title: Pharmacological interventions on early functional gastrointestinal disorders.
abstract: BACKGROUND
  Functional gastrointestinal disorders (FGIDs) are chronic or recurrent gastrointestinal symptoms without structural or biochemical abnormalities. FGIDs are multifactorial conditions with different pathophysiologic mechanisms including altered motility, visceral hyperalgesia, brain-gut disturbance, genetic, environmental and psychological factors. Although in most cases gastrointestinal symptoms are transient and with spontaneous resolution in infancy multiple dietary changes and pharmacological therapy are often started despite a lack of evidence-based data. Our aim was to update and critically review the current literature to assess the effects and the clinical appropriateness of drug treatment in early (occurring in infants and toddlers) FGIDs.
  
  
  METHODS
  We systematically searched the Medline and GIMBE (Italian Group on Medicine Based on Evidence) databases, according to the methodology of the Critically Appraised Topics (CATs). We included reviews, clinical studies, and evidence-based guidelines reporting on pharmacological treatments. Systematic reviews and randomized controlled trials (RCTs) concerning pharmacologic therapies in children with early FGIDs were included, and data were extracted on participants, interventions, and outcomes.
  
  
  RESULTS
  We found no evidence-based guidelines or systematic reviews about the utility of pharmacological therapy in functional regurgitation, infant colic and functional diarrhea. In case of regurgitation associated with marked distress, some evidences support a short trial with alginate when other non pharmacological approach failed (stepped-care approach). In constipated infants younger than 6 months of age Lactulose is recommended, whilst in older ages Polyethylene glycol (PEG) represents the first-line therapy both for fecal disimpaction and maintenance therapy of constipation. Conversely, no evidence supports the use of laxatives for dyschezia. Furthermore, we found no RCTs regarding the pharmacological treatment of cyclic vomiting syndrome, but retrospective studies showed a high percentage of clinical response using cyproheptadine, propanolol and pizotifen.
  
  
  CONCLUSIONS
  There is some evidence that a pharmacological intervention is necessary for rectal disimpaction in childhood constipation and that PEG is the first line therapy. In contrast, for the other early FGIDs there is a lack of well-designed high-quality RCTs and no evidence on the use of pharmacological therapy was found.
authors.affiliation: Department of Experimental and Clinical Medicine, Pediatrics, University of Insubria, Varese, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Salvatore
authors.affiliation: Department of Pediatrics, Fatebenefratelli Hospital, Milan, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Barberi
authors.affiliation: Division of Neurogastroenterology and Motility, Department of Pediatric Gastroenterology, UCL Institute of Child Health and Great Ormond Street Hospital, London, UK.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Borrelli
authors.affiliation: Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Castellazzi
authors.affiliation: Department of Clinical and Experimental Medicine, Pediatric Unit, University of Parma, Parma, Italy.
authors.forename: Dora
authors.initials: D
authors.lastname: Di Mauro
authors.affiliation: President Italian Society of Preventive and Social Pediatrics (SIPPS), Primary Care Pediatrician, Caserta, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Mauro
authors.affiliation: Primary Care Pediatrics, Milan, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Doria
authors.affiliation: Interdisciplinary Department of Medicine-Pediatric Section, University of Bari, Bari, Italy.|Department of Pediatrics, San Paolo Hospital, Bari, Italy.
authors.forename: Ruggiero
authors.initials: R
authors.lastname: Francavilla
authors.affiliation: National Pediatric Healthcare System, Turin, Italy.|Unit Research of Pediatric Pulmonology and Allergy Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council, Palermo, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Landi
authors.affiliation: Pediatric Department, Garbagnate Santa Corona Hospital, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Martelli
authors.affiliation: Department of Pediatrics, Aldo Moro University of Bari, Giovanni XXIII Hospital, Bari, Italy.
authors.forename: Vito Leonardo
authors.initials: VL
authors.lastname: Miniello
authors.affiliation: Primary Care Pediatrics, ASL Brindisi, Mesagne, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Simeone
authors.affiliation: Department of Pediatrics, San Paolo Hospital, Department of Health Science, University of Milan, Milan, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Verduci
authors.affiliation: Primary Care Pediatrics, ASL Salerno, Vietri sul Mare, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Verga
authors.affiliation: Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
authors.forename: Maria Assunta
authors.initials: MA
authors.lastname: Zanetti
authors.affiliation: Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy. staiano@unina.it.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Staiano
mesh_terms: D002648:Child; D002675:Child, Preschool; D003085:Colic / Q000175:diagnosis / Q000188:drug therapy; D003248:Constipation / Q000175:diagnosis / Q000188:drug therapy; D005244:Fecal Impaction / Q000175:diagnosis / Q000188:drug therapy; D005260:Female; D005764:Gastroesophageal Reflux / Q000175:diagnosis / Q000188:drug therapy; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005767:Gastrointestinal Diseases / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D007223:Infant; D008297:Male; D017410:Practice Guidelines as Topic; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014839:Vomiting / Q000175:diagnosis / Q000188:drug therapy
chemical_list: D005765:Gastrointestinal Agents
keywords: Constipation; Cyclic vomiting syndrome; Dyschezia; Functional diarrhea; Gastroesophageal reflux; Infant colic; Medication therapy management; Regurgitation; Treatment