion: The reported upper limit of bowel wall thickness in healthy children is 1.9 mm in the small bowel and the colon, and mean thickness increases slightly with age in jejunum and colon. These values can be used as guidance when screening for bowel-related pathology in children.
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http://dx.doi.org/10.1007/s00247-019-04567-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067709PMC
April 2020

[Foreign body ingestion in children].

Ned Tijdschr Geneeskd 2019 11 7;163. Epub 2019 Nov 7.

Emma Kinderziekenhuis, Amsterdam UMC, locatie AMC-UvA, Afd. Kinder-mdl, Amsterdam.

Foreign body ingestion occurs frequently in children and may lead to severe complications and mortality. In this article, three cases are presented. A 2-year-old boy swallowed a plastic toy helmet. He had no symptoms and physical examination was normal, and the toy was found in the stool within three days. Similarly, a 6-year-old girl swallowed two magnets and was asymptomatic. Physical examination was normal and a radiograph showed a foreign body which had passed the stomach. Due to the location, endoscopic removal by gastroduodenoscopy was not possible and surgical removal unnecessary. The magnets were secreted in the stool within two days. A 10-year-old boy with VACTERL association and psychiatric history, swallowed a button battery. After a delay in presentation, a radiograph showed a button battery mid-esophageal, which was endoscopically removed. He also needed dilatation due to esophageal stenosis. The above cases are all illustrative of the topic covered in the guideline 'Ingestion of foreign bodies in children aged 0-18 years', which was developed on behalf of the Dutch Pediatric Association and published in March 2019.
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November 2019

Physiotherapy for Children with Functional Constipation: A Pragmatic Randomized Controlled Trial in Primary Care.

J Pediatr 2020 01 12;216:25-31.e2. Epub 2019 Nov 12.

Department of General Practice and Elderly Care Medicine, University of Groningen, University Medical Center, Groningen, the Netherlands.

Objective: To determine the effectiveness of physiotherapy plus conventional treatment compared with conventional treatment alone for the treatment of functional constipation in children age 4-17 years in primary care.

Study Design: Pragmatic randomized controlled trial with 8 months follow-up. Primary care physicians recruited children diagnosed with functional constipation (n = 234), and pediatricians recruited newly referred children with a diagnosis of functional constipation (n = 11). Conventional treatment comprised toilet training, nutritional advice, and laxative prescribing, whereas physiotherapy focused on resolving dyssynergic defecation. The primary outcome was treatment success over 8 months, defined as the absence of functional constipation (Rome III criteria) without laxative use. Secondary outcomes included the absence of functional constipation irrespective of continuation of laxative use and global perceived treatment effect.

Results: Children were allocated to conventional treatment plus physiotherapy or conventional treatment alone (67 per group), mean (SD) age was 7.6 (3.5) years. Results of longitudinal analyses in the intention-to-treat population showed that the treatment success percentage was not statistically improved by adding physiotherapy to conventional treatment (adjusted relative risk [aRR] 0.80, 95% CI 0.44-1.30). At 4 months, fewer children receiving physiotherapy had treatment success (17%) than children receiving conventional treatment alone (28%), but this had equalized by 8 months (42% and 41%, respectively). The percentage of children without functional constipation, irrespective of continuation of laxative use, was not statistically different between groups over 8 months (aRR 1.12, 95% CI 0.82-1.34). Notably, parents reported significantly more global symptom improvement after physiotherapy than after conventional treatment (aRR 1.40; 95% CI 1.00-1.73).

Conclusions: We find no evidence to recommend physiotherapy for all children with functional constipation in primary care.

Trial Registration: Netherlands Trial Registry: NTR4797.
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http://dx.doi.org/10.1016/j.jpeds.2019.09.048DOI Listing
January 2020

[Guideline 'Ingestion of foreign bodies in children aged 0-18 years'].

Ned Tijdschr Geneeskd 2019 11 7;163. Epub 2019 Nov 7.

