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Functional Gastrointestinal Disorders: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition

2002; Lippincott Williams & Wilkins; Volume: 35; Linguagem: Inglês

10.1097/00005176-200208002-00008

1536-4801

Jeffrey S. Hyams, Richard B. Colletti, Christophe Fauré, Elizabeth Gabriel‐Martinez, H. V. L. Maffei, Mauro Batista de Morais, Quak Seng Hock, Yvan Vandenplas,

Health, psychology, and well-being

SUMMARY OF THE PROBLEM Functional gastrointestinal disorders are defined as conditions in which a variable combination of chronic or recurrent gastrointestinal symptoms are present in the absence of known structural or biochemical abnormalities. There is no apparent organic disease or objective evidence of a pathologic condition. In clinical practice, most children with chronic gastrointestinal complaints have functional disorders. Despite their common occurrence, we know very little about the pathophysiology of most of these conditions. A diagnosis of a functional disorder is largely based on a patient's report of symptoms. Whereas adults can offer accurate histories, this is not necessarily the case in children, especially those who are young. Moreover, parents often play a large role in reporting their child's symptoms as well as in making the decision about whether to seek health care. Often the child–parent unit must be evaluated when addressing functional disorders. Considerable effort has been spent in defining pediatric functional gastrointestinal disorders. A multinational team of senior clinicians suggested working definitions (1). A recent monograph has described the spectrum of these disorders (2). It has been observed that some pediatric functional gastrointestinal disorders accompany normal development (e.g., infant regurgitation), or may be triggered by behavioral responses to age-appropriate activities (functional fecal retention during toilet training). It was also suggested that some children could inherit a temperament characterized by a predilection to gastrointestinal reactivity to stress, thereby constituting a genetic susceptibility to functional gastrointestinal disorders. At the same time it is recognized that environmental factors (parental health care seeking, stress, culture, geographic location) might play a role in the pathogenesis of functional gastrointestinal disorders. In the biopsychosocial model of clinical practice, symptoms represent the end result of autonomic nervous system reactivity and recovery, environmental stressors, and the child's ability to cope. They are also influenced by parental responses and coping. In this report, we address functional gastrointestinal disorders associated with vomiting, abdominal pain, and disordered defecation. We have not considered infant regurgitation, which is discussed in another Working Group report. CYCLIC VOMITING SYNDROME I. Summary of the Problem The cyclic vomiting syndrome (CVS) is characterized by recurrent, severe, discrete episodes of acute nausea and vomiting lasting from hours to days, with intervals of baseline normal function lasting weeks to months between episodes (3,4). Age of onset is quite variable, with most children between 6 and 10 years of age at the start of symptoms. Younger and older children also can be affected. There is no apparent metabolic, gastrointestinal, central nervous system, biochemical, or other disease causing vomiting. The frequency of episodes averages 12 per year (range, 1–70), and intervals between attacks may be regular or sporadic. Episodes tend to begin at the same time of the day, predominantly during the night or early morning. The duration of episodes tends to be similar in individual patients. Samuel Gee published the original description of cyclic vomiting syndrome in the 1880s. Although the cause and pathogenesis are unknown, cyclic vomiting syndrome appears to be related to migraine headache and abdominal migraine in that it is a paroxysmal disorder of brain–gut interaction. Currently, treatment consists of antiemetic medications for relief of nausea and vomiting, as well as prophylaxis with medications used to prevent recurrent migraine. In most children, the disorder is self-limited or resolves before adulthood. However, the episodes of vomiting are intense and disabling, often require parenteral medications and hospitalization, and leave the patient and family feeling distraught and helpless. Patients may be prevented from attending school or holding a job. Fluid and electrolyte disturbances, Mallory-Weiss tears, and inappropriate secretion of antidiuretic hormone can complicate episodes. Recurrent vomiting can lead to chronic esophagitis and erosion of dental enamel. II. Major Issues Requiring Investigation and Implementation The cause and pathogenesis of CVS need to be determined. Although in many patients CVS appears to be associated with migraine, in a significant portion it does not. There is no objective marker for migraine, and the criteria for the diagnosis of migraine-associated CVS have not been validated. It has not