Katja Kovacic

High Prevalence of Nausea in Children With Pain-associated Functional Gastrointestinal Disorders: Are Rome Criteria Applicable?

Objectives: The aim of the study was to determine the prevalence of nausea in pediatric patients with pain-associated functional gastrointestinal disorders (FGIDs), examine the effect on social and school functioning, and examine the applicability of pediatric Rome III criteria. Methods: A total of 221 pediatric patients (6–18 years of age) with chronic abdominal pain prospectively completed a demographic, history, and gastrointestinal symptom questionnaire adapted from the Questionnaire on Pediatric Gastrointestinal Symptoms (QPGS). The 6-item, revised Pediatric Migraine Disability Assessment Score tool was used to assess the effect of symptoms on school, home, and social disability. Rome III criteria were applied to all subjects. Results: A total of 183 patients with pain and nausea for a minimum of 2 months were identified. Ninety-six patients were studied after excluding those with vomiting and/or organic disease. Among these, 53% had nausea at least 2 times per week and 28% experienced daily nausea. Frequency of nausea was significantly correlated with poor school and social functioning, and uniquely predicted social disability beyond pain. Although 87% met adult Rome criteria for functional dyspepsia, only 29% met corresponding pediatric Rome criteria. Additionally, 22% met the criteria for irritable bowel syndrome (IBS)-diarrhea, 13% for IBS-constipation, 13% for abdominal migraine, and 31% were classified as having functional abdominal pain. Pediatric IBS-diarrhea and IBS-constipation overlapped in 5% of patients. Conclusions: Nausea is a prevalent symptom in patients with pain-associated FGIDs and correlates with poor school and social functioning. There is substantial overlap among FGIDs in children with nausea.

A multicenter study on childhood constipation and fecal incontinence: Effects on quality of life

OBJECTIVE To describe the effects of childhood functional constipation compared with functional constipation plus fecal incontinence on quality of life, evaluating effects on physical, psychosocial, and family functioning. STUDY DESIGN This prospective, multicenter study collected data from 5 regional childrens hospitals. Children meeting Rome III criteria for functional constipation were included. Parents completed the following 5 instruments: Pediatric Quality of Life Inventory (PedsQL), PedsQL-Family Impact Module, Functional Disability Inventory-Parent Version, Pediatric Inventory for Parents (PIP), and Pediatric Symptom Checklist-Parent Report. RESULTS Families of 410 children aged 2-18 years (mean [SD], 7.8 [3.5] years; 52% male) were included. Children with functional constipation+fecal incontinence had worse quality of life than children with functional constipation alone (PedsQL Total Score, P ≤ .03). Older children with functional constipation + fecal incontinence had lower quality of life than their younger counterparts (PedsQL Total Score, P ≤ .047). Children with functional constipation+fecal incontinence had worse family functioning (PedsQL-Family Impact Module Total Score, P ≤ .012), greater parental stress (PIP-F Total Score, P ≤ .016; PIP-D Total Score, P ≤ .013), and poorer psychosocial functioning (Pediatric Symptom Checklist Total Score, P ≤ .003). There were no statistically significant between-group differences in physical functioning based on the functional Disability Inventory. CONCLUSION Fecal incontinence significantly decreases quality of life compared with functional constipation alone in children. Older children with functional constipation+fecal incontinence may be at particular risk. Strategies for early identification and treatment of constipation along with diagnosis and treatment of related adjustment difficulties may mitigate the negative impact of this highly prevalent condition.

Comorbid Conditions Do Not Differ in Children and Young Adults with Functional Disorders with or without Postural Tachycardia Syndrome.

OBJECTIVE To determine if several multisystem comorbid conditions occur more frequently in subjects with tilt-table defined postural tachycardia syndrome (POTS) compared with those without. STUDY DESIGN Retrospective chart review of 67 subjects aged 6-24 years, referred to a tertiary care neurogastroenterology and autonomic disorders clinic for a constellation of functional gastrointestinal, chronic pain, and autonomic complaints. All patients underwent formal autonomic testing, Beighton scores assessment for joint hypermobility (0-9), and fibromyalgia tender points (0-18) (43 subjects). RESULTS Twenty-five subjects (37%) met tilt table criteria for POTS. The median age of 16 years (range, 12-24 years) in the POTS group differed from 15 years (range, 6-21 years) in the no-POTS group (P = .03). Comorbidities including chronic fatigue, sleep disturbances, dizziness, syncope, migraines, functional gastrointestinal disorders, chronic nausea, fibromyalgia, and joint hypermobility did not differ between groups. All subjects with fibromyalgia by tender point-examination had a Beighton score ≥ 4 (P = .002). CONCLUSIONS Comorbid conditions are equally prevalent in children and young adults with and without tilt-table defined POTS, suggesting that POTS itself is not a cause of the other comorbidities. Instead, POTS likely reflects another comorbid condition in children with functional disorders. Dizziness and syncope, classically associated with POTS, are not predictive of a diagnosis of POTS by tilt table, a test that is still required for formal diagnosis. These results suggest a paradigm shift in the concept of POTS as the physiological basis of many functional symptoms.