Emma Kinderziekenhuis, Amsterdam UMC, locatie AMC-UvA, afd. Kinder-mdl, Amsterdam.

The guideline 'Ingestion of foreign bodies in children aged 0-18 years' was developed by a multidisciplinary working group on behalf of the Dutch Pediatric Association and published in March 2019. The ingestion of foreign bodies can lead to severe complications and even mortality The absence of symptoms does not rule out the ingestion of a foreign body. In the secondary and tertiary care setting, radiographs should be performed in both symptomatic and asymptomatic children with a suspicion of foreign body ingestion. It is essential to visualize from the teeth down to the abdomen on the anterior-posterior and, possible lateral, radiograph. The timing of endoscopic removal depends on type and localization of the foreign body and symptoms of the child.
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November 2019

Reporting on outcome measures in pediatric chronic intestinal failure: A systematic review.

Clin Nutr 2020 Jul 10;39(7):1992-2000. Epub 2019 Sep 10.

Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, the Netherlands.

Background & Aims: Chronic intestinal failure (IF) in children is a rare and heterogeneous disease requiring treatment with parenteral nutrition. A uniform definition for chronic IF and standardized outcome measures to compare therapeutic trials in these children are lacking. Therefore, the aim of this study is to systematically assess how definitions and outcome measures are defined in therapeutic trials of children with chronic IF.

Methods: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception till August 2018. No language restriction was used.

Results: A total of 1766 articles was found of which 70 studies fulfilled our inclusion criteria. 54 studies (76%) did not report any definition of IF. Of the 16 studies (23%) which reported a definition of IF, 7 different definitions were found. The two most frequently used definitions were: (1) the inability to absorb adequate nutrients to maintain body weight or normal growth and development (n = 5), and (2) the dependence upon parenteral nutrition to maintain minimal energy requirements for growth and development (n = 5). A total of 117 different outcomes were reported. The three most reported outcome measures were: mortality (n = 27), liver enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl trans peptidase) (n = 27), and growth (n = 23). Quality of reporting was considered fair to poor in most studies.

Conclusion: There is a lack of reported definitions in studies concerning pediatric IF. Heterogeneity exists in outcome reporting in research concerning pediatric chronic IF. Therefore, we recommend the development of a core outcome set.
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http://dx.doi.org/10.1016/j.clnu.2019.08.027DOI Listing
July 2020

Quality of Life in Children with Functional Constipation: A Systematic Review and Meta-Analysis.

J Pediatr 2019 11 6;214:141-150. Epub 2019 Aug 6.

Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Objective: To systematically review the literature on health-related quality of life (HRQoL) in children with functional constipation and to identify disease-related factors associated with HRQoL.

Study Design: The Pubmed, Embase, and PsycINFO database were searched. Studies were included if they prospectively assessed HRQoL in children with functional constipation according to the Rome criteria. Articles were excluded if patients had organic causes of constipation and if HRQoL was only assessed after successful therapeutic interventions. A meta-analysis was performed calculating sample size-weighted pooled mean and SD of HRQoL scores. The quality of the studies was also assessed.

Results: A total of 20 of 2658 studies were included, providing HRQoL data for 2344 children. Quality of evidence was considered to be poor in 9 of the 20 studies (45%); 13 of the 20 studies reported sufficient data to be included in the meta-analysis. Pooled total HRQoL scores of children with functional constipation were found to be lower compared with healthy reference samples (65.6 vs 86.1; P < .01). Similar HRQoL scores were found according to self-report and parent proxy report. Hospital-based studies reported lower HRQoL scores as compared with community-based studies. Two studies reported on HRQoL scores of children with and without fecal incontinence, but no significant difference was found.

Conclusions: HRQoL is compromised in children with functional constipation.
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http://dx.doi.org/10.1016/j.jpeds.2019.06.059DOI Listing
November 2019

Diagnosis and management of children with Blue Rubber Bleb Nevus Syndrome: A multi-center case series.

