Nonpharmacologic Treatment of Functional Abdominal Pain ... · Abdominal pain–related functional...

Nonpharmacologic Treatment ofFunctional Abdominal Pain Disorders:A Systematic ReviewJuliette M.T.M. Rutten, MDa*, Judith J. Korterink, MDa*, Leonie M.A.J. Venmans, PhDb, Marc A. Benninga, MD, PhDa,Merit M. Tabbers, MD, PhDa

abstract BACKGROUND AND OBJECTIVE: Various nonpharmacologic treatments are available for pediatricabdominal pain–related functional gastrointestinal disorders (AP-FGIDs). Data on efficacy andsafety are scarce. The goal of this study was to summarize the evidence regardingnonpharmacologic interventions for pediatric AP-FGIDs: lifestyle interventions, dietaryinterventions, behavioral interventions, prebiotics and probiotics, and alternative medicine.

METHODS: Searches were conducted of the Medline and Cochrane Library databases. Systematicreviews and randomized controlled trials (RCTs) concerning nonpharmacologic therapies inchildren (aged 3–18 years) with AP-FGIDs were included, and data were extracted on participants,interventions, and outcomes. The quality of evidence was assessed by using the GRADE approach.

RESULTS: Twenty-four RCTs were found that included 1390 children. Significant improvement ofabdominal pain was reported after hypnotherapy compared with standard care/wait-listapproaches and after cognitive behavioral therapy compared with a variety of controltreatments/wait-list approaches. Written self-disclosure improved pain frequency at the6-month follow-up only. Compared with placebo, Lactobacillus rhamnosus GG (LGG) andVSL#3 were associated with significantly more treatment responders (LGG relative risk: 1.31[95% confidence interval: 1.08 to 1.59]; VSL#3: P , .05). Guar gum significantly improvedirritable bowel syndrome symptom frequency; however, no effect was found for other fibersupplements (relative risk: 1.17 [95% confidence interval: 0.75 to 1.81]) or a lactose-free diet.Functional disability was not significantly decreased after yoga compared with a wait-listapproach. No studies were found concerning lifestyle interventions; gluten-, histamine-, orcarbonic acid–free diets; fluid intake; or prebiotics. No serious adverse effects were reported.The quality of evidence was found to be very low to moderate.

CONCLUSIONS: Although high-quality studies are lacking, some evidence shows efficacy ofhypnotherapy, cognitive behavioral therapy, and probiotics (LGG and VSL#3) in pediatricAP-FGIDs. Data on fiber supplements are inconclusive.

aDepartment of Pediatric Gastroenterology and Nutrition, Emma’s Children’s Hospital, Academic Medical Center, Amsterdam, Netherlands; and bPediatric Association of the Netherlands,Utrecht, Netherlands

Drs Rutten and Korterink participated in the design of the study, judged the eligibility and validity of the studies, and drafted the initial manuscript; Dr Venmansparticipated in the design of the study, performed the literature search, and judged the eligibility and validity of the studies; Dr Benninga participated in the design ofthe study and critically reviewed and revised the manuscript; Dr Tabbers participated in the design of the study, performed the literature search, judged the eligibilityand validity of the studies, and critically reviewed the manuscript; and all authors approved the final manuscript as submitted.

*Drs Rutten and Korterink contributed equally.

www.pediatrics.org/cgi/doi/10.1542/peds.2014-2123

DOI: 10.1542/peds.2014-2123

Accepted for publication Nov 25, 2014

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Abdominal pain–related functionalgastrointestinal disorders (AP-FGIDs),diagnosed according to the Rome IIIcriteria, are defined as chronic orrecurrent abdominal pain, notexplained by underlying organicdisorders.1 AP-FGIDs affect ∼20% ofchildren worldwide and includefunctional dyspepsia, irritable bowelsyndrome (IBS), abdominal migraine,functional abdominal pain (FAP), andfunctional abdominal painsyndrome.1,2 AP-FGIDs havea significant impact on children andadolescents’ quality of life, dailyactivities, and school absenteeism andcan have long-term psychologicalimplications.3 Moreover, patients withAP-FGIDs are at risk for continuedsymptoms in adulthood, and the costsare substantial.4–6

Standard medical care consists ofreassurance, education, and dietaryadvice.7 Despite ongoing efforts toidentify causal and contributingfactors in AP-FGIDs, successfulmanagement is complicated by anincomplete pathophysiologicunderstanding of the disorders. Thebiopsychosocial model, based ona complex interplay of genetic,physiologic, and psychological factors,is conceptualizing the etiology ofFGIDs.

