Childhood Functional Gastrointestinal Disorders: Neonate/Toddler

In 2006, a consensus concerning functional gastrointestinal intestinal disorders in infants and toddlers was described. At that time, little evidence regarding epidemiology, pathophysiology, diagnostic workup, treatment strategies, and follow-up was available. Consequently, the criteria for the clinical entities were more experience based than evidence based. In the past decade, new insights have been gained about the different functional gastrointestinal intestinal disorders 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 can impact the pain experience. In 2006, a consensus concerning functional gastrointestinal intestinal disorders in infants and toddlers was described. At that time, little evidence regarding epidemiology, pathophysiology, diagnostic workup, treatment strategies, and follow-up was available. Consequently, the criteria for the clinical entities were more experience based than evidence based. In the past decade, new insights have been gained about the different functional gastrointestinal intestinal disorders 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 can impact the pain experience. Infant and toddler functional gastrointestinal disorders (FGIDs) include a variable combination of often age-dependent, chronic, or recurrent symptoms not explained by structural or biochemical abnormalities. Functional symptoms during childhood sometimes accompany normal development (eg, infant regurgitation), or they can arise from maladaptive behavioral responses to internal or external stimuli (eg, retention of feces in the rectum often results from an experience with painful defecation). The clinical expression of an FGID varies with age, and depends on an individual’s stage of development, particularly with regard to physiologic, autonomic, affective, and intellectual development. As the child gains the verbal skills necessary to report pain, it is then possible to diagnose pain-predominant FGIDs. Through the first years, children cannot accurately report symptoms such as nausea or pain. The infant and preschool child cannot discriminate between emotional and physical distress. Therefore, clinicians depend on the reports and interpretations of the parents, who know their child best, and the observations of the clinician, who is trained to differentiate between health and illness. The decision to seek medical care for symptoms arises from a caretaker’s concern for the child. The threshold for concern varies with previous experiences and expectations, coping style, and perception of illness. For this reason, the office visit is not only about the child’s symptom, but also about the family’s fears. The clinician must not only make a diagnosis, but also recognize the impact of the symptom on the family’s emotions and ability to function. Therefore, any intervention plan must attend to both the child and the family. Effective management depends on securing a therapeutic alliance with the parents. Childhood FGIDs are not dangerous when the symptoms and caregiver’s concerns are addressed and contained. Conversely, failed diagnosis and inappropriate treatments of functional symptoms may be the cause of needless physical and emotional suffering. Disability from a functional symptom is related to maladaptive coping with the symptom. In severe cases, well-meaning clinicians inadvertently co-create unnecessarily complex and costly solutions, as well as ongoing emotional stress that promotes disability.1Scherer L.D. Zikmund-Fisher B.J. Fagerlin A. et al.Influence of “GERD” label on parents' decision to medicate infants.Pediatrics. 2013; 131: 839-845Crossref Scopus (55) Google Scholar This article provides a description, assessment, and analysis of each FGID that affects the neonate/toddler age group (Table 1). Figure 1 shows the age of presentation of FGIDs in the pediatric age group, and Table 2 shows a summary of the prevalence of FGIDs in this age group, as well as their pathophysiology and treatment. We will then review the developmental neurobiology of the pain response, as well as the assessment of pain in infants and toddlers.Table 1G. Functional Gastrointestinal Disorders in Neonates and ToddlersG1. Infant regurgitationG2. Infant rumination syndromeG3. Cyclic vomiting syndromeG4. Infant colicG5. Functional diarrheaG6. Infant dyscheziaG7. Functional constipation Open table in a new tab Table 2Prevalence, Pathophysiology, and