Dig Liver Dis 2019 11 26;51(11):1537-1546. Epub 2019 Jul 26.

Centre of Paediatric Gastroenterology, Sheffield Children's Hospital, Sheffield, United Kingdom.

Background: Blue Rubber Bleb Nevus Syndrome (BRBNS) is a rare, severe, sporadically occurring disorder characterized by multiple venous malformations.

Aims: To present and analyze a case series of pediatric patients with BRBNS and to describe diagnostic approaches and management options applied.

Patients And Methods: Multicenter, retrospective study, evaluating the diagnosis and management of children with BRBNS.

Results: Eighteen patients diagnosed with BRBNS were included. Cutaneous venous malformations were observed in 78% and gastrointestinal venous malformations in 89%. Lesions were also found in other organs including muscles, joints, central nervous system, eyes, parotid gland, spine, kidneys and lungs. Gastrointestinal lesions were more common in the small intestine than in stomach or colon. The management varied significantly among centers. Endoscopic therapy and surgical therapy alone failed to prevent recurrence of lesions. In younger children and in patients with musculoskeletal or other organ involvement, sirolimus was used with 100% success rate in our series (5 patients treated) although poor compliance with subtherapeutic sirolimus trough levels led to recurrence in a minority.

Conclusions: Considering the multi-organ involvement in BRBNS, diagnosis and management requires a multidisciplinary approach. The treatment includes conservative, medical, endoscopic and surgical options. Prospective multicenter studies are needed to identify the optimal management of this rare condition.
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http://dx.doi.org/10.1016/j.dld.2019.04.020DOI Listing
November 2019

Diagnostic Accuracy of Transabdominal Ultrasound in Detecting Intestinal Inflammation in Paediatric IBD Patients-a Systematic Review.

J Crohns Colitis 2019 Dec;13(12):1501-1509

Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology, Amsterdam, The Netherlands.

Background And Aims: Currently used non-invasive tools for monitoring children with inflammatory bowel disease [IBD], such as faecal calprotectin, do not accurately reflect the degree of intestinal inflammation and do not provide information on disease location. Ultrasound [US] might be of added value. This systematic review aimed to assess the diagnostic test accuracy of transabdominal US in detecting intestinal inflammation in children with IBD in both diagnostic and follow-up settings.

Methods: We systematically searched PubMed, Embase [Ovid], Cochrane Library, and CINAHL [EBSCO] databases for studies assessing diagnostic accuracy of transabdominal US for detection of intestinal inflammation in patients diagnosed or suspected of IBD, aged 0-18 years, with ileo-colonoscopy and/or magnetic resonance enterography [MRE] as reference standards. Studies using US contrast were excluded. Risk of bias was assessed with QUADAS-2.

Results: The search yielded 276 records of which 14 were included. No meta-analysis was performed, because of heterogeneity in study design and methodological quality. Only four studies gave a clear description of their definition for an abnormal US result. The sensitivity and specificity of US ranged from 39-93% and 90-100% for diagnosing de novo IBD, and 48-93% and 83-93% for detecting active disease during follow-up, respectively.

Conclusions: The diagnostic accuracy of US in detecting intestinal inflammation as seen on MRE and/or ileo-colonoscopy in paediatric IBD patients remains inconclusive, and there is currently no consensus on defining an US result as abnormal. Prospective studies with adequate sample size and methodology are needed before US can be used in the diagnostics and monitoring of paediatric IBD.
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http://dx.doi.org/10.1093/ecco-jcc/jjz085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142400PMC
December 2019

Definitions of Pediatric Functional Abdominal Pain Disorders and Outcome Measures: A Systematic Review.

J Pediatr 2019 09 2;212:52-59.e16. Epub 2019 Jul 2.

Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology, Amsterdam, the Netherlands.

Objective: To systematically review definitions of functional abdominal pain orders (FAPDs) and outcome measures used in therapeutic randomized controlled trials in pediatric FAPDs adhering to the Outcome Measures in Rheumatology recommendations.