Neurostimulation for abdominal pain-related functional gastrointestinal disorders in adolescents: a randomised, double-blind, sham-controlled trial

BACKGROUND Development of safe and effective therapies for paediatric abdominal pain-related functional gastrointestinal disorders is needed. A non-invasive, US Food and Drug Administration-cleared device (Neuro-Stim, Innovative Health Solutions, IN, USA) delivers percutaneous electrical nerve field stimulation (PENFS) in the external ear to modulate central pain pathways. In this study, we evaluated the efficacy of PENFS in adolescents with abdominal pain-related functional gastrointestinal disorders. METHODS In this randomised, sham-controlled trial, we enrolled adolescents (aged 11-18 years) who met Rome III criteria for abdominal pain-related functional gastrointestinal disorders from a single US outpatient gastroenterology clinic. Patients were randomly assigned (1:1) with a computer-generated randomisation scheme to active treatment or sham (no electrical charge) for 4 weeks. Patients were stratified by sex and presence or absence of nausea. Allocation was concealed from participants, caregivers, and the research team. The primary efficacy endpoint was change in abdominal pain scores. We measured improvement in worst abdominal pain and composite pain score using the Pain Frequency-Severity-Duration (PFSD) scale. Participants with less than 1 week of data and those with organic disease identified after enrolment were excluded from the modified intention-to-treat population. This trial has been completed and is registered with ClinicalTrials.gov, number NCT02367729. FINDINGS Between June 18, 2015, and Nov 17, 2016, 115 children with abdominal pain-related functional gastrointestinal disorders were enrolled and assigned to either PENFS (n=60) with an active device or sham (n=55). After exclusion of patients who discontinued treatment (n=1 in the PENFS group; n=7 in the sham group) and those who were excluded after randomisation because they had organic disease (n=2 in the PENFS group; n=1 in the sham group), 57 patients in the PENFS group and 47 patients in the sham group were included in the primary analysis. Patients in the PENFS group had greater reduction in worst pain compared with sham after 3 weeks of treatment (PENFS: median score 5·0 [IQR 4·0-7·0]; sham: 7·0 [5·0-9·0]; least square means estimate of change in worse pain 2·15 [95% CI 1·37-2·93], p<0·0001). Effects were sustained for an extended period (median follow-up 9·2 weeks [IQR 6·4-13·4]) in the PENFS group: median 8·0 (IQR 7·0-9·0) at baseline to 6·0 (5·0-8·0) at follow-up versus sham: 7·5 (6·0-9·0) at baseline to 7·0 (5·0-8·0) at follow-up (p<0·0001). Median PFSD composite scores also decreased significantly in the PENFS group (from 24·5 [IQR 16·8-33.3] to 8·4 [3·2-16·2]) compared with sham (from 22·8 [IQR 8·4-38·2] to 15·2 [4·4-36·8]) with a mean decrease of 11·48 (95% CI 6·63-16·32; p<0·0001) after 3 weeks. These effects were sustained at extended follow-up in the PENFS group: median 24·5 (IQR 16·8-33·3) at baseline to 12 (3·6-22·5) at follow-up, compared with sham: 22·8 (8·4-38·2) at baseline to 16·8 (4·8-33·6) at follow-up (p=0·018). Ten patients reported side-effects (three of whom discontinued the study): ear discomfort (n=6; three in the PENFS group, three in the sham group), adhesive allergy (n=3; one in the PENFS group, two in the sham group), and syncope due to needle phobia (n=1; in the sham group). There were no serious adverse events. INTERPRETATION Our results show that PENFS with Neuro-Stim has sustained efficacy for abdominal pain-related functional gastrointestinal disorders in adolescents. This safe and effective approach expands treatment options and should be considered as a non-pharmacological alternative for these disorders. FUNDING American Neurogastroenterology and Motility Society.

Childhood Chronic Nausea: Is It Just a Queasy Stomach?

Chronic nausea is an increasingly acknowledged complaint in children. It is commonly encountered in association with functional gastrointestinal (GI) disorders but can also occur in isolation. As such, there is no pediatric diagnostic classification for chronic idiopathic nausea. The pathophysiology appears complex, from foregut motor and sensory disturbances to autonomic imbalance and CNS influences. Also, there is scarcity of specific treatments that target this highly bothersome symptom. Treatment is mainly empiric or aimed at other functional complaints. Our retrospective data indicate a high prevalence of comorbid conditions in children with chronic nausea. These include migraines, autonomic disturbances, sleep problems, fatigue, and anxiety. Identifying specific features and targeting these therapeutically may be essential for improved treatment outcomes.

High Prevalence of Nausea among School Children in Latin America.