Treatment of Functional Gastrointestinal Disorders in Neonates and ToddlersDisorderAgePrevalence, %PathophysiologyTreatmentOutcomeInfant regurgitation3 wk to 12 mo41−67 (peak at 4 mo of age)Small esophageal volume, overfeeding, infant positioningEducation, smaller feedings feeding thickening, positioningResolves in 90% by 12 mo of ageInfant rumination syndrome3−8 mo1.9Emotional and sensory deprivationBehavioral interventions, improved nurturingRecovery with nurturingCyclic vomiting syndromeWide range3.4Activation of the emetic reflex and the HPA axisPrevention of triggers, prophylactic medications, abortive medications, supportive measuresUsually resolves as child gets older but may continue or change to abdominal migraine or migraine headacheInfant colicEarly infancy to 5 mo5−19Results from normal developmental processNormal variations in development and temperament account for differences in cryingInfluence of parental perceptionsReassuranceNo evidence that pharmacologic interventions are usefulThere is inadequate evidence whether elimination of cow’s milk protein, probiotics, or herbal interventions provide viable and effective treatmentsThese approaches remain problematic and controversialResolves by 5 mo of ageFunctional diarrhea6−60 mo6−7Dietary and motility abnormalities; increased mucosal secretion?Education, dietary changesUsually resolves by 60 mo of ageInfant dyscheziaBirth to 9 mo2.4Uncoordinated defecation dynamicsEducation and reassurance, avoidance of anal stimulations and laxativesResolves in most cases by 9 mo of ageFunctional constipationBirth to adulthood3−27Results from painful defecation associated with withholdingEducation, behavioral interventions, laxativesSuccessful long-term treatment in 80% after first year, and increases over timeHPA, hypothalamic−pituitary−adrenal. Open table in a new tab HPA, hypothalamic−pituitary−adrenal. Reflux refers to retrograde involuntary movement of gastric contents in and out of the stomach, and is often referred as gastroesophageal reflux.2Vandenplas Y. Rudolph C.D. Di Lorenzo C. et al.Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).J Pediatr Gastroenterol Nutr. 2009; 49: 498-547Crossref PubMed Scopus (58) Google Scholar When the reflux is high enough to be visualized it is called regurgitation. Regurgitation of stomach contents into the esophagus, mouth, and/or nose is common in infants and is within the expected range of behaviors in healthy infants. Infant regurgitation is the most common FGID in the first year of life.3Van Tilburg M.A. Hyman P.E. Rouster A. et al.Prevalence of functional gastrointestinal disorders in infants and toddlers.J Pediatr. 2015; 166: 684-689Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar Recognition of infant regurgitation avoids unnecessary doctor visits and unnecessary investigations and therapy for gastroesophageal reflux disease (GERD).2Vandenplas Y. Rudolph C.D. Di Lorenzo C. et al.Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).J Pediatr Gastroenterol Nutr. 2009; 49: 498-547Crossref PubMed Scopus (58) Google Scholar Infant regurgitation is distinguished from vomiting, which is defined by a central nervous system reflex involving both autonomic and skeletal muscles in which gastric contents are forcefully expelled through the mouth because of coordinated movements of the small bowel, stomach, esophagus, and diaphragm. Regurgitation is also different from rumination, in which previously swallowed food is returned to the pharynx and mouth, chewed, and swallowed again. When the regurgitation of gastric contents causes complications or contributes to tissue damage or inflammation (eg, esophagitis, obstructive apnea, reactive airway disease, pulmonary aspiration, feeding and swallowing difficulties, or failure to thrive), it is called GERD.2Vandenplas Y. Rudolph C.D. Di Lorenzo C. et al.Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).J Pediatr Gastroenterol Nutr. 2009; 49: 498-547Crossref PubMed Scopus (58) Google ScholarG1. Diagnostic Criteria for Infant RegurgitationMust include both of the following in otherwise healthy infants 3 weeks to 12 months of age:1.Regurgitation 2 or more times per day for 3 or more weeks2.No retching, hematemesis, aspiration, apnea, failure to thrive, feeding or swallowing difficulties, or abnormal posturing G1. Diagnostic Criteria for Infant Regurgitation Must include both of the following in otherwise healthy infants 3 weeks to 12 months of age:1.Regurgitation 2 or more times per day for 3 or more weeks2.No retching, hematemesis, aspiration, apnea, failure to thrive, feeding or swallowing difficulties, or abnormal posturing There are minor changes from Rome III. Recently, a position paper by the North American Society of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN) and the European Society of Pediatric Gastroenterology Hepatology and Nutrition added “bothersome symptoms” as one criterion to differentiate infant regurgitation from GERD.3Van Tilburg M.A. Hyman P.E. Rouster A. et al.Prevalence of functional gastrointestinal disorders in infants and toddlers.J Pediatr. 2015; 166: 684-689Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar The challenge with that definition is that quantitative methods to define “troublesome” are missing. Infants cannot communicate if they are bothered. Variations in clinician and parent interpretations of troublesome have resulted in unnecessary evaluation and treatment of many infants with regurgitation, not GERD. There is a lack of correlation between crying, irritability, and GER.4Orenstein S.R. Hassall E. Furmaga-Jablonska W. et al.Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease.J Pediatr. 2009; 154: 514-520 e4Abstract Full Text Full Text PDF PubMed Scopus (270) Google Scholar GER is not a common cause of unexplained crying, irritability, or distressed behavior in otherwise healthy infants.2Vandenplas Y. Rudolph C.D. Di Lorenzo C. et al.Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).J Pediatr Gastroenterol Nutr. 2009; 49: 498-547Crossref PubMed Scopus (58) Google Scholar Therefore, we have elected to leave “troublesome” symptoms out of the criteria. Daily regurgitation is more common in young infants than in older infants and children, and is found in higher rates in neonates.5Hegar B. Dewanti N.R. Kadim M. et al.Natural evolution of regurgitation in healthy infants.Acta Paediatr. 2009; 98: 1189-1193Crossref PubMed Scopus (118) Google Scholar A recent study of 1447 mothers throughout the United States showed a prevalence of infant regurgitation of 26% using Rome III criteria.3Van Tilburg M.A. Hyman P.E. Rouster A. et al.Prevalence of functional gastrointestinal disorders in infants and toddlers.J Pediatr. 2015; 166: 684-689Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar Regurgitation occurs more than once a day in 41%−67% of healthy 4-month-old infants.2Vandenplas Y. Rudolph C.D. Di Lorenzo C. et al.Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).J Pediatr Gastroenterol Nutr. 2009; 49: 498-547Crossref PubMed Scopus (58) Google Scholar, 6Nelson S.P. Chen E.H. Syniar G.M. et al.Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group.Arch Pediatr Adolesc Med. 1997; 151: 569-572Crossref PubMed Scopus (475) Google Scholar Although regurgitation can occur at any age, the peak is around 4 months of age, with tapering beginning at 6 months and then declining in frequency until 12−15 months.5Hegar B. Dewanti N.R. Kadim M. et al.Natural evolution of regurgitation in healthy infants.Acta Paediatr. 2009; 98: 1189-1193Crossref PubMed Scopus (118) Google Scholar History and physical examination may provide evidence of disease outside the GI tract, including metabolic, infectious, and neurologic conditions associated with vomiting. Prematurity, developmental delay, and congenital abnormalities of the oropharynx, chest, lungs, central nervous system, heart, or GI tract are considered risk factors for GERD.2Vandenplas Y. Rudolph C.D. Di Lorenzo C. et al.Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).J Pediatr Gastroenterol Nutr. 2009; 49: 498-547Crossref PubMed Scopus (58) Google Scholar Evidence of failure to thrive, hematemesis, occult blood in the stool, anemia, food refusal, and swallowing difficulties, should prompt an evaluation for GERD.2Vandenplas Y. Rudolph C.D. Di Lorenzo C. et al.Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).J Pediatr Gastroenterol Nutr. 2009; 49: 498-547Crossref PubMed Scopus (58) Google Scholar Assessment to exclude an upper GI anatomical abnormality, such as malrotation or a gastric outlet obstruction, should be done if regurgitation persists past the first year of life, if it started early in the neonatal period, or it is associated with bilious vomiting, dehydration, or other complications. The natural history of infant regurgitation is one of spontaneous improvement.6Nelson S.P. Chen E.H. Syniar G.M. et al.Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group.Arch Pediatr Adolesc Med. 1997; 151: 569-572Crossref PubMed Scopus (475) Google Scholar Therefore, treatment goals are to provide effective reassurance and symptom relief while avoiding complications. Improving the caregiver−child interaction is often aided by relieving the caregiver’s fears about the condition of the infant, identifying sources of physical and emotional distress, and making plans to eliminate them. Management does not require medical interventions. There are multiple randomized trials showing a lack of benefit to the use of proton pump inhibitors in infants with regurgitation or those suspected of having GERD, mostly based on regurgitation and bothersome symptoms.4Orenstein S.R. Hassall E. Furmaga-Jablonska W. et al.Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease.J Pediatr. 2009; 154: 514-520 e4Abstract Full Text Full Text PDF PubMed Scopus (270) Google Scholar, 7Rosen R. Gastroesophageal reflux in infants: more than just a phenomenon.JAMA Pediatr. 2014; 168: 83-89Crossref PubMed Scopus (25) Google Scholar In addition, proton pump inhibitor treatment can be associated with adverse effects, mainly respiratory and GI infections.7Rosen R. Gastroesophageal reflux in infants: more than just a phenomenon.JAMA Pediatr. 2014; 168: 83-89Crossref PubMed Scopus (25) Google Scholar Conservative measures include positioning after meals and thickened feedings. Thickened feedings and antiregurgitation formulas can decrease regurgitation in healthy infants.8Horvath A. Dziechciarz P. Szajewska H. The effect of thickened-feed interventions on gastroesophageal reflux in infants: systematic review and meta-analysis of randomized, controlled trials.Pediatrics. 2008; 122: e1268-e1277Crossref PubMed Scopus (121) Google Scholar, 9Vandenplas Y. Leluyer B. Cazaubiel M. et al.Double-blind comparative trial with 2 antiregurgitation formulae.J Pediatr Gastroenterol Nutr. 2013; 57: 389-393Crossref PubMed Scopus (33) Google Scholar While frequent smaller-volume feedings are sometimes recommended,2Vandenplas Y. Rudolph C.D. Di Lorenzo C. et al.Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).J Pediatr Gastroenterol Nutr. 2009; 49: 498-547Crossref PubMed Scopus (58) Google Scholar there is little direct evidence to support the efficacy of this approach. Postprandial left-sided and prone position reduces regurgitation.10van Wijk M.P. Benninga M.A. Davidson G.P. et al.Small volumes of feed can trigger transient lower esophageal sphincter relaxation and gastroesophageal reflux in the right lateral position in infants.J Pediatr. 2010; 156 (748 e1): 744-748Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar Sleeping in prone and lateral position can increase the risk of sudden infant death syndrome. Therefore, the American Academy of Pediatrics recommends sleeping in the supine position.11Moon R.Y. Task Force on Sudden Infant Death SyndromeSIDS and other sleep-related infant deaths: expansion of recommendations for a safe infant sleeping environment.Pediatrics. 2011; 128: 1030-1039Crossref PubMed Scopus (222) Google Scholar Rumination is the habitual regurgitation of stomach contents into the mouth for the purpose of self-stimulation.12Fleisher D.R. Infant rumination syndrome: report of a case and review of the literature.Am J Dis Child. 1979; 133: 266-269Crossref PubMed Scopus (41) Google Scholar Rumination has the following clinical presentations: infant rumination syndrome, rumination in neurologically impaired children and adults, and rumination in healthy older children and adults.12Fleisher D.R. Infant rumination syndrome: report of a case and review of the literature.Am J Dis Child. 1979; 133: 266-269Crossref PubMed Scopus (41) Google Scholar The latter 2 presentations are not discussed in this supplement.G2. Diagnostic Criteria for Rumination SyndromeMust include all of the following for at least 2 months:1.Repetitive contractions of the abdominal muscles, diaphragm, and tongue2.Effortless regurgitation of gastric contents, which are either expelled from the mouth or rechewed and reswallowed3.Three or more of the following:a.Onset between 3 and 8 monthsb.Does not respond to management for gastroesophageal reflux disease and regurgitationc.Unaccompanied by signs of distressd.Does not occur during sleep and when the infant is interacting with individuals in the environment G2. Diagnostic Criteria for Rumination Syndrome Must