It is hypothesized that pediatricAP-FGIDs are strongly associated withstress and psychological disorderssuch as anxiety and depression,8

wherein the coping potentials ofchildren with AP-FGIDs are lowcompared with those of healthychildren.9 Therefore, interventionssuch as cognitive behavioral therapy(CBT), hypnotherapy (HT), and yogaaim to teach alternative responses tostress.10 Systematic reviews haveconcluded that CBT and HT offerbeneficial effects for children withAP-FGIDs.11,12

The role of food in FGIDs has beenrevisited recently in the adultliterature.13,14 Food may triggersymptoms in FGID patients whoalready have physiologic alterations,

subsequently making themsusceptible for hypersensitivity.13

However, recognizing which specificfood components trigger symptoms isdifficult and can lead to a profusion ofinvestigations and dietary therapies,largely based on expert opinion.14

Two previous systematic reviewsreported that fiber supplements areineffective in treating AP-FGIDs,whereas conclusions werecontradictory regardingprobiotics.15,16 Treatment of childrenwho have AP-FGIDs can bechallenging, especially because high-quality evidence for pharmacologicinterventions is lacking.17 Althoughseveral systematic reviewssummarizing differentnonpharmacologic interventionsexist,11,15,18 the present systematicreview provides an up-to-dateoverview regarding the efficacy andsafety of all nonpharmacologictreatments for pediatric AP-FGIDs.Such a comprehensive and recentoverview is warranted.

METHODS

Literature Search

The Cochrane Library and Medlinedatabases were searched forsystematic reviews and randomizedcontrolled trials (RCTs) frominception to October 2013. Searchterms used items related to pediatricAP-FGIDs and variousnonpharmacologic treatments. Toidentify additional studies, referencelists of reviews and included studieswere searched by hand. The fullsearch strategy and key words areavailable from the authors.

Study Inclusion

Two authors (L.M.A.J.V. and M.M.T.)independently assessed the eligibilityof all abstracts. In cases ofdisagreement, consensus was reachedthrough discussion. Inclusion criteriawere: (1) study was a systematicreview or RCT; (2) study populationcomprised children aged 3 to18 years; (3) diagnosis of recurrent

abdominal pain (RAP), FAPS, IBS,functional dyspepsia, or abdominalmigraine as defined by the authors;(4) interventions were lifestyle advicesuch as physical exercise, dietaryinterventions (fiber supplements;lactose-, gluten-, histamine-, andcarbonic acid–free diets; and fluidintake), behavioral interventions suchas HT and CBT, prebiotics andprobiotics, and alternative medicine(acupuncture, homeopathy,mind–body therapy, musculoskeletalmanipulations such as osteopathicand chiropractic manipulations, andspiritual therapies such as yoga); (5)the intervention was compared withplacebo, no treatment, any othernonpharmacologic treatment, ora pharmacologic agent; and (6)outcomes were abdominal painintensity and/or frequency, quality oflife, functional disability (eg, schoolabsence), and adverse effects.Exclusion criteria were: (1) treatmentarm with ,10 patients; and (2)language other than English.Potentially relevant studies andstudies in which the title and abstractprovided insufficient informationwere retrieved as full-text articles.

Quality Assessment and DataExtraction

Two authors (L.M.A.J.V. and M.M.T.)independently rated themethodologic quality of the includedstudies by using the Cochrane risk ofbias tool. For each outcome, qualityof evidence was assessed by using theGRADE approach and was categorizedas very low, low, moderate, orhigh.19–21

The same authors extracted data fromincluded studies by using structureddata extraction forms containingitems on participants, study setting,interventions, and outcomes.Disagreements were resolved throughconsensus or by a third reviewer(M.A.B.).

Data Analysis

Dichotomous outcomes wereanalyzed as odds ratios (ORs) or

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relative risk (RRs) along with 95%confidence intervals (CIs). Forcontinuous outcomes, the meandifferences (MDs) with 95% CIs werereported. Heterogeneity wasquantified by using x2 tests and theI2 statistic, which can be interpretedas the percentage of the totalvariation between studies that isattributable to heterogeneity ratherthan chance. A value of 0% indicatesno observed heterogeneity, whereaslarger values show increasingheterogeneity. If heterogeneity wasnot revealed, results of the fixed effectmodel are presented. If there wassubstantial heterogeneity (.50%),the random effect model was used.