Study Design: Cochrane, MEDLINE, Embase, and Cinahl databases were systematically searched from inception to April 2018. English-written therapeutic randomized controlled trials concerning FAPDs in children aged 4-18 years were included. Definitions of FAPDs, interventions, outcome measures, measurement instruments, and outcome assessors of each study were tabulated descriptively. Quality was assessed using the Delphi List.

Results: A total of 4771 articles were found, of which 64 articles were included (n = 25, 39% of high methodologic quality). The Rome III (50%), Rome II (17%), Apley (16%), and author-defined (17%) criteria were used to define FAPDs. Fourteen studies (22%) assessed a pharmacologic, 25 (39%) a dietary, and 25 (39%) a psychosocial intervention. Forty-four studies (69%) predefined their primary outcomes. In total, 211 reported predefined outcome measures were grouped into 23 different outcome domains; the majority being patient-reported (n = 27, 61%). Of the 14 studies that evaluated a pharmacologic intervention, 12 (86%) reported on adverse events.

Conclusions: Studies on pediatric FAPDs are of limited methodologic quality and show large heterogeneity and inconsistency in defining FAPDs and outcome measures used. Development of a core outcome set is needed to make comparison between intervention studies possible.
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http://dx.doi.org/10.1016/j.jpeds.2019.04.048DOI Listing
September 2019

Prevalence of Gastroesophageal Reflux Disease Symptoms in Infants and Children: A Systematic Review.

J Pediatr Gastroenterol Nutr 2019 06;68(6):811-817

Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital/Amsterdam UMC.

Objectives: Gastroesophageal reflux disease (GERD) is defined as gastroesophageal reflux causing troublesome symptoms or complications. In this study we reviewed the literature regarding the prevalence of GERD symptoms in infants and children.

Methods: Databases of PubMed, EMBASE, and Cochrane were systematically searched from inception to June 26, 2018. English-written studies based on birth cohort, school-based, or general population samples of ≥50 children aged 0 to 21 years were included. Convenience samples were excluded.

Results: In total, 3581 unique studies were found, of which 25 studies (11 in infants and 14 in children) were included with data on the prevalence of GERD symptoms comprising a total population of 487,969 children. In infants (0-18 months), GERD symptoms are present in more than a quarter of infants on a daily basis and show a steady decline in frequency with almost complete disappearance of symptoms at the age of 12 months. In children older than 18 months, GERD symptoms show large variation in prevalence between studies (range 0%-38% of study population) and overall, are present in >10% and in 25% on respectively a weekly and monthly basis. Of the risk factors assessed, higher body mass index and the use of alcohol and tobacco were associated with higher GERD symptom prevalence.

Conclusions: This systematic review demonstrates that the reported prevalence of GERD symptoms varies considerably, depending on method of data collection and criteria used to define symptoms. Nevertheless, the high reported prevalence rates support better investment of resources and educational campaigns focused on prevention.
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http://dx.doi.org/10.1097/MPG.0000000000002280DOI Listing
June 2019

Development of a Core Outcome Set for Infant Gastroesophageal Reflux Disease.

J Pediatr Gastroenterol Nutr 2019 05;68(5):655-661

Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology, Amsterdam, The Netherlands.

Objective: In therapeutic trials for infant gastroesophageal reflux disease (GERD), ways to define GERD and measure and report study outcomes vary widely. The aim of this study was to develop a core outcome set (COS) for infant GERD.

Methods: The COS was developed using the Delphi technique, adhering to the Outcome Measures in Rheumatology Initiative 2.0 recommendations. Healthcare professionals (HCPs) (predominantly pediatric gastroenterologists and general pediatricians) and parents of infants (age 0-12 months) with GERD, listed up to 5 primary goals of therapy from their perspective and up to 5 persistent signs or symptoms that would signify inadequate treatment. Outcomes mentioned by >10% of participants were included in 2 shortlists. Next, HCPs and parents rated and prioritized outcomes on these shortlists. Outcomes with the highest rank formed the draft COS. The final COS was created after 2 consensus meetings between an expert panel and patient representatives.

