Effect of Mirtazapine on Nausea in Children with Functional Nausea and Functional Dyspepsia Postprandial Distress Syndrome.

OBJECTIVE: The objective of this study was to assess the clinical response and safety of mirtazapine in the pediatric population with a diagnosis of functional nausea and nausea associated with functional dyspepsia postprandial distress syndrome. METHODS: This was a retrospective chart review to evaluate the safety and efficacy of mirtazapine for pediatric nausea and nausea associated with functional dyspepsia postprandial distress syndrome. Clinical response was classified as complete response, partial response, and no response. We also identified the prescribed doses, side effects, and weight changes during mirtazapine therapy. RESULTS: Among the 57 total patients, 67% were females and ages ranged from 7 to 19 years with a mean of 14 ± 3 years. Clinical (complete and partial) response was reported in 82% of patients. Nausea resolved in 82% and insomnia in 77% of the patients. Eighty-four percent gained weight with a mean of 4 ± 7 kg. Sixty-five percent did not report adverse effects. The most common adverse effects were undesired weight gain (16%) and dysphoria (9%). Two patients discontinued the medicine after the first dose because of adverse effects. There was a significant correlation between the initial dose and weight (rs = 0.478; p = 0.0002). The median initial and final doses were 15 mg, respectively. CONCLUSIONS: Mirtazapine is an option for treating children and adolescents with functional nausea and nausea associated with functional dyspepsia post-prandial distress syndrome, especially for a select group of patients with concurrent weight loss, anxiety, and insomnia.

iKanEat: protocol for a randomized controlled trial of megestrol as a component of a pediatric tube weaning protocol.

BACKGROUND: Although tube feeding routinely saves the lives of children who do not eat by mouth, chronic tube feeding can be a burden to patients, caregivers, and families. Very few randomized trials exist regarding the best methods for weaning children from their feeding tubes. METHODS: The current paper describes a randomized controlled trial of an empirically supported outpatient treatment protocol for moving children from tube to oral eating called iKanEat. Specifically, we describe the methods of randomized double-blind, placebo-controlled trial which includes a 4-week course of megestrol, the only medication used in the iKanEat protocol, to determine whether the addition of megestrol results in improved child outcomes. The primary and secondary aims are to assess the safety and efficacy of megestrol as part of the iKanEat protocol. The third aim is to provide critical information about the impact of the transition from tube to oral feeding on parent stress and parent and child quality of life. DISCUSSION: This trial will provide data regarding whether megestrol is a safe and effective component of the iKanEat tube weaning protocol, as well as important data on how the tube weaning process impacts parent stress and parent and child quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT#03815019 . Registered on January 17, 2019.

Self-Efficacy in Children with Functional Constipation Is Associated with Treatment Success.

OBJECTIVES: To assess the relationship between self-efficacy, the belief that an individual can succeed at a goal, and short-term treatment outcome in children with functional constipation. STUDY DESIGN: Patients with functional constipation age 8-16 years completed the Self-Efficacy for Functional Constipation Questionnaire (SEFCQ), consisting of 14 statements about performing tasks needed for defecation. Patients completed SEFCQ before, immediately after, and 3 weeks after their clinic visit. Treatment success was defined as ≥3 bowel movements into the toilet and no fecal incontinence in the third week. RESULTS: 75% of patients had a successful outcome. Scores were higher in the group that was successful than in those that failed before, immediately after the visit, and 3 weeks later (P < .001). Self-efficacy improved at all time points in the group that was successful (P < .001). In the group that failed, scores improved immediately after clinic visit (P < .01) but were unchanged at follow-up (P > .05). CONCLUSIONS: Improved self-efficacy is associated with successful outcomes in children with functional constipation, thus, it may be beneficial to enhance self-efficacy for defecation during treatment.