RESULTS

A total of 568 potentially relevantarticles and abstracts were identified(Fig 1). After removal of duplicates(n = 316) and screening of abstracts(n = 210), 42 full-text articles wereassessed for eligibility. Twenty-ninearticles were excluded because of thefollowing: adult study population (n = 6),irrelevant outcome measures, such asimprovement in rectal sensitivity orgastrointestinal symptoms without

abdominal pain (n = 2), no systematicreview or RCT (n = 15), or inclusiononly of trials that were alreadyincluded by another systematicreview (n = 6). Thirteen articlesremained for analysis: 7 systematicreviews11,12,15,16,18,22,23 (including18 RCTs) and 6 RCTs.24–29 Twoincluded trials concerned follow-upstudies,26,30 which will be discussedby using their original studies.31,32

Two systematic reviews11,12 includedstudies with ,10 patients pertreatment arm, and these studieswere therefore excluded.33–35

Data of 1390 children aged 3 to18 years were included for analysis.Sample sizes ranged from 21 to 200,and follow-up varied from 2 weeks to5 years. Four trials investigated fibersupplements compared withplacebo,24,36–38 and 2 trials studieda lactose-free diet.39,40 Four trialsinvestigated probiotics,27,41–43 and3 trials compared HT versus standardcare or a wait-list.25,32,44 Seven studiescompared CBT with standard care,physiotherapy, fiber supplements,biofeedback, and/or parentalsupport.28,31,45–49 One trial comparedyoga with a wait-list,50 and 1 trialevaluated written self-disclosure(WSD) in addition to standard care.29

No studies were included on lifestyleadvice or prebiotics. A range ofdifferent outcomes were measured, andeven if the same outcome wasmeasured, different measurementinstruments were used. All trialsmeasured abdominal pain as theprimary or secondary outcome.

Nine studies reporteddisability or schoolabsenteeism.25,31,32,38,42,44,47,49,50

Four studies assessed quality oflife,25,28,29,44 and 8 studies assessedadverse effects.24,25,37,38,41–44 Dataof 3 studies were pooled to performa meta-analysis of the efficacy of fibersupplements,36–38 and 3 studieswere used to perform a meta-analysison probiotics.41–43 Table 1 presentsthe characteristics of the includedstudies.

Methodologic Quality

The overall quality of evidence wasvery low to moderate. TheSupplemental Appendix displays theGRADE evidence profiles.

Concealment of allocation wasunclear in 6 studies.36,44–46,48,49 Dueto the nature of HT, CBT, WSD, andyoga, blinding was not possiblefor the caregiver orpatient.25,28,29,31,32,44–50 Dropout wasconsiderable in 4 studies36,40,41,47

or vaguely described in 3others.31,46,50 Two studies excludedpatients due to poor compliance.40,41

The method of randomization wasunclear in 3 studies.27,31,50 Alfvén andLindstrom48 provided no informationon outcome blinding or treatmentduration. Six trials did not presentresults with absolute numbers andwere therefore not included in themeta-analysis.27,39,40,44,47,48 Analysesfor follow-up were uncontrolledfor baseline differences by Levy et al.31

Because participants were recruitedthrough physician referral and flyers,these patients were therefore seriouslymotivated, which can cause bias.

Dietary Interventions

No studies were included evaluatinggluten-, histamine-, and carbonicacid–free diets or fluid intake.

Fiber Supplements

Two systematic reviews15,16

including 3 RCTs36–38 and 1 RCT24

evaluated the efficacy of fibersupplements compared with placebofor RAP. A systematic review byHuertas-Ceballos et al15 included2 RCTs, involving 92 children aged3 to 15 years.36,37 Children receivedfiber supplements for 6 weeks. Noinformation was available regardingdaily fiber intake before and/orduring intervention weeks.Information about abdominal painwas collected through the use ofdiaries, but the authors did not clarifyhow these diaries were analyzed. Thesystematic review by Horvath et al16

included a third trial with 90 children

FIGURE 1Flow chart showing results of the litera-ture search and study inclusion.