Results: In total, 125 of 165 HCPs (76%) and 139 of 143 parents (97%) of infants with GERD completed the first phase. The second phase was completed by 83 of 139 HCPs (60%) and 127 of 142 different parents (89%). Outcomes of these phases were discussed during the consensus meetings and a 9-item COS was formed: "Adequate Growth," "Adequate Relief," "Adverse events,", "Crying," "Evidence of Esophagitis," "Feeding Difficulties," "Hematemesis," "No Escalation of Therapy," and "Sleep Problems."

Conclusions: We developed a COS for infant GERD consisting of 9 items that should minimally be measured in future therapeutic trials to decrease study heterogeneity and ease comparability of results.
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http://dx.doi.org/10.1097/MPG.0000000000002245DOI Listing
May 2019

Body Composition Using Air Displacement Plethysmography in Children With Intestinal Failure Receiving Long-Term Home Parenteral Nutrition.

JPEN J Parenter Enteral Nutr 2020 02 22;44(2):318-326. Epub 2019 Mar 22.

Department of Pediatric Gastroenterology, Erasmus Medical Center - Sophia Children's Hospital, Rotterdam, the Netherlands.

Background: Children with intestinal failure (IF) are at risk of growth failure, but little information about body composition is available. Our aim was to assess body composition using air displacement plethysmography (ADP) and relate it to clinical and growth parameters.

Methods: In this prospective descriptive observational 2-center cohort study, children aged 2-18 years receiving home parenteral nutrition (PN) for ≥6 months underwent ADP measurement. Fat mass index (FMI) and fat-free mass index (FFMI) standard deviation scores (SDSs) were calculated to normalize for small body size.

Results: Twenty-one out of 22 children, median age 7.4 years, underwent successful ADP measurement after a median PN duration of 5.5 years. They were significantly lighter (median weight for age SDS -0.71, P = 0.004) and shorter (median height for age SDS -1.55, P < 0.001) than the normal population mean; 52% were growing below target height range. They had low FFMI (median SDS -1.53, P < 0.001) and high FMI (median SDS 0.80, P = 0.002). Weight for height and body mass index (BMI) were significantly associated with FFMI and BMI with FMI, but children with the same weight and height showed different body composition. In 13 patients with 1-year follow-up, growth and body composition did not change significantly.

Conclusion: Children with IF receiving long-term PN show lower FFM and higher FM than healthy children. Additionally, children with similar routine growth parameters showed different body composition. Further studies should evaluate the effect of a patient-tailored approach including physical activity and nutrition advice based on body composition.
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http://dx.doi.org/10.1002/jpen.1527DOI Listing
February 2020

Side effects associated with pharmacotherapy for pediatric irritable bowel syndrome and functional abdominal pain - not otherwise specified: a systematic review.

Expert Opin Drug Saf 2019 Feb 5;18(2):111-125. Epub 2019 Feb 5.

a Pediatric Gastroenterology , Emma Children's Hospital, Amsterdam UMC, University of Amsterdam , Amsterdam , The Netherlands.