been established that migraine-associated CVS has a different cause than non–migraine-associated CVS. To determine whether there is a causative link with migraine, it is necessary to perform prospective studies, with standardized information-gathering tools, systematic testing, established criteria, and collaboration between pediatric neurologists as well as pediatric gastroenterologists There is an urgent need to improve the efficacy of treatment and prophylaxis of CVS. Treatment of acute episodes has included ondansetron, lorazepam, chlorpromazine, and droperidol. Prophylactic therapy has included amitriptyline, cyproheptadine, propranolol, sumatriptan, erythromycin, anticonvulsants, dietary measures, and psychotherapy. No randomized controlled trials have been performed to establish the efficacy of any therapy. III. Proposed Plan to Achieve Goals Randomized double blind placebo-controlled trials of the most promising medications are needed for both migraine-associated and non–migraine-associated groups. Both antiemetic and prophylactic medications should be studied. Multicenter studies may be necessary to enroll an adequate number of patients. Studies should be performed on several continents to determine whether differences in cause and response to therapy exist in various locales. A task force composed of pediatric gastroenterologists, neurologists, physiologists, and behavioral specialists should be formed to develop a multicenter database to systematically examine CVS, determine whether subtypes exist, and longitudinally follow a large cohort of patients. FUNCTIONAL DISORDERS ASSOCIATED WITH ABDOMINAL PAIN I. Summary of the Problem Almost four decades ago, Apley and co-workers defined recurrent abdominal pain as 3 or more bouts of pain, severe enough to affect activities, occurring over a period of not less than 3 months (5). Apley suggested that most children with this problem were suffering from pain associated with psychological difficulties. We now know that recurrent abdominal pain is a description and not a diagnosis. Moreover, the constraint of 3 months' duration is not regarded as relevant by all clinicians. Since Apley's work we have come to appreciate a long list of organic diseases associated with recurrent abdominal pain as well as the spectrum of functional gastrointestinal disorders. Pain has a nociceptive and an affective component, so that we recognize that many children have intolerance for mild discomfort, but others may cope better with pain, and not necessarily interrupt activities. The pain may be intermittent or continuous. Only a minority of cases of recurrent abdominal pain in childhood and adolescence are caused by organic disease. In most cases there is no demonstrable structural or biochemical abnormality. In studies from North America and Scandinavia, recurrent abdominal pain may affect 10% to 30% of children and adolescents. Approximately 5% to 15% of middle school and high school students have symptoms consistent with irritable bowel syndrome. The prevalence of functional dyspepsia in the general pediatric population is unknown, but approximately 5% of middle and high school students note dyspeptic symptoms. There are no epidemiologic data from other parts of the world. There are characteristic symptom patterns that appear to correlate with different clinical disorders. A recent publication proposed definitions for subtypes of recurrent abdominal pain in children (1). These definitions, presented here, may be helpful for both research and clinical care. Although the definitions imply sharply defined differences, some patients have features of more than one subtype. For example, a patient may have symptoms of both irritable bowel syndrome and functional dyspepsia, although often one symptom complex is predominant. Because the definition of a functional condition depends on the patient's report of symptoms, diagnosis in very young children depends on the caretaker's history. Whereas functional abdominal pain may occur in infancy, for this discussion we will assume the child is mature enough to provide an accurate pain history, the duration of symptoms is at least 12 weeks, which need not be consecutive, and the problem has occurred within the preceding 12 months. Functional dyspepsia is defined as persistent or recurrent pain or discomfort centered in the upper abdomen (above the umbilicus) in the absence of evidence (including upper endoscopy) that organic disease is likely to explain the symptoms. In the past this condition was often referred to as non-ulcer dyspepsia, but that term has largely been abandoned. Based on the predominant symptom, subgroups of functional dyspepsia have been suggested. These include ulcer-like dyspepsia in which pain centered in the upper abdomen is the predominant symptom, and dysmotility-like dyspepsia which is characterized by an unpleasant or troublesome nonpainful sensation (discomfort) centered in the upper abdomen often associated with upper abdominal fullness, early satiety, bloating, or nausea. The potential relationship of chronic