Serum-derived bovine immunoglobulin for children with diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Oral serum-derived bovine immunoglobulin (SBI)/protein isolate is a medical food intended to manage chronic diarrhea. It has been shown to improve pain and diarrhea in adults with diarrhea-predominant irritable bowel syndrome (d-IBS). AIM: To determine if SBI can improve symptoms in children with d-IBS. METHODS: We performed a randomized, double-blind, placebo-controlled, pilot study (NCT02609529) to evaluate the effectiveness of SBI in children 8-18 years with d-IBS. We recorded stool number, abdominal pain, and stool form in all patients for 1 week and then assigned the patients at a ratio of 2:1 to treatment with SBI 5 g BID or placebo for 3 weeks. The patients and their parents completed the Pediatric Quality of Life Inventory™ for Gastrointestinal Symptoms (PedsQOL) and the Pediatric Functional Disability Index (FDI). In addition, complete blood counts and serum chemistries were recorded at the start and end of treatment to evaluate safety. RESULTS: Fifteen patients (nine SBI, six placebo) completed the study. Both SBI and placebo groups reported nonstatistical reductions in stool frequency per week. The SBI group showed a significant reduction in stool frequency at weeks 1 and 2 but not at the end of treatment. The SBI group also demonstrated statistical improvements in abdominal pain and stool form by 3 weeks. The placebo group did not achieve similar improvements. The overall FDI and PedsQOL scores, as well as PedsQOL subscale scores for pain, discomfort when eating, diarrhea, worry about stomach aches, and communication, improved significantly in the SBI group, but not in the placebo group. No serious adverse events occurred. Serum chemistries and hemograms were normal at baseline and at the end of study in all patients. CONCLUSION: In this single-center, exploratory pilot study, we demonstrated that 10 g SBI per day was safe in children with d-IBS and improved symptoms. Larger studies, with longer treatment duration, seem warranted based on these initial positive results.

Prevalence of Pediatric Functional Gastrointestinal Disorders Utilizing the Rome IV Criteria.

OBJECTIVE: To assess the prevalence of functional gastrointestinal (GI) disorders in children 0-18 years old according to the newly established Rome IV diagnostic criteria as reported by parents in a representative community sample. STUDY DESIGN: A cross-sectional study in which mothers (n = 1255) of children aged 0-18 years old in the US were recruited to complete an online survey about their child's GI symptoms, quality of life (QoL), and other health conditions. RESULTS: Based on the Rome IV criteria, 24.7% of infants and toddlers aged 0-3 years and 25.0% of children and adolescents aged 4-18 years fulfilled symptom-based criteria for a functional GI disorder. The most common functional GI disorders were infant regurgitation among infants (24.1%) and functional constipation among both toddlers (18.5%) and children and adolescents (14.1%). QoL was diminished in pediatric patients with functional GI disorders (median = 71.69 vs median = 87.60; z = -11.41; P < .001). Children were more likely to qualify for a functional GI disorder if their parent qualified for a functional GI disorder (35.4% vs 23.0%; P < .001). CONCLUSIONS: Based on Rome IV criteria, functional GI disorders are common in pediatric populations of all ages and are associated with decreased QoL.

Rumination Syndrome and Dental Erosions in Children.

Rumination syndrome is the effortless regurgitation of recently ingested food with subsequent reswallowing or spitting out. Dental erosion (DE) affects 2% to 5% of the population. DE is defined as loss of tooth structure by a chemical process that does not involve bacteria. Our objective was to compare the frequency of DE among children with rumination syndrome with healthy controls. We enrolled 30 patients 4 to 21 years of age diagnosed with rumination syndrome, and 30 age- and sex-matched healthy control subjects. Patients were evaluated by pediatric dentists for presence of DE with Taji et al a validated grading system. Patients with rumination were more likely to have DE (P < 0.001). Of patients with rumination syndrome, 23 (77%) had DE, compared with 4 (13%) control subjects. DEs are more frequent in patients with rumination syndrome.

Biliary Dyskinesia in Children: A Systematic Review.