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http://pediatrics.aappublications.org/lookup/suppl/doi:10.1542/peds.2014-2123/-/DCSupplemental

TABLE 1 Study Characteristics of Included Studies

Study Participants Intervention Outcome Measures andInstruments

Quality

Fiber supplements and guar gumChristensen36 (1986);

DenmarkChildren aged 3–14 y (N = 40) Fibers (ispaghula husk) vs

placeboAbdominal pain frequency score Low

RAP (at least 10 episodes ofabdominal pain during the last6 wk, organic causes of painwere excluded)

Dosage: Visiblin 5 mL twice daily;crushed crisp bread with 66%fiber

Improvement: ,10 episodes ofpain during the study period

Treatment period: 6 wk

Instrument: pain diary

Feldman et al37 (1985); Canada Children aged 5–15 y (N = 52) Fiber cookies vs placebo Abdominal pain frequency score LowRAP (organic causes of pain were

excluded on the basis ofhistory, examination, andsimple laboratory test results)

Dosage: 5 g of corn fiber percookie; 1 cookie twice daily

Improvement: 50% decrease infrequency of attack

Treatment period: 6 wk Instrument: pain diary

Horvath et al38 (2013); Poland Children aged 7–17 y (N = 90) GNN vs placebo Severity of pain LowIBS, FAP, and functional dyspepsia

(Rome III criteria)Dosage: 2.52 g/d Improvement: no pain or a

decrease $2/6 points onthe FPS-R


Instrument: FPS-RFollow-up: no follow-up

School absenteeismChanges in daily activityInstrument: self-reported at

baseline and final visitRomano et al24 (2013); Italy Children aged 8–16 y (N = 60) PHGG vs placebo IBS symptoms Moderate

IBS-C and IBS-D (Rome III criteria) Dosage: 5 g/d Treatment success:improvement IBS symptomsTreatment period: 4 wk

Instrument: Birmingham IBSSymptom Questionnaire score

Follow-up: 4 wk

Intensity of abdominal painInstrument: Wong-Baker FACES

Pain Rating ScaleFructose and lactoseDearlove et al39 (1983); United

KingdomChildren aged .3 y (N = 21) Lactose vs placebo Abdominal pain NARAP (. 1/4 d in the last 3 mo) Dosage: 2 g/kg Instrument: reported at final

visit (better, worse, same)Treatment period: 2 wkFollow-up: 3 mo

Lebenthal et al40 (1981);United States

Children aged 6–14 y (N = 38) Lactose versus lactose-freeformula

Abdominal pain (severity andfrequency)

NARAP (intermittent episodes of

unexplained abdominal pain,in a 4-mo period)

Dosage: 2dd 200 mL Instrument: pain diaryTreatment period: 6 wkFollow-up: 12 mo

HTGulewitsch et al25 (2013);

GermanyChildren aged 6–12 y (N = 38) HT program consists of 4

sessions: 2 children’s sessionsand 2 parent’s sessions ina weekly sequence

Abdominal pain index LowFAP and IBS (Rome II criteria)

Control: wait-list

Clinical remission: .80%decrease in days of pain,duration, and intensity ofabdominal pain

Treatment duration: 4 wk Instrument: abdominal pain dairyFollow-up: 3 mo Quality of life

Instrument: German KINDLquestionnaire

DisabilityInstrument: Pediatric Pain

Disability IndexSchool absenteeismInstrument: abdominal pain dairy


TABLE 1 Continued


Quality

van Tilburg et al44 (2009);United States

Children aged 6–15 y (N = 34) Standard care + guided imagery;3 biweekly sessions, including1 booster session + 3 dailysessions. Listen to CD with selfexercises $5 d/wk

Improvement of abdominal pain Low

FAP (abdominal pain at leastonce a week in the past 3 mo)

Control: standard care

Treatment response: .50%reduction of abdominal painscore

Treatment period: 2 mo

Instrument: abdominal pain index

Follow-up: 6 mo Quality of lifeInstrument: PedsQL

DisabilityInstrument: Functional

Disability InventorySchool absenteeismInstrument: abdominal pain dairy

Vlieger et al30,32 (2007/2012);the Netherlands

Children aged 8–18 y (N = 53) 6 HT sessions Abdominal pain score LowFAP and IBS (Rome II criteria) Control: Standard medical care +

supportive therapyClinical remission: .80%

decrease of intensity andfrequency of abdominal painTreatment period: 3 mo

Instrument: abdominal pain dairyFollow-up: 1 y and 5 ySchool absenteeismInstrument: abdominal pain dairy