Introduction: To systematically review the literature regarding the side effects of pharmacotherapy in children with irritable bowel syndrome (IBS) and functional abdominal pain - not otherwise specified (FAP-NOS). Areas covered: Cochrane Library, PubMed, and Embase databases were searched from inception to May 2018. The following inclusion criteria were applied: (1) randomized controlled trials (RCTs), cohort studies or case-control studies; (2) in children aged 4-18 years or adult studies if children are reported separately; (3) reporting a diagnosis of IBS or FAP-NOS as defined by the authors; and (4) reporting the occurrence of side effects of pharmacotherapy. Quality assessment of included studies was conducted. Expert opinion: A total of 4619 articles were identified; 17 were included. In 10/17 (59%) studies, side effects of pharmacotherapy (antispasmodics, antidepressants, antihistaminic agents, serotonergic agents and antibiotics) occurred. The majority of side effects were: (1) limited to the gastrointestinal tract and central nervous system and, 2) mild and transient. No serious adverse events were reported. This systematic review shows that data on safety in children with functional abdominal pain disorders are scarce, and highlights the lack of high-quality research for potential side effects of pediatric IBS and FAP-NOS. Further research by means of large well-designed-follow-up studies is necessary.
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http://dx.doi.org/10.1080/14740338.2019.1574295DOI Listing
February 2019

Pharmacological treatments for functional nausea and functional dyspepsia in children: a systematic review.

Expert Rev Clin Pharmacol 2018 Dec 6;11(12):1195-1208. Epub 2018 Dec 6.

a Emma Children's Hospital, Amsterdam UMC , University of Amsterdam, Pediatric Gastroenterology , Amsterdam , The Netherlands.

Introduction: Chronic idiopathic nausea (CIN) and functional dyspepsia (FD) cause considerable strain on many children's lives and their families. Areas covered: This study aims to systematically assess the evidence on efficacy and safety of pharmacological treatments for CIN or FD in children. CENTRAL, EMBASE, and Medline were searched for Randomized Controlled Trials (RCTs) investigating pharmacological treatments of CIN and FD in children (4-18 years). Cochrane risk of bias tool was used to assess methodological quality of the included articles. Expert commentary: Three RCTs (256 children with FD, 2-16 years) were included. No studies were found for CIN. All studies showed considerable risk of bias, therefore results should be interpreted with caution. Compared with baseline, successful relief of dyspeptic symptoms was found for omeprazole (53.8%), famotidine (44.4%), ranitidine (43.2%) and cimetidine (21.6%) (p = 0.024). Compared with placebo, famotidine showed benefit in global symptom improvement (OR 11.0; 95% CI 1.6-75.5; p = 0.02). Compared with baseline, mosapride versus pantoprazole reduced global symptoms (p = 0.011; p = 0.009). One study reported no occurrence of adverse events. This systematic review found no evidence to support the use of pharmacological drugs to treat CIN or FD in children. More high-quality clinical trials are needed.

Abbreviations: AP-FGID: Abdominal Pain Related Functional Gastrointestinal Disorders; BART: Biofeedback-Assisted Relaxation Training; CIN: Chronic Idiopathic Nausea; COS: Core Outcomes Sets; EPS: Epigastric Pain Syndrome; ESPGHAN: European Society for Pediatric Gastroenterology Hepatology and Nutrition; FAP: Functional Abdominal Pain; FD: Functional Dyspepsia; GERD: Gastroesophageal Reflux Disease; GES: Gastric Electrical Stimulation; HRAs: H2 Receptor Antagonists; IBS: irritable bowel syndrome; NASPGHAN: North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; PDS: Postprandial Distress Syndrome; PPIs: Proton Pump Inhibitor; PROMs: Patient Reported Outcome Measures; RCTs: Randomized Controlled Trials; SSRIs: selective serotonin reuptake inhibitors; TCAs: tricyclic antidepressants.
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http://dx.doi.org/10.1080/17512433.2018.1540298DOI Listing
December 2018

ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Home parenteral nutrition.

Clin Nutr 2018 12 18;37(6 Pt B):2401-2408. Epub 2018 Jun 18.

Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

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http://dx.doi.org/10.1016/j.clnu.2018.06.954DOI Listing
December 2018

Health-related quality of life, anxiety, depression and distress of mothers and fathers of children on Home parenteral nutrition.

Clin Nutr 2019 08 2;38(4):1905-1912. Epub 2018 Jul 2.

Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital AMC, Amsterdam, The Netherlands. Electronic address:

Background & Aims: Parents of children with intestinal failure, dependent on Home Parenteral Nutrition (HPN), may experience psychosocial problems due to the illness and intensive treatment of their child. Literature concerning psychosocial problems is scarce. Therefore, we aimed to investigate Health-Related Quality of Life (HRQOL), levels of anxiety, depression, distress and everyday problems of these mothers and fathers.

Methods: A multicenter study was conducted among 37 mothers and 25 fathers of 37 children on HPN (response-rate 37/49 = 76%, mean age children = 5.1 years, SD = 4.6). Parents completed three questionnaires to measure different outcomes on the KLIK website (www.hetklikt.nu): the TNO-AZL QOL Questionnaire (TAAQOL) to measure HRQOL, the Hospital Anxiety and Depression Scale (HADS) to measure anxiety and depression, and the Distress Thermometer for Parents (DT-P) to measure distress. Scores were compared to Dutch reference mothers and fathers using Mann-Whitney U-tests.

Results: No differences were found in HRQOL, measured by the TAAQOL, between HPN parents compared to the reference groups, except for the subscale 'depressive emotions' for mothers (p = .01) and 'daily activities' for fathers (p = .04). HPN mothers reported higher levels of depression compared to reference mothers (p = .001). In addition, HPN mothers and fathers reported higher levels of distress than reference mothers (p = .001) and fathers (p = .03). HPN mothers reported significantly more problems in the practical, emotional, cognitive and parenting domains, fathers in the social, emotional and parenting domains.

Conclusions: On HRQOL, anxiety and depression, HPN parents generally did not show much differences compared to reference parents. However, when asked about parental distress and everyday problems, HPN treatment of their child seems highly stressful for some parents and influences daily functioning. Therefore, structural screening for parental psychosocial problems in clinical practice, e.g. using the DT-P, is necessary in order to improve the well-being of both these parents and their children dependent on HPN.
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http://dx.doi.org/10.1016/j.clnu.2018.06.981DOI Listing
August 2019

A Multifaceted Intervention to Reduce Pediatric Acid-Suppressant Prescriptions for Gastroesophageal Reflux: What Have We Learned?

J Pediatr Gastroenterol Nutr 2018 11;67(5):605-609

Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital.

Objective: Acid-suppressant prescriptions for children have increased over past decades, despite guideline recommendations to prescribe prudently. Acid suppressants are often ineffective and may lead to side effects. We aimed to reduce inappropriate acid-suppressant prescriptions for gastroesophageal reflux in a tertiary care setting through active implementation of national guideline recommendations and to evaluate intervention effect.

Methods: Implementation consisted of 2 steps. First, all pediatric clinicians in an academic hospital received information on appropriate acid-suppressant prescribing, a link to an online national guideline application and summary card with important evidence-based recommendations-Wise Choices. Hereafter, clinicians prescribing acid suppressants were contacted to provide feedback on indications and to assess their knowledge of the guideline and Wise Choices. The pharmacy database supplied prescription data before, during, and after this intervention.

Results: During the study period prescriptions ranged from 115 to 201/month. Ten months postintervention, a nonsignificant decrease of 4 prescriptions/month was measured (95% confidence interval -49-41). Of the 78 prescribers 76 were successfully contacted: 63% were familiar with the guideline and 45% with Wise Choices. Thirty percent of prescriptions were for gastroesophageal reflux symptoms.

Conclusion: This multifaceted implementation strategy did not lead to a significant difference in acid-suppressant prescriptions by tertiary care clinicians of whom the majority was familiar with the gastroesophageal reflux disease guideline. Future studies should clarify, which implementation strategies are most effective in reducing inappropriate prescribing of acid suppressants for children. Uniform registration of prescriptions and indications in a national database will enable monitoring of the intervention effect.
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http://dx.doi.org/10.1097/MPG.0000000000002054DOI Listing
November 2018

Effectiveness of Probiotics in Children With Functional Abdominal Pain Disorders and Functional Constipation: A Systematic Review.