Cholecystectomy rates for biliary dyskinesia in children are rising in the United States, but not in other countries. Biliary dyskinesia is a validated functional gallbladder disorder in adults, requiring biliary colic in the diagnosis. In contrast, most studies in children require upper abdominal pain, absent gallstones on ultrasound, and an abnormal gallbladder ejection fraction (GBEF) on cholecystokinin-stimulated cholescintigraphy for diagnosis. We aimed to systematically review existing literature in biliary dyskinesia in children, determine the validity and reliability of diagnostic criteria, GBEF, and to assess outcomes following cholecystectomy. We performed a systematic review following the PRISMA checklist and searched 7 databases including PubMed, Scopus, Embase, Ovid, MEDLINE, ProQuest, Web of Science, and the Cochrane library. Bibliographies of articles were screened for additional studies. Our search terms yielded 916 articles of which 28 were included. Three articles were manually added from searched references. We reviewed 31 peer-reviewed publications, all retrospective chart reviews. There was heterogeneity in diagnostic criteria and GBEF values. Outcomes after laparoscopic cholecystectomy varied from 34% to 100% success, and there was no consensus concerning factors influencing outcomes. The observational, retrospective study designs that comprised our review limited interpretation of safety and efficacy of the investigations and treatment in biliary dyskinesia in children. Symptoms of biliary dyskinesia overlapped with functional dyspepsia. There is a need for consensus on symptoms defining biliary dyskinesia, validation of testing required for diagnosis of biliary dyskinesia, and randomized controlled trials comparing medical versus surgical management in children with upper abdominal pain.

Childhood Functional Gastrointestinal Disorders: Neonate/Toddler.

In 2006, a consensus concerning functional gastrointestinal intestinal disorders (FGIDs) in infants and toddlers was described. At that time little evidence regarding epidemiology, pathophysiology, diagnostic work-up, treatment strategies and follow-up was available. Consequently the criteria for the clinical entities were more experience than evidence based. In the past decade, new insights have been gained in the different FGIDs in these age groups. Based on those, further revisions have been made to the criteria. The description of infant colic has been expanded to include criteria for the general pediatrician and specific criteria for researchers. The greatest change was the addition of a paragraph regarding the neurobiology of pain in infants and toddlers, including the understanding of the neurodevelopment of nociception and of the wide array of factors that may impact the pain experience.

A Randomized Controlled Trial of an Outpatient Protocol for Transitioning Children from Tube to Oral Feeding: No Need for Amitriptyline.

OBJECTIVE: To assess the role of amitriptyline in the effectiveness of an outpatient protocol for weaning medically complicated children from tube to oral feeding. STUDY DESIGN: Twenty-one children seen in multidisciplinary outpatient feeding teams across 4 sites were recruited to a randomized placebo-controlled trial of a 6-month outpatient treatment protocol with behavioral, oral-motor, nutrition, and medication components. RESULTS: All of the children who completed the 6-month program (73%) were weaned to receive only oral feeding, regardless of group assignment. The transition from tube to oral feeding resulted in decreases in body mass index percentile and pain, some improvements in quality of life, and no statistically significant changes in cost. CONCLUSIONS: Amitriptyline is not a key component of this otherwise effective outpatient, interdisciplinary protocol for weaning children from tube to oral feeding. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01206478.

Age of Onset of Functional Constipation.

In a review of 538 children with functional constipation, we analyzed ages of presentation and onset, symptom duration, and behavioral/developmental problems. We divided the subjects into quartiles (Q1-Q4) based on age of onset. Median onset age was 2.3 years. The oldest group had the shortest symptom duration before referral at 1.8 ±â€Š1.8 years (compared with Q3 to Q1, P = 0.039, P = 0.001, P < 0.001, respectively). Of the Q4 subjects, 22% had a behavioral/developmental problem (P < 0.001 compared with Q1-Q3). We conclude that most children develop functional constipation as infants and toddlers, but those with later onset are more likely to have behavioral/developmental issues and see a specialist sooner.

Functional Gastrointestinal Disorders Dominate Pediatric Gastroenterology Outpatient Practice.