CBTDuarte et al45 (2006); Brazil Children aged 5–14 y (N = 32) 4 monthly sessions of CBT-family Abdominal pain intensity Low

RAP (Apley’s criteria) Control: standard care Instrument: red and white VASTreatment period: 4 mo Abdominal pain frequencyFollow-up: no follow-up Instrument: daily numbers of

pain in pain dairySanders et al46 (1994);

AustraliaChildren aged 7–14 y (N = 44) 6-session CBT-family Abdominal pain intensity Very lowRAP (Apley’s criteria) Control: standard care Instrument: VAS

Treatment period: 8 wkFollow-up: 6 and 12 mo

Robins et al47 (2005); UnitedStates

Children aged 6–16 y (N = 69) 5-session CBT-family + standardcare

Abdominal pain LowRAP (Apley’s criteria)

Control: standard careInstrument: Abdominal pain index

Treatment period: 10 mo DisabilityFollow-up: 3 and 6 mo Instrument: Functional

Disability InventorySchool absenteeismInstrument: Record of school

attendanceLevy et al26,31 (2010/2013);

United StatesChildren aged 7–17 y (N = 200) 3-session social learning +

CBT-familyAbdominal pain intensity Very low

RAP ($3 episodes of abdominalpain during a 3-mo period) Control: education + support

intervention

Instrument: FPS-R


Disability

Follow-up: 12 mo

Instrument: FunctionalDisability Inventory

Alfvén and Lindstrom48 (2007);Sweden

Children aged 6–18 y (N = 48) Psychological + psychotherapy Abdominal pain intensity Very lowRAP (Apley’s criteria) Control: physiotherapy Instrument: VAS

Treatment period: at least 2sessions, according to theexpressed needs

Pain score at 1-year follow-up

Follow-up: 12 mo

Instrument: VAS + duration(min) + frequency (per week)

Humphreys and Gevirtz49 (2000);United States

Children aged 4–18 y (N = 64) 4 groups: Abdominal pain intensity ModerateRAP 1. Fiber + biofeedback + CBT +

parental supportInstrument: VAS

2. Fiber + biofeedback + CBTSchool absenteeism

3. Fiber + biofeedbackInstrument: Record of school

attendance4. FiberTreatment period: 8-session CBTDosage: 10+ g/d fiber cookies or barsFollow-up: no follow-up


(aged 7–17 years) receiving 4 weeksof glucomannan or identicalplacebo.38 Pain severity was assessedby using the Faces Pain Scale–Revised(6 faces ranging from relaxed tointense pain).51 School absenteeismand changes in daily activities wereself-reported. The primary outcome

in all studies was degree ofimprovement based on abdominalpain frequency or intensity. Afterpooling, there was no significantdifference between the fiber group inexperiencing “no pain” and/or“satisfactory improvement” (52.4%)and the placebo group (43.5%)

(RR: 1.17 [95% CI: 0.75 to 1.81]).Concerning secondary outcomes, nosignificant differences for schoolabsenteeism (10% vs 14%; P = .56)or daily activities (27% vs 19%;P = .37) after glucomannantreatment compared with placebowere found.38

TABLE 1 Continued


Quality

Groß and Warschburger28

(2013); GermanyChildren aged 6–12 y (N = 29) 6-session CBT (group sessions) +

listen to CD with self exercisesAbdominal pain intensity Low

CAP (Rome III criteria)Control: wait-list

Instrument: VAS

Treatment period: 2 mo Abdominal pain frequency (timesper day)/duration (hours perday)

Follow-up: 3 mo

Instrument: pain diaryQuality of lifeInstrument: PedsQL

WSDWallander et al29 (2011);

United StatesChildren aged 11–17 y (N = 63) WSD + standard care: 3 writing

sessions of 20 minAbdominal pain frequency Low

RAP (Apley’s criteria)Control: standard care

Instrument: abdominal painfrequency rating

Treatment period: 5 d Quality of lifeFollow-up: 6 mo Instrument: PedsQL

ProbioticsBausserman and Michail41

(2005); United StatesChildren aged 6–17 y (N = 64) LGG versus placebo Abdominal pain severity ModerateIBS (Rome II criteria) Dosage:1010 CFU, twice daily Responders: decreased pain

score of $1 pointTreatment period: 6 wkInstrument: severity of

symptom scaleFollow-up: no follow-up

Francavilla et al43 (2010); Italy Children aged 5–14 y (N = 141) LGG vs placebo Abdominal pain (frequency ⁄severity)