infection with Helicobacter pylori and functional dyspepsia remains an area of controversy. There is no evidence that dyspepsia is related to defecation. Irritable bowel syndrome (IBS) is defined as abdominal discomfort or pain that has at least two of the following three features: relieved with defecation, onset associated with a change in frequency of stool, onset associated with a change in form (appearance) of stool. In addition, there are no inflammatory, structural, or metabolic abnormalities to explain the symptoms. Functional abdominal pain is defined as continuous or nearly continuous abdominal pain in a school-aged child or adolescent with no or only occasional relation of the pain with physiologic events (e.g., eating, menses, or defecation), and usually some loss of daily functioning (6). The pain is not faked (e.g., malingering) and the patient has insufficient criteria for other functional gastrointestinal disorders or diseases that would explain the abdominal pain. In some patients with functional abdominal pain, the symptom is intermittent rather than continuous. Abdominal migraine is defined as three or more paroxysmal episodes of intense, acute midline abdominal pain lasting 2 hours to several days, with intervening symptom-free intervals lasting weeks to months, in the preceding 12 months (7). There is no evidence of metabolic, gastrointestinal, or central nervous system disease. In addition, there are at least two of the following features: headache during episodes, photophobia during episodes, family history of migraine, headache confined to one side only, or an aura or warning period consisting of either visual disturbances (blurred or restricted vision), sensory symptoms (numbness or tingling), or motor abnormalities (e.g., slurred speech, inability to speak, paralysis). The precise pathophysiology of IBS, functional dyspepsia, functional abdominal pain, and abdominal migraine is not known. It is thought that symptoms may arise from changes in the brain–gut axis, which links the central and enteric nervous systems (ENS) (8). The ENS controls motor and secretory functions of the gastrointestinal system. It is semiautonomous in that the parasympathetic and sympathetic nervous systems modify its actions. Neurotransmitters in the ENS include serotonin (5HT), acetylcholine, substance P, vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP). 5-HT receptors appear to participate in mucosal sensory processing within the gut. Clinical experience suggests that IBS and functional dyspepsia occasionally follow bouts of presumed gastrointestinal infection. Patients with inflammatory bowel disease may manifest IBS-like symptoms even when bowel inflammation is quiescent. This visceral hyperalgesia (or hypersensitivity) may result from alterations in gut wall sensory receptors, abnormal modulation of sensory transmissions in the peripheral or central nervous system, or changes in cortical perception of afferent signals. Primary hyperalgesia refers to afferent gut nociceptors becoming hypersensitive after repetitive painful stimuli (e.g., inflammation), so that they transmit a pain signal after stimuli that were formerly sub-threshold (hyperalgesia) or after stimuli that do not normally cause pain (allodynia). 5HT is thought to play a role in the generation of these nociceptive impulses. Secondary hyperalgesia refers to changes in the central nervous system at and above the synapses between sensory afferent neurons and spinal cord interneurons. The role of motility abnormalities in the pathogenesis of IBS, functional dyspepsia, or functional abdominal pain is not clear. Therapy may be offered at several levels, including reassurance, dietary manipulation, psychotherapy, and pharmacologic measures. There are limited controlled trials of different treatment modalities of IBS, functional dyspepsia, or functional abdominal pain in childhood and adolescence. One study demonstrated a beneficial effect of fiber supplementation in recurrent abdominal pain, and the other demonstrated the efficacy of cognitive and behavioral modification therapy. Current medications used for IBS include anti-cholinergics, tricyclic antidepressants, and selective serotonin re-uptake inhibitors (SSRI). The 5HT3 -receptor antagonist alosetron (Lotronex, Glaxo Wellcome) which showed efficacy in the treatment of IBS in adult females with diarrhea-predominant symptoms was recently withdrawn from the United States market because of concerns of ischemic colitis. Tegaserode, a partial 5HT4-agonist, is currently being considered for approval as a treatment for constipation-predominant IBS in adults. For functional dyspepsia, antacids, H2-receptor antagonists, proton pump inhibitors, cisapride, metoclopramide, and tricyclic antidepressants are used. Cisapride has been withdrawn from the United States market because of reported adverse cardiovascular side effects but will continue to be available in Canada, Latin America, and Europe. For abdominal migraine, therapy is similar to that used for migraine prophylaxis and may include