J Clin Gastroenterol 2018 Nov/Dec;52 Suppl 1, Proceedings from the 9th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition & Human and Microbiota Health Meeting, held in Rome, Italy from September 10 to 12, 2017:S10-S26

Department of Pediatric Gastroenterology and Nutrition, Emma's Children's Hospital Academic Medical Center, Amsterdam, The Netherlands.

Objective: The objective of this study was to investigate the effect of probiotics on functional abdominal pain disorders (FAPD) and functional constipation (FC).

Methods: A systematic review was conducted, searching PubMed and Cochrane databases from inception to January 2018 for randomized controlled trials (RCTs) investigating the efficacy of probiotics in children aged 4 to 18 years with FAPD or children aged 0 to 18 years with FC.

Results: A total of 657 citations were identified. Finally, 11 RCTs for FAPD and 6 RCTs for FC were included. Some evidence exists for Lactobacillus rhamnosus GG (n=3) in reducing frequency and intensity of abdominal pain in children with irritable bowel syndrome. There is no evidence to recommend L. reuteri DSM 17938 (n=5), a mix of Bifidobacterium infantis, Bifidobacterium breve and Bifidobacterium longum (n=1), Bifidobacterium lactis (n=1) or VSL#3 (n=1) for children with FAPD. No evidence exists to support the use of Lactobacillus casei rhamnosus LCR35 (n=1), B. lactis DN173 010 (n=1), B. longum (n=1), L. reuteri DSM 17938 (n=1), a mix of B. infantis, B. breve and B. longum (n=1), or Protexin mix (n=1) for children with FC. In general, studies had an unclear or high risk of bias.

Conclusions: Insufficient evidence exists for the use of probiotics in FAPD and FC, only L. rhamnosus GG seems to reduce frequency and intensity of abdominal pain but only in children with irritable bowel syndrome. A better understanding of differences in gut microbiota in health and disease might lead to better probiotic strategies to treat disease.
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http://dx.doi.org/10.1097/MCG.0000000000001054DOI Listing
October 2019

Prevalence of Functional Defecation Disorders in Children: A Systematic Review and Meta-Analysis.

J Pediatr 2018 07 12;198:121-130.e6. Epub 2018 Apr 12.

Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.

Objective: To systematically review the literature regarding the epidemiology of functional constipation and functional nonretentive fecal incontinence (FNRFI) in children. Secondary objectives were to assess the geographical, age, and sex distribution of functional constipation and FNRFI and to evaluate associated factors.

Study Design: The Cochrane Library, PubMed, and Embase databases were searched from 2006 until September 2017. The following inclusion criteria were applied: (1) prospective studies of population-based samples; (2) reporting on the prevalence of functional constipation or FNRFI according to the Rome III/IV criteria; (3) in children aged 0-18 years; and (4) published in full manuscript form. A quality assessment of included studies was conducted. Random effect meta-analyses with meta-regression analyses of study characteristics were performed.

Results: Thirty-seven studies were included, of which 35 reported on the prevalence of functional constipation and 15 of FNRFI. The reported prevalence of functional constipation ranged from 0.5% to 32.2%, with a pooled prevalence of 9.5% (95% CI 7.5-12.1). The prevalence of FRNFI ranged from 0.0% to 1.8%, with a pooled prevalence of 0.4% (95% CI 0.2-0.7). The prevalence of functional constipation was 8.6% in boys compared with 8.9% in girls (OR 0.99, 95% CI 0.9-1.4). Geographical location, dietary habits, and exposure to stressful life events were reported to be associated with the prevalence of functional constipation. Data on FNRFI were scarce and no associated factors were identified.

Conclusion: Functional constipation is common in childhood and is associated with geographical location, lifestyle factors, and stressful life events. FNRFI is rare, and no associated factors were identified.
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http://dx.doi.org/10.1016/j.jpeds.2018.02.029DOI Listing
July 2018