ModerateIBS and FAP (Rome II criteria) Dosage: 3 3 109 CFU, twice daily

Treatment success: a decreaseof at least 50% in thenumber of episodes andintensity of pain


Instrument: VAS

Follow-up: 8 wk

Gawro�nska et al42 (2007);Poland

Children aged 6–16 y (N = 104) LGG versus placebo Abdominal pain intensity ModerateFAP, functional dyspepsia, and IBS Dosage: 3 3 109 CFU, twice daily Improvement: no pain or

a change in the FPS-R by atleast 2 faces

(Rome II criteria) Treatment period: 4 wk

Instrument: FPS-RFollow-up: no follow-up

School absenteeismInstrument: Record of school

attendanceGuandalini et al27 (2010); Italy

and IndiaChildren aged 4–18 y (N = 59) VSL#3 vs placebo Abdominal pain score (frequency

and intensity)Very low

IBS (Rome II criteria) Dosage: 4–11 y, 1 sachet; 12–18 y,2 sachets Responders: decreased pain

score of $1 pointTreatment period: 6 wkInstrument: self-administered

questionnaireFollow-up: no follow-up

Alternative medicineKuttner et al50 (2006); Canada Children aged 11–18 y (N = 25) Yoga intervention for 1 h followed

by daily home practice guidedby a video

Abdominal pain intensity Very lowIBS (Rome I criteria)

Control: wait-list

Instrument: numeric rating scale


Disability

Follow-up: no follow-up

Instrument: FunctionalDisability Inventory

CAP, chronic abdominal pain; FD, functional dyspepsia; FPS-R, Faces Pain Scale–Revised; GNN, glucomannan; IBS-C, irritable bowel syndrome, constipation predominant; IBS-D, irritablebowel syndrome, diarrhea predominant; NA, not applicable; PedsQL, Pediatric Quality of Life Inventory.


Romano et al24 enrolled 60 patients(aged 8–16 years) and compared4 weeks of partially hydrolyzed guargum (PHGG), a water-soluble, dietaryfiber, with placebo. Symptoms wereassessed by using the BirminghamIBS Symptom Questionnaire, whichcontains questions on frequency ofIBS symptoms (0 = none, 5 = all thetime),52 and the Wong-Baker FACESPain Rating Scale, which was used toevaluate abdominal pain severity(0 = no hurt, 5 = hurts worst).53 Theprimary outcome was reduction inthe frequency and intensity of IBSsymptoms. Improvement in thefrequency of IBS symptoms wassignificantly more likely in the PHGGgroup compared with the controlgroup (43% vs 5%; P = .025) after8 weeks. Effects on pain intensitywere not significant.

Three studies assessed adverseeffects.24,37,38 Unknown smallnumbers of children in both groupsreported gas or diarrhea in the trialby Feldman et al.37 Horvath et al38

and Romano et al24 reported noadverse effects.

Lactose-Free Diet

Huertas-Ceballos et al15 included 2trials evaluating a lactose-free diet inRAP.39,40 Lebenthal et al40 enrolled95 participants. After an intestinalbiopsy was conducted, those patientswith abnormal lactase activity(12–20 U) were excluded: 69children received 6 weeks of lactose-containing or lactose-free infantformula. Abdominal pain wasdocumented in diaries by parents.Remarkably, 31 children wereexcluded due to a lack of compliance;38 children remained. A lactosetolerance test was performed, theresults of which were used to dividechildren into 2 groups: lactosemalabsorbers (n = 21) and lactoseabsorbers (n = 17). Increasedsymptoms were described in 48% ofthe lactose malabsorbers and 24% ofthe lactose absorbers after lactoseintake; however, P values were notreported. Forty of the 69 children

continued with a 12-month lactose-free diet. Improvement of abdominalpain after 12 months was similar inboth groups (40% vs 38%). Detaileddata were not reported, however, andmeta-analysis and GRADE evidenceprofiling were therefore not possible.