propranolol, cyproheptadine, and amitriptyline. II. Major Issues in Need of Investigation or Implementation Criteria for irritable bowel syndrome and functional dyspepsia need to be validated in childhood. The prevalence of IBS and functional dyspepsia in different ethnic groups and in different locations around the world should be investigated. The pathogenesis of IBS, functional dyspepsia, and functional abdominal pain should be investigated using emerging techniques such as the barostat, brain imaging (positron emission tomography (PET), functional magnetic resonance imaging (MRI), and molecular investigation of brain–gut peptides. The relationship of IBS and functional dyspepsia to previous enteric infection (e.g., postinfectious IBS) and inflammatory bowel disease should be defined. The role of early childhood risk factors for IBS, functional dyspepsia, and functional abdominal pain, including infantile colic, allergy, depression, anxiety, somatization, abuse, and family history of functional gastrointestinal disorders, need to be clarified. This should include a study of whether a genetic component is important in these disorders. There is a need to develop drugs to modulate abnormalities in sensorimotor function of the enteric nervous system in functional disorders to relieve specific symptoms and to assess the proper role of these drugs in the treatment of children and adolescents. The role of antidepressants (tricyclics, selective serotonin reuptake inhibitors) in the treatment of functional gastrointestinal disorders associated with abdominal pain needs to be assessed. The educational, social, and economic consequences of functional gastrointestinal disorders such as school absenteeism, inability to concentrate on studies, inability to participate in age-appropriate activities, health-care seeking, and lost time from parental employment should be studied. The relationship between H. pylori infection and functional dyspepsia should be clearly defined. Standard and novel psychological interventions need to be evaluated in symptom management, particularly promotion of coping through behavior modification to determine whether these patients can be treated nonmedically. Comorbid psychological disorders are often associated with functional gastrointestinal disorders, and there is a need to improve understanding of psychosocial processes and interventions. III. Proposed Plan to Achieve Goals It is important to build on the previous work of the Rome committee and validate or modify working definitions for the functional gastrointestinal disorders associated with abdominal pain. Attempts should be made to better define the concept of visceral hypersensitivity in functional abdominal pain. Cooperative studies with gastrointestinal physiologists and neurogastroenterologists need to be completed in patients of different ages. Newly emerging medications for the treatment of functional gastrointestinal disorders need to be evaluated in multicenter, multinational trials. Cooperative studies with mental health professionals and developmental specialists need to be devised to systematically evaluate behavioral therapies in the treatment of functional abdominal pain. Primary care physicians must be educated about the relationship of the central and enteric nervous systems. Moreover, primary care physicians need to be taught the criteria for functional gastrointestinal disorders. DISORDERS OF DEFECATION I. Summary of Problem Constipation is a symptom defined by the occurrence of any of the following, independent of stool frequency: passage of hard, scybalous, pebble-like or cylindrical cracked stools; straining or painful defecation;, passage of large stools that may clog the toilet; or stool frequency less than 3 per week, unless the child is breast fed. At times chronic constipation (symptoms for at least 2 weeks) presents as recurrent abdominal pain, enuresis, nonstructural urinary tract infections, or fecal soiling. Children may complain of a feeling of incomplete elimination. Irritable bowel syndrome with constipation predominance and chronic constipation share many descriptive similarities. Chronic constipation usually has no underlying structural, endocrine, or metabolic disease and is termed functional or idiopathic. The cause of functional constipation is still largely unknown and is probably multifactorial. 