OBJECTIVES: Symptom-based diagnostic criteria have improved recognition and standardization of pediatric functional gastrointestinal disorders (FGIDs). We used Rome 3 diagnostic criteria to determine the prevalence of FGIDs in pediatric gastroenterology clinic. In the process, we developed a diagnostic questionnaire for infants and toddlers. METHODS: We enrolled new patients ≤18 years referred during 19 months to a pediatric gastroenterology clinic. Subjects or parents completed a demographic survey and a the Questionnaire on Pediatric Gastrointestinal symptoms, Rome 3 Version (if ≥4 years, or a new infant-toddler questionnaire) before their appointment. RESULTS: We acquired data from 976 subjects: 476 boys, 592 white. Of 332 subjects <4 years, 172 (52%) met diagnostic criteria for ≥1 FGIDs. Of 644 subjects ≥4 years, 486 (75%) met diagnostic criteria for ≥1 FGIDs. Thirty one (9%) subjects <4 years and 170 (26%) subjects ≥4 years met the criteria for ≥2 FGIDs. Of the total sample of subjects <4 years, common FGIDs included functional constipation (29%), infant regurgitation (13%), and cyclic vomiting syndrome (10%). Of the total sample of subjects ≥4 years, common FGIDs included irritable bowel syndrome (36%), abdominal migraine (19%), functional constipation (17%), cyclic vomiting syndrome (8%), functional abdominal pain syndrome (7%), aerophagia (7%), and functional dyspepsia (7%). CONCLUSIONS: More than half of new pediatric gastrointestinal clinic patients met the Rome 3 criteria for ≥1 FGIDs. Satisfying the criteria may facilitate diagnosis on the first visit.

Development and Validation of a Rome III Functional Gastrointestinal Disorders Questionnaire for Infants and Toddlers.

OBJECTIVE: Functional gastrointestinal disorders (FGIDs) in infants and toddlers are common, but no questionnaire is available for use in clinic and research. The purpose of the present study was to develop and validate a questionnaire assessing symptoms associated with FGIDs in infants and toddlers. METHODS: Questions were developed based on the Rome III diagnostic criteria for FGIDs. A group of parents of children with FGIDs and experts in FGID reviewed the questionnaire for content, understandability, and completeness (face validity). Initial content validity was established by comparing physician and questionnaire diagnoses in a group of 332 consecutive new patients at a tertiary care clinic. RESULTS: Ten parents and 8 experts identified no major problems, indicating good face validity. Of 332 consecutive new patients, age 1 month to 4 year of age, 172 subjects (52% of the sample) qualified for a FGID by parent responses to the questionnaire (mean age = 1.23 year, 53% girls). All of these subjects also received an FGID diagnosis by their physician. Agreement between parent and doctor was fair to substantial (κ = 0.18-0.76), except for infant rumination and functional diarrhea in infants, which showed poor overlap. CONCLUSIONS: The newly developed Rome III questionnaire for infants and toddlers had good initial face and content validity. This questionnaire will be an important addition to clinical care and research of infant/toddler FGIDs. Replication of these findings in primary care is needed.

Eliminating Rumination in Developmentally Disabled Children: A Case Report.

Rumination is the effortless regurgitation of food, with subsequent spitting out or rechewing and reswallowing. In developmentally delayed children, rumination is a pleasurable, self-stimulating habit. For 3 years, we evaluated and treated 2 nonambulatory, nonverbal 4-year-old children who ruminated frequently while awake. The social isolation caused by a child covered in regurgitated food prompted caregivers of these children to find a solution. We hypothesized that rumination would cease if the stomach stayed empty of food. We intervened by placing gastrojejunostomy tubes and then initiated continuous drip jejunal tube feedings over 12 waking hours to reduce hunger; the children's oral diet was also stopped. In both cases, these changes reduced episodes of rumination to 3 to 5 times daily. To eliminate rumination, unpleasant tasting substances (N-acetylcysteine or cayenne pepper-based hot sauce) were given through the gastrostomy tube every 4 hours while the children were awake. Within 1 week of adding the unpalatable substances, rumination ceased. After 2 months of no rumination, 1 mother restarted oral feeding. There was no recurrence of rumination, and 3 months after gastrojejunal tube placement, the tube was removed. In 1 year of follow-up, rumination did not recur. The second mother was pleased with the outcome with jejunal feedings and chose not to resume oral feedings. These results showed that jejunal tube feeding in combination with insertion of unpalatable contents into the stomach eliminated rumination in these developmentally delayed children.

Disability in Children and Adolescents With Irritable Bowel Syndrome and/or Fibromyalgia.