include all of the following for at least 2 months:1.Repetitive contractions of the abdominal muscles, diaphragm, and tongue2.Effortless regurgitation of gastric contents, which are either expelled from the mouth or rechewed and reswallowed3.Three or more of the following:a.Onset between 3 and 8 monthsb.Does not respond to management for gastroesophageal reflux disease and regurgitationc.Unaccompanied by signs of distressd.Does not occur during sleep and when the infant is interacting with individuals in the environment There have been no major changes from the Rome III criteria. However, given the difficulty for infants to communicate the presence of nausea, that word has been eliminated. The duration was also shortened to 2 months to be consistent with the rumination criteria for the older age groups. Infant rumination syndrome is rare, and has received little attention in the literature. A recent questionnaire based study of 1447 mothers showed a prevalence of 1.9%.3Van Tilburg M.A. Hyman P.E. Rouster A. et al.Prevalence of functional gastrointestinal disorders in infants and toddlers.J Pediatr. 2015; 166: 684-689Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar Rumination historically has been considered a self-stimulatory behavior that arises in the context of longstanding social deprivation. In the limited published literature, maternal behavior may appear to be neglectful or slavishly attentive, but there is no enjoyment in holding the baby or sensitivity to the infant’s needs for comfort and satisfaction.12Fleisher D.R. Infant rumination syndrome: report of a case and review of the literature.Am J Dis Child. 1979; 133: 266-269Crossref PubMed Scopus (41) Google Scholar Observing the ruminative act is essential for diagnosis. However, such observations require time, patience, and stealth because rumination can cease as soon as the infant notices the observer. No tests are necessary for the diagnosis of infant rumination syndrome. Historically, infant rumination syndrome responded to empathetic and responsive nurturing. Excessive and continuous loss of previously swallowed food may cause progressive malnutrition. Behavioral therapy is useful in eliminating rumination in highly motivated adults or children with neurologic impairment. There is no information on whether those techniques are useful in infant rumination syndrome. The most humane, developmentally appropriate, and comprehensive management aims at reversing the baby’s weight loss by eliminating its need for ruminative behavior. Treatment aims at helping the caregivers address their feelings toward the infant and to improve their ability to recognize and respond to the infant’s physical and emotional needs.13Bryant-Waugh R. Markham L. Kreipe R.E. et al.Feeding and eating disorders in childhood.Int J Eat Disord. 2010; 43: 98-111PubMed Google Scholar Although data on clinical course in infants and toddlers are sparse, epidemiologic studies clearly report that cyclic vomiting syndrome (CVS) can occur before 3 years of age.14Fitzpatrick E. Bourke B. Drumm B. et al.The incidence of cyclic vomiting syndrome in children: population-based study.Am J Gastroenterol. 2008; 103: 991-995Crossref PubMed Scopus (49) Google Scholar, 15Haghighat M. Rafie S.M. Dehghani S.M. et al.Cyclic vomiting syndrome in children: experience with 181 cases from southern Iran.World J Gastroenterol. 2007; 13: 1833-1836Crossref PubMed Scopus (55) Google Scholar A study from the United States found a prevalence of CVS of 0.2%−1.0% in children and of 3.4% in toddlers using the Rome III diagnostic criteria.3Van Tilburg M.A. Hyman P.E. Rouster A. et al.Prevalence of functional gastrointestinal disorders in infants and toddlers.J Pediatr. 2015; 166: 684-689Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar CVS occurs from infancy to midlife, and is most common between 2 and 7 years.16Fleisher D.R. Matar M. The cyclic vomiting syndrome: a report of 71 cases and literature review.J Pediatr Gastroenterol Nutr. 1993; 17: 361-369Crossref PubMed Scopus (148) Google Scholar In a study in Ireland reporting 41 cases, the median age at onset of symptoms was 4 years, with 46% of affected children having an onset of symptoms at the age of 3 years or younger.14Fitzpatrick E. Bourke B. Drumm B. et al.The incidence of cyclic vomiting syndrome in children: population-based study.Am J Gastroenterol. 