5HT and 5-HT receptors may play a role. 5HT4 receptor agonists are being evaluated for efficacy for treatment of constipation. Fecal soiling is the involuntary passage of stool associated with constipation, due to rectal impaction, which leads to a transient, reported diminished sensory threshold at the rectum. Nonretentive fecal soiling is the repeated, inappropriate passage of stool into a place other than the toilet, in a child older than 4 years. Some clinicians believe it may be necessary to obtain an abdominal radiograph before occult fecal retention due to incomplete passage of stool can be detected. In the United States, encopresis is the term often used to describe soiling, whether secondary to overflow or not. Infant dyschezia is defined as prolonged (>10 minutes) straining and crying before successful passage of soft stools in an otherwise healthy infant younger than 6 months of age. Constipation has been reported to account for about 3% of primary care visits and 25% of referrals to pediatric gastroenterologists. The reported prevalence of pediatric constipation is 15% in Greece, 16% in Canada, and 17% to 37% in Brazil, with a prevalence of 25% before age 2 in the latter country. Some non–breast-fed infants have constipation despite appropriate fluid intake. As a group, infants on soy formula tend to have firmer stools than infants on cow milk–containing formulas or protein hydrolysate preparations. The early onset of symptoms (infancy) points to predisposing constitutional factors in some subjects. Breast milk, types of formula used, and the introduction of various solids can affect stooling patterns. It has been suggested that cow milk allergy can be associated with constipation in infants (9). Stool withholding may occur in different situations. In children with early-onset constipation (first year of life), painful defecation can result in stool withholding because of fear of painful defecation. This will further exacerbate constitutional or dietary factors, which may have resulted in constipation in the first place. In other children, withholding may occur at the time of toilet training or if the child is distracted from taking the time to defecate in the toilet when engaged in other activities. However, some believe this latter behavior simply represents avoidance activity. Withholding stool occurs in up to 25% of toddlers at the time of initiation of toilet training. In this situation, the withholding is a primary event in the pathogenesis of constipation. It has been proposed that a diet deficient in fiber is an important contributor to constipation in some children. Despite this, data about dietary fiber intake in children are scarce. Lower intake in constipated than in nonconstipated children has been documented in Brazil and in Greece, but its role as a precipitating factor has not been determined. Conversely, it has been documented for adults, but not for children, that dietary fiber, mainly the insoluble portion, is beneficial in treating constipation. Other conditions, such as intercurrent illness, drugs, and stressful events, may cause constipation. The treatment of chronic constipation is based on the following principles: 1) relief of impaction with either enemas, polyethylene glycol 3350 solution, consistent use of laxatives or mineral oil; 2) maintenance therapy to establish normal bowel habits and prevent relapses with osmotic agents or lubricants in decreasing dosages over time; and 3) education of the child and family. The chronic use of stimulant laxatives should be avoided. Controversy still surrounds the use of cisapride in the treatment of chronic constipation with variable efficacy in different studies. Small frequent doses of PEG 3350 solution are now being used in some centers for maintenance therapy. A diet with adequate fruits, vegetables, and whole grains is recommended to ensure adequate intake of fiber. Parental and children's education and cooperation are fundamental. This step helps the family to understand normal bowel habits and diet, so that constipation and its treatment are demystified. Behavior modification, with establishment of a regular toilet habit, is important, and a system of rewards and praises may be used. The impact of constipation can be considerable, because complications frequently engender a great emotional burden for the child and the family. When managed incorrectly, children may present with severe abdominal pain, distension, or vomiting, which can lead to surgical intervention. When soiling or enuresis supervenes, secondary psychological alterations ensue, leading to school absence or failure. II. Major Issues in Need of Investigation or Implementation Recent publications (10–12) showed that most knowledge on functional constipation is based on observational studies and expert opinion, which needs to now be confirmed by controlled studies. There is a need for more prevalence studies, in developed and also in developing countries, where the emphasis has been on diarrheal disease. Studies are needed on the role of dietary fiber (soluble and insoluble) in the prevention and treatment of constipation. Data are required on safe amounts and types of fiber in the diets of infants being weaned from breast milk. Comprehensive reference tables that indicate quantities of soluble and insoluble fiber in foods would facilitate clinical care as well as research. There is a need to define the relationship of cow milk allergy and intolerance to chronic constipation. The role of constitutional factors, including primary variations in GI hormones, neurotransmitters, neuromuscular structures, motility, and water and bile acid reabsorption, need to be delineated. Perpetuating factors need to be identified, besides retentive behavior and paradoxical contraction of the external