Evaluation and Treatment of Functional Constipation in Infants and Children: Evidence-Based Recommendations from ESPGHAN and NASPGHAN

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Evaluation and Treatment of Functional Constipation in Infants and Children: Evidence-Based Recommendations from ESPGHAN and NASPGHAN CLINICAL GUIDELINE Evaluation and Treatment of Functional Constipation in Infants and Children: Evidence-Based Recommendations From ESPGHAN and NASPGHAN M.M. Tabbers, C. DiLorenzo, M.Y. Berger, C. Faure, M.W. Langendam, S. Nurko, A. Staiano, Y. Vandenplas, and M.A. Benninga ABSTRACT Results: This evidence-based guideline provides recommendations for the Background: Constipation is a pediatric problem commonly encountered by evaluation and treatment of children with functional constipation to many health care workers in primary, secondary, and tertiary care. To assist standardize and improve their quality of care. In addition, 2 algorithms medical care providers in the evaluation and management of children with were developed, one for the infants <6 months of age and the other for older functional constipation, the North American Society for Pediatric Gastro- infants and children. enterology, Hepatology, and Nutrition and the European Society for Pediatric Conclusions: This document is intended to be used in daily practice and as a Gastroenterology, Hepatology, and Nutrition were charged with the task of basis for further clinical research. Large well-designed clinical trials are developing a uniform document of evidence-based guidelines. necessary with regard to diagnostic evaluation and treatment. Methods: Nine clinical questions addressing diagnostic, therapeutic, and prognostic topics were formulated. A systematic literature search was Key Words: children, constipation, encopresis, enema, evidence-based, performed from inception to October 2011 using Embase, MEDLINE, fecal incontinence, fecal soiling, functional constipation, guideline, infants, the Cochrane Database of Systematic Reviews and Cochrane Central laxative Register of Controlled Clinical Trials, and PsychInfo databases. The approach of the Grading of Recommendations Assessment, Development (JPGN 2014;58: 258–274) and Evaluation was applied to evaluate outcomes. For therapeutic questions, quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation system. Grading the quality of evidence for the other questions was performed according to the INTRODUCTION classification system of the Oxford Centre for Evidence-Based Medicine. unctional constipation is a common problem in childhood, During 3 consensus meetings, all recommendations were discussed and with an estimated prevalence of 3% worldwide (1). In 17% to finalized. The group members voted on each recommendation, using the 40%F of children, constipation starts in the first year of life (2). nominal voting technique. Expert opinion was used where no randomized Constipation is often associated with infrequent and/or painful controlled trials were available to support the recommendation. defecation, fecal incontinence, and abdominal pain; causes signifi- cant distress to the child and family; and has a significant impact Received November 23, 2013; accepted November 25, 2013. on health care cost (3). Although constipation may have several From the Emma Children’s Hospital/Academic Medical Center, Amster- etiologies, in most children presenting with this symptom no under- dam, The Netherlands. lying medical disease responsible for the symptom can be found. The Address correspondence and reprint requests to Merit M. Tabbers, MD, North American Society for Pediatric Gastroenterology, Hepatology, PhD, Emma Children’s Hospital/Academic Medical Centre, H7-250, and Nutrition published a medical position paper in 1999, which was PO Box 22700, 1100 DD Amsterdam, The Netherlands (e-mail: updated in 2006 (search until 2004) (4). Recommendations were [email protected]). based on an integration of a comprehensive and systematic review of Drs Tabbers and DiLorenzo contributed equally to the article. the medical literature combined with expert opinion. In addition, the This article has been developed as a Journal CME Activity by NASP- National Institute for Health and Clinical Excellence (NICE) in the GHAN. Visit http://www.naspghan.org/wmspage.cfm?parm1=742 to view instructions, documentation, and the complete necessary steps United Kingdom developed a guideline in 2010, based on a best- to receive CME credit for reading this article. evidence strategy, for children with constipation in primary and Supplemental digital content is available for this article. Direct URL secondary care (5). To assist health care workers in the management citations appear in the printed text, and links to the digital files are of all of the children with constipation in primary, secondary, and provided in the HTML text of this article on the journal’s Web site