2008; 103: 991-995Crossref PubMed Scopus (49) Google Scholar The poor recognition of the disorder leads to a timespan between the onset of symptoms and the diagnosis ranging between 1.1 to 3.4 years.14Fitzpatrick E. Bourke B. Drumm B. et al.The incidence of cyclic vomiting syndrome in children: population-based study.Am J Gastroenterol. 2008; 103: 991-995Crossref PubMed Scopus (49) Google ScholarG3. Diagnostic Criteria for Cyclic Vomiting SyndromeMust include all of the following:1.Two or more periods of unremitting paroxysmal vomiting with or without retching, lasting hours to days within a 6-month period2.Episodes are stereotypical in each patient3.Episodes are separated by weeks to months with return to baseline health between episodes of vomiting G3. Diagnostic Criteria for Cyclic Vomiting Syndrome Must include all of the following:1.Two or more periods of unremitting paroxysmal vomiting with or without retching, lasting hours to days within a 6-month period2.Episodes are stereotypical in each patient3.Episodes are separated by weeks to months with return to baseline health between episodes of vomiting The Rome IV committee reviewed the Rome III guidelines, NASPGHAN Cyclic Vomiting Syndrome Consensus Statement17Li B.U. Lefevre F. Chelimsky G.G. et al.North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition consensus statement on the diagnosis and management of cyclic vomiting syndrome.J Pediatr Gastroenterol Nutr. 2008; 47: 379-393Crossref PubMed Scopus (179) Google Scholar and International Headache Society18Headache Classification Committee of the International Headache SocietyThe International Classification of Headache Disorders, 3rd edition (beta version).Cephalalgia. 2013; 33: 629-808Crossref PubMed Scopus (5794) Google Scholar criteria for CVS and the validation and epidemiologic data derived from their utilization. We found no studies designed for the validation of the CVS guidelines after the publication of the NASPGHAN and International Headache Society guidelines. Those guidelines require a minimum of 5 attacks of intense nausea and vomiting in any interval for a child to be considered to have a diagnosis of CVS. The NASPGHAN consensus statement considered the Rome III minimum of 2 recurrent episodes for a child to be diagnosed with CVS as lacking specificity. However, 5 recent studies using Rome III criteria conducted in infants, toddlers, children, and adolescents failed to report a significantly higher prevalence of CVS than reported previously, as would be expected if the lack of specificity was important.19Saps M. Adams P. Bonilla S. et al.Parental report of abdominal pain and abdominal pain-related functional gastrointestinal disorders from a community survey.J Pediatr Gastroenterol Nutr. 2012; 55: 707-710Crossref PubMed Scopus (43) Google Scholar, 20Saps M. Nichols-Vinueza D.X. Rosen J.M. et al.Prevalence of functional gastrointestinal disorders in Colombian school children.J Pediatr. 2014; 164: 542-545.e1Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar, 21Devanarayana N.M. Adhikari C. Pannala W. et al.Prevalence of functional gastrointestinal diseases in a cohort of Sri Lankan adolescents: comparison between Rome II and Rome III criteria.J Trop Pediatr. 2011; 57: 34-39Crossref PubMed Scopus (98) Google Scholar, 22Van Tilburg M.A.L. Walker L. Palsson O. et al.Prevalence of child/adolescent functional gastrointestinal disorders in a national US community sample.Gastroenterology. 2014; 146: S143-S144Google Scholar The consistency of the epidemiologic data using the Rome III criteria and the narrow range of prevalence of CVS found in 4 studies (range, 0.2%−3.4%) using the Rome III criteria stands in contrast with the lack of epidemiologic data using the NASPGHAN criteria or the International Headache Society criteria. The committee agreed that, based on the important impact for the child’s quality of life and family disruption derived from each CVS attack, early diagnosis is important. Therefore, the committee maintained 2 as the minimum number of episodes required. Given the difficulty for infants to communicate the presence of nausea, that word has been eliminated from the criteria. CVS is characterized by stereotypical and repeated episodes of vomiting lasting from hours to days with intervening periods of return to baseline health.17Li B.U. Lefevre F. Chelimsky G.G. et al.North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition consensus statement on the diagnosis and management of cyclic vomiting syndrome.J Pediatr Gast