anal sphincter, that may be helpful in designing interventions. Retentive posturing must be defined as a primary or secondary event in the pathogenesis of functional constipation. Case-control longitudinal studies of babies with dyschezia should be performed trying to define whether it is a symptom complex that predicts stooling difficulties later in life. The efficacy and role of novel prokinetic agents, such as prucalopride, in the treatment of constipation in children needs to be studied. The short-term and long-term efficacy of PEG-preparations in the treatment of constipation in children should be studied. III. Proposed Plan to Achieve Goals Epidemiologic studies need to be performed to assess the prevalence and impact of constipation in children. Studies need to be performed to examine the attitudes of parents and health care providers regarding the causes and impact of difficult defecation and various treatment modalities. Randomized controlled trials are required to evaluate the efficacy and safety of currently used and novel medications, including lubricants, osmotic agents, stimulants, polyethylene glycol, and prokinetic agents. Randomized controlled trials to evaluate the efficacy of dietary fiber and fiber supplementation in the prevention and treatment of constipation should be undertaken TODDLER DIARRHEA I. Summary of the Problem Toddler diarrhea, or chronic nonspecific diarrhea, affects children from 1 to 5 years of age. The affected children are healthy looking though they pass 3 to 4 stools per day. The stool frequency can be as many as 10 per day, and may contain mucus and undigested vegetable materials. The first stool in the morning is usually large in amount, formed or semi-formed. Most of the bowel movements occur in the earlier part of the day, and no stools are passed at night. The stools are often described as particularly foul smelling. The general condition of the affected children is good, without failure to thrive or faltering of growth. At times their weight may be affected by iatrogenic dietary measures. Abdominal pain may be present but is seldom a prominent feature. Often, toddler diarrhea is preceded by an episode of acute gastroenteritis or another viral infection. Some investigators believe that before the onset of diarrhea, many of the affected children had colic or constipation. Although toddler diarrhea is noted to be one of the commonest causes of chronic diarrhea in developed countries, the exact incidence in the general population is unknown. There is a paucity of epidemiologic studies of this seemingly common condition both in the developed and developing countries. Current understanding of the pathogenic mechanism is that intestinal motility is disturbed in children with toddler diarrhea at the time of diagnosis. Normally, duodenal migratory complexes result in propulsive activity in the fasting state and they disappear in response to a meal. In one study, these complexes were not interrupted after intraduodenal glucose installment. This may result in a shorter intestinal transit time when compared with normal controls. Nutritional factors are recognized as playing an important role in the pathogenesis of toddler diarrhea. Children with toddler diarrhea often consume low-fat or very high fluid intake with very high fluid osmolarity. Carbohydrate malabsorption, especially from apple juice (fructose and sorbitol), has been reported (13). Bile salt malabsorption has also been suggested as a cause. Although it is very likely that dietary habits (low-fat feeding, low-fiber feeding, fructose and sorbitol overconsumption) are part of the spectrum of factors favoring toddler's diarrhea, it is clear that the origin is often multifactorial. Indeed, although toddler's diarrhea may disappear in some children by increasing the fat content or by limiting juice consumption, many children remain asymptomatic despite consumption of far more juice than subjects who are symptomatic. General bowel habits, physical activity, intestinal transit time, intestinal microflora, consumption of probiotics, and stress also may be important in the pathogenesis of toddler's diarrhea. The first line of treatment is to identify obvious causes such as dietary abnormalities. For those with no obvious cause, treatment with loperamide and psyllium has been advocated by some. Others advocate no treatment at all. Though the diarrhea may be troublesome, the outcome is generally good. More than 90% are free of loose stools by 40 months of age. II. Major Issues in Needs of Investigation and Implementation Although toddler diarrhea is well recognized as one of the most common causes of prolonged diarrhea in infants and toddlers, the epidemiology remains obscure both in developed and developing countries. There is a lack of prevalence data in large populations. Such data are needed to assess the scale of the problem in the general population. The relationship of toddler diarrhea to ethnic groups, social cultural background, and educational status of the parents is unknown. The pathogenic mechanism of toddler