tertiary care, the North American Society for Pediatric Gastroenter- (www.jpgn.org). ology, Hepatology, and Nutrition and the European Society for Guideline development was financially supported by NASPGHAN and Paediatric Gastroenterology, Hepatology, and Nutrition elected to ESPGHAN. No other support was received from industry. develop evidence-based guidelines as a joint effort. The present C.D.L. is a consultant for Janssen, Sucampo, AstraZeneca, and Ironwood. C.F. guideline provides recommendations for the diagnostic evaluation is a consultant for Sucampo. S.N. is a consultant for Janssen and Sucampo. of children presenting with constipation and the treatment of children A.S. is a consultant for Valeas and DMG Italy. Y.V. is a consultant for Biocodex and United Pharmaceuticals. M.B. is a consultant for Shire and with functional constipation. It is intended to serve as a general Sucampo. The other authors report no conflicts of interest. guideline and should not be considered a substitute for clinical Copyright # 2014 by European Society for Pediatric Gastroenterology, judgment or used as a protocol applicable to all patients. The Hepatology, and Nutrition and North American Society for Pediatric guideline is also not aimed at the management of patients with Gastroenterology, Hepatology, and Nutrition underlying medical conditions causing constipation, but rather just DOI: 10.1097/MPG.0000000000000266 for functional constipation. 258 JPGN Volume 58, Number 2, February 2014 Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited. JPGN Volume 58, Number 2, February 2014 Evaluation and Treatment of Functional Constipation in Children METHODS was subdivided into subgroups that dealt with each question separately. Questions 1 and 2 were answered based on expert Literature Search and Grading the Articles for opinions and earlier published guidelines (5–9). Questions 3 to 9 Quality of Evidence were answered using the results of systematic literature searches. The project started in September 2011 by formulating 9 Systematic literature searches were performed by a clinical clinical questions (Table 1). Seven questions were chosen based on librarian from inception to October 2011. The Embase, MEDLINE, the Dutch guidelines for functional constipation (6). In addition, 2 Cochrane Database of Systematic Reviews and Cochrane Central new questions were added to the present guidelines: questions 5 and Register of Controlled Clinical Trials, and PsychInfo databases 8. After the questions were formulated, the guidelines committee were searched. The inclusion criteria were as follows: TABLE 1. Overview of the 9 clinical questions 1. Study population consisting of children of ages 0 to 18 years in whom functional constipation was diagnosed, treated, or its Question 1: What is the definition of functional constipation? course followed. The key words used to describe constipation Question 2: What are the alarm signs and symptoms that suggest the were ‘‘constipation,’’ ‘‘obstipation,’’ ‘‘faecal/fecal inconti- presence of an underlying disease causing the constipation? nence,’’ ‘‘coprostasis,’’ ‘‘encopresis,’’ and ‘‘soiling.’’ Excluded Question 3: In the diagnosis of functional constipation in children, were the studies concerning children with organic causes of what is the diagnostic value of constipation and children with exclusively functional non- 3.1 Digital rectal examination? retentive fecal incontinence. 3.2 Abdominal radiography? 2. A clear definition of functional constipation had to be provided 3.3 CTT? by the authors. 3.4 Transabdominal rectal ultrasonography? 3. To evaluate the value of tests in diagnosing functional Question 4: Which of the following diagnostic tests should be performed constipation (question 3), we included systematic reviews in children with constipation in order to diagnose an underlying and original studies related to the diagnostic accuracy of the disease? specific tests. The reference standard for functional constipation 4.1 Laboratory investigations to diagnose (cow’s milk) allergy, celiac had to be defined by the authors in terms of findings at history disease, hypothyroidism and hypercalcemia? and physical examination. 4.2 ARM or rectal suction biopsy to diagnose HD? 4. In studies evaluating the effects of treatments or interventions 4.3 Use of barium enema to diagnose organic causes such as HD? (questions 6, 7, and 8), the following inclusion criterion was Question 5: Which of the following examinations should be used: systematic reviews of randomized controlled trials performed in children with intractable constipation to evaluate (RCTs) and/or RCTs containing at least 10 individuals per arm. pathophysiology and diagnose an underlying abnormality? 5. In studies evaluating the outcome of functional constipation 5.1 Colonic manometry (questions 4, 5, and 9), the following inclusion
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