To compare disability and emotional health in individuals with irritable bowel syndrome (IBS), fibromyalgia, or both, patients completed the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III, childhood Functional Disability Inventory (FDI), and the Behavior Assessment System for Children, Second Edition. Patients' (age range 8-18 years, 19 IBS, 12 fibromyalgia, and 12 both) FDI scores showed greater disability than scores from historically healthy patients. Fibromyalgia (FDI 22.5 ±â€Š12.7, P = 0.018) and patients with both (FDI 26.2 ±â€Š13.8, P = 0.001) averaged greater disability than those with IBS (FDI 10.6 ±â€Š7.9). Disability was correlated with anxiety and depression symptoms. Disability and psychological symptoms are important when evaluating individuals with fibromyalgia and IBS.

Prevalence of functional gastrointestinal disorders in infants and toddlers.

OBJECTIVES: To determine the prevalence of gastrointestinal symptoms suggestive of an infant/toddler functional gastrointestinal disorder (FGID) as reported by parents in a representative community sample. STUDY DESIGN: Mothers (n = 320) of children aged 0-3 years old were recruited in the US and completed a questionnaire about their child's and their own gastrointestinal symptoms. RESULTS: By Rome criteria, 27% of infants/toddlers qualified for FGIDs. Infant regurgitation was the most common disorder in infants and functional constipation in toddlers. No age, sex, or race differences were found in FGID diagnoses. Compared with those who did not meet Rome criteria, toddlers with FGID had lower quality of life (M = 80.1 vs M = 90.3, P < .001), increased medical visits (M = 0.38 vs 0.14; P < .05), mental health visits (M = 0.29 vs 0.06; P < .05), and hospital stays (M = 0.35 vs 0.06; P < .01). A child was more likely to suffer from hard stools if the parent also reported hard stools (P = .02), but similar association was not found with loose stools. CONCLUSIONS: FGIDs are common in infants and toddlers and can be identified in the general population. They do not vary with sex and race. Quality of life is reduced in those with FGIDs. More research is needed into these largely neglected conditions as it may improve the lives of a significant number of young children.

Psychotropic medications for pediatric functional gastrointestinal disorders.

We describe the use of psychotropic medications in the treatment of functional gastrointestinal disorders (FGIDs) in children based on available data. We address their safety and efficacy. Most pediatric gastroenterologists do not or are not able to collaborate with child psychiatrists, so it may be beneficial for pediatric gastroenterologists to have a working knowledge of off-label psychotropic drugs to improve functional symptoms. We recommend that efforts be made to involve both the children and their families from the beginning, adverse effects be mentioned, and the treatment plan be explained.

Lubiprostone for the treatment of functional constipation in children.

OBJECTIVES: Pediatric functional constipation is common; effective, easily administered treatment options are limited. Lubiprostone is an oral chloride channel protein-2 activator that stimulates gastrointestinal fluid secretion, softens stools, and facilitates bowel movements (BMs). We evaluated the safety and effectiveness of lubiprostone in children and adolescents with functional constipation. METHODS: Patients ≥12 kg, 17 years or younger, and with <3 spontaneous BMs (SBMs; ie, BMs that did not occur within 24 hours of rescue medication use) per week were enrolled at 22 US general pediatric and pediatric gastroenterology centers (January 2007-October 2008). Patients received 4 weeks of open-label lubiprostone at doses of 12 µg once daily (QD), 12 µg twice daily (BID), or 24 µg BID based on age and weight. The primary endpoint was SBM frequency during week 1 versus baseline. RESULTS: Of 127 enrolled patients, 124 were treated and analyzed (12 µg QD, n = 27; 12 µg BID, n = 65; 24 µg BID, n = 32), and 109 completed the study. The mean age of treated patients was 10.2 years (range 3-17 years); 65 were boys. Mean SBM frequency significantly increased compared with baseline at week 1 (3.1 vs. 1.5 SBMs/week, P < 0.0001). SBM frequency was improved significantly from baseline overall (P < 0.0001) and for individual dose groups (P ≤ 0.0062) during weeks 2, 3, and 4. Common (≥5%) adverse events included nausea (18.5%), vomiting (12.1%), diarrhea (8.1%), abdominal pain (7.3%), and headache (5.6%). Two patients experienced serious adverse events (unrelated abdominal pain; unrelated sickle cell crisis). CONCLUSIONS: Lubiprostone was efficacious and well tolerated in children and adolescents with functional constipation.