diarrhea remains obscure. Is fruit juice consumption the primary cause of chronic nonspecific diarrhea? What is the role of dietary fiber? What is the role of probiotics? Probiotics have been used successfully in children with toddler's diarrhea. However, it is difficult to demonstrate an imbalance of the intestinal microflora as the origin of toddler's diarrhea. Moreover, one could also hypothesize that stools in toddler's diarrhea resemble stools during breastfeeding and thus could be related to an excess of lactobacilli. In Belgium, the yeast Saccharomyces boulardii is frequently used in toddler's diarrhea. Although there are no clinical data supporting this indication (meaning that this should be evaluated prospectively and randomized), the basis for this treatment is that the yeast stimulate an increased length of the villi, activity of the disaccharidases, intestinal immunoglobulin secretion, and improve glucose uptake. There is a need to further analyze the general behavior and character of the child with toddler's diarrhea and his/her environment, feeding habits, stool habits, gastrointestinal microflora, and gastrointestinal transit time. III. Proposed Plan to Achieve Goals Well-designed prospective large-scale studies should be performed to learn more about normal bowel habits in infants and children. It may well appear that there are many children in the control population that have similar stools and bowel habits to those with toddler's diarrhea. It is possible that epidemiologic studies will show a lower threshold to consult a physician about a given problem in families with an affected child. Multinational studies defining normal stool patterns in different parts of the world from infancy through childhood should be performed. Multicenter randomized, controlled, double-blinded trials of probiotics in the treatment of chronic nonspecific diarrhea should be undertaken. There is a need to investigate the natural history of chronic nonspecific diarrhea to determine whether children develop functional gastrointestinal disorders including irritable bowel syndrome later in life. Fruit juice composition could be modified by increasing glucose to similar fructose concentrations to improve carbohydrate and water absorption. AEROPHAGIA I. Summary of the Problem Aerophagia is the swallowing of excessive volumes of air and is part of the spectrum of functional digestive symptoms (14). The most common manifestation is abdominal distention. However, abdominal gaseous distention also develops as a consequence of gastrointestinal production of gas (such as in lactase deficiency) or as a consequence of difficulties in elimination. Aerophagia frequently causes burping, abdominal cramps, colic, and flatulence. The presence of large volumes of air in the intestine is called aeroenteria or meteorism. In aerophagia, abdominal distention occurs progressively during the day and is maximal in the evening. Severe aerophagia causes massive distension of the bowel, possibly leading to ileus, volvulus, and even intestinal necrosis. Patients with aerophagia that is the consequence of swallowed air boluses can be divided in two groups: in the first group, the aerophagia is secondary to severe neurologic or anatomic problems, such as tracheal and pharyngeal malformations. Patients with chronic obstructive respiratory disease, such as obstructive apnea, develop aerophagia because of increased respiratory efforts. The second group develops aerophagia as part of functional disease, such as when children talk too much during meals. Some children habitually swallow large amounts of air. Delayed gastric emptying may be associated with gastric distention even in the absence of pathologic aerophagia. The treatment of aerophagia is largely behavioral modification. Gum chewing, avoidance of carbonated beverages, and refraining from talking during eating can all be helpful. In the presence of habitual air swallowing, behavioral intervention is warranted. II. Major Issues Needing Investigation or Implementation Studies need to be performed to develop further data on the composition and transit of gastrointestinal gas in pediatric patients. There is a need to determine whether aerophagia is an underappreciated cause of recurrent abdominal pain in children, especially the type that occurs primarily later in the day The relationship of anxiety to aerophagia should be studied. III. Proposed Plan to Achieve Goals Simple and reliable investigation techniques should be developed to quantify the frequency and volumes of swallowed air. We need to investigate whether our assumptions concerning pathogenesis are correct. Techniques should be developed to allow documentation of air swallowing to patients and their families because it is frequently difficult to convince patients and their families that aerophagia is contributing to a clinical problem. Acknowledgment: The authors thank Drs. Vanessa Ameen, Douglas Levine, and Kenneth Mandel, who served as technical advisors, and Drs. Paul Hyman, Arlene Dover, and Andree Rasquin-Weber who served as consultants.