OBJECTIVES To evaluate the prevalence of nausea and its association with functional gastrointestinal disorders (FGIDs) in a large-scale, population-based study of Latin American school children. STUDY DESIGN This cross-sectional study collected data from children in 3 Latin American countries. A Spanish version of the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III Version (QPGS-III) was administered to school children in Central and South America. Subjects were classified into FGIDs based on Rome criteria (QPGS-III). Students from 4 public and 4 private schools in the countries of El Salvador, Panama, and Ecuador participated in this epidemiologic study. RESULTS A total of 1137 school children with mean age 11.5 (SD 1.9, range 8-15) years completed the QPGS-III (El Salvador n = 399; Panama n = 321; Ecuador n = 417). Nausea was present in 15.9% of all school children. Two hundred sixty-eight (24%) children met criteria for at least 1 FGID. Nausea was significantly more common in children with FGIDs compared with those without: El Salvador 38% vs 15% (P < .001); Panama 22% vs 7% (P < .001); Ecuador 25% vs 13% (P = .004). Among children with FGIDs, those with functional constipation had a high prevalence of nausea. Nausea was significantly more common in girls and children attending private schools. CONCLUSIONS Nausea is commonly present in Latin American school children. FGIDs are frequently associated with nausea.

Methodologic considerations for studies of chronic nausea and vomiting in adults and children

Methods to characterize and quantify severity of chronic nausea and vomiting and to elucidate their underlying mechanisms have received significant attention for both adult and pediatric patients. Validated dyspepsia symptom surveys include measures of nausea and vomiting intensity in relation to other upper gut symptoms. Visual analog scales quantify nausea intensity in real-time in physiologic studies and have been employed as enrollment criteria in clinical trial settings. A new nausea and vomiting survey has been administered to gastroparesis patients to provide insight into timing, triggers, and autonomic and psychological correlates of these symptoms. Several gastric sensorimotor and extragastric abnormalities are proposed to contribute to nausea and vomiting pathogenesis, but their relations to symptom severity are either limited or uninvestigated. Gastric emptying delays are prevalent in patients with chronic nausea and vomiting, as are blunting of fundic accommodation, aberrant gastric slow wave rhythms, and heightened perception of noxious and physiologic luminal stimulation. Potential extragastric correlates of nausea and vomiting include transit delays distal to the stomach, autonomic abnormalities, altered central nervous system activation, metabolic dysregulation, and psychological dysfunction. One goal of novel survey development will be to relate these physiologic correlates to specific symptom presentations to gain insight into mechanisms of nausea in different clinical conditions. Pediatric patients represent special challenges because of the different disorders that cause nausea and vomiting in children and differences in understanding disease manifestations, the ability to communicate symptom intensity and characteristics, and immature coping mechanisms compared to adults.

Current concepts in functional gastrointestinal disorders.

Purpose of review Functional gastrointestinal disorders (FGIDs) are some of the most common and challenging disorders in pediatrics. Recurrent abdominal pain is the central feature of pain-associated FGIDs such as irritable bowel syndrome. A thorough understanding of current pathophysiological concepts is essential to successful management. Recent findings The brain–gut axis, role of microbiota and the biopsychosocial model are emerging concepts in FGIDs. The biopsychosocial model focuses on the interplay between genes, environment, and physical and psychosocial factors. Interactions between microbiota and the central, enteric and autonomic nervous systems form the link between gut functions and conscious perceptions. Irritable bowel syndrome is the most extensively studied and prototypical pain-associated FGIDs. An aberrant processing of pain or physiologic signals originating from the gut causes a state of visceral hypersensitivity – a central mechanism of functional pain. Psychosocial and autonomic influences also play large roles. Therapy is tailored to the individual patient and comorbid symptoms. Summary This review highlights the complex mechanisms and the aberrant brain–gut neural connections forming the basis of FGIDs. Successful management of FGIDs requires knowledge of the underlying pathophysiology coupled with a multidisciplinary treatment approach. Management should focus on cognitive behavioral therapy, dietary factors along with gastrointestinal motility and psychotropic drug therapy.

Functional Nausea in Children.

ABSTRACT Chronic nausea is a highly prevalent, bothersome, and difficult-to-treat symptom among adolescents. When chronic nausea presents as the predominant symptom and is not associated with any underlying disease, it may be considered a functional gastrointestinal disorder and named “functional nausea.” The clinical features of functional nausea and its association with comorbid conditions provide clues to the underlying pathophysiological mechanisms. These may include gastrointestinal motor and sensory disturbances, autonomic imbalance, altered central nervous system pathways, or a combination of these. This review summarizes the current knowledge on mechanisms and treatment strategies for chronic, functional nausea in children.

Chronic idiopathic nausea.

Chronic nausea is a prevalent but poorly described symptom in adolescents. It often co-occurs with other functional gastrointestinal disorders (FGIDs) but may also present in isolation. A multitude of triggers and complex neural pathways underlie the sensation of nausea. These include gastrointestinal and blood-borne insults, dysmotility, vestibular or central nervous system pathways, an aberrant autonomic nervous system, and psychosocial factors. Although clinical algorithms are lacking, diagnosis is typically made on the basis of a thorough clinical history and without extensive testing. Treatment is mainly empiric and may be directed at comorbid symptoms such as migraine, delayed gastric emptying, orthostatic intolerance, and visceral hypersensitivity. Chronic idiopathic nausea is an increasingly prevalent symptom that needs careful clinical assessment and individualized treatment plans.