Dearlove et al39 included 21 childrenwith RAP in a double-blind, singlecrossover study. After 2 weeks ofcollecting baseline data, all childrenunderwent a 2-week lactose-free diet,followed by another 2 weeks oflactose tonic (2 g/kg) or similarlyflavored placebo. Primary andsecondary outcomes were notspecified. After 3 months, parentswere asked whether their child’ssymptoms (including abdominalpain) were better, worse, or thesame. There was no difference inthe number of children claiming relieffrom the lactose-free orlactose-containing formula.

Hypnotherapy

One systematic review11 (including 2RCTs32,44) and 1 RCT25 evaluated theeffects of HT for FAP and IBS. Twostudies examined HT bytherapists25,32 and 1 examined HTwith self exercises on a CD.44 Allstudies used diaries to assess painintensity and frequency. Gulewitschet al25 recalculated pain scores intoan abdominal pain index. Theabdominal pain index, disability, andschool absenteeism were the primaryoutcomes. Clinical remission wasdefined as a .80% decrease on theabdominal pain index: 55% (11 of 20)of children showed clinical remissionafter HT, compared with 5.6%(1 of 18) of wait-list control subjects(RR: 9.90 [95% CI: 1.14 to 69.28]).

Vlieger et al30,32 included 53 childrenin their research. Clinical remission,defined as a .80% reduction inabdominal pain scores, was theprimary outcome. After 3 months ofHT, 59% showed clinical remissioncompared with 12% receivingstandard care (P , .001). Differencespersisted after 1 year (85% vs 25%;

P , .001) and after 5 years (68% vs20%; P = .005).

Van Tilburg et al44 compared 19children receiving 2 months ofstandard care plus HT through selfexercises on a CD with 15 childrenreceiving standard care. Primary orsecondary outcomes were notspecified. Efficacy was based on anabdominal pain index,54 with higherscores indicating more abdominalpain (range: 0–40). After treatment,children receiving HT reached animprovement of 9.7 points comparedwith 3.1 points in the control subjects(P = .02). Significantly more childrenresponded to HT compared withcontrol subjects (63% vs 27%;P = .03). At 6 months’ follow-up,beneficial effects persisted in 62.5%of the HT group.

Two trials assessed quality of life, butthe results were conflicting.25,44 Toevaluate this secondary outcome,Gulewitsch et al25 used the validatedGerman KINDL questionnaire. Nosignificant effects were reported bychildren (P = .120) or parents(P = .678) compared with controlsubjects. Van Tilburg et al44

demonstrated a significant quality oflife improvement compared withstandard care (P = .049), measured byusing the validated Pediatric Qualityof Life Inventory. Two studiesreported significant improvement indisability.25,44 Gulewitsch et al usedthe Pediatric Pain Disability Index toassess impairment in 12 dailyactivities. HT had a significantbeneficial effect on the self-reporteddisability compared with controlsubjects (MD: –9.14 [95% CI: –14.41to –3.87]).25 Van Tilburg et al usedthe Functional Disability Inventory.Children receiving HT exhibiteda significant reduction in disabilitycompared with control subjects(P = .01).

Two studies did not describedifferences in school absenteeismbetween either treatment group.32,44

In 1 trial, school absenteeism wasseldom reported, and therefore no


calculation was performed.25 Onechild dropped out because oftransient headaches after listening tothe CD.44 Gulewitsch et al25 reportedno adverse effects.

Cognitive Behavioral Therapy

Two systematic reviews12,22

(including 6 RCTs31,45–49) and1 RCT28 were included in theassessment of the various CBTmethods. Four trials evaluated theefficacy of family-focused CBT(ie, CBT-family).31,45–47 A visualanalog scale (VAS)45,46 and the FacesPain Scale–Revised31 were used toassess pain intensity. Robins et al47

used the abdominal pain index forassessments. Only Levy et al31

specified primary outcomes, whichwere abdominal pain intensity anddisability scores. A significantlyhigher proportion of children in thetrial by Sanders et al46 were pain freeafter CBT-family compared withstandard care (MD: –3.61 [95%CI: –5.76 to –1.46]); these changespersisted at 6 months (P = .02) buthad disappeared at the 12-monthfollow-up. Duarte et al45 reportedsignificantly decreased abdominalpain frequency at 3 months’ follow-up (P = .001), but no effect was seenfor pain intensity. In the study byRobins et al,47 CBT-family added tostandard care resulted ina significantly lower abdominal painindex compared with standard carealone (P , .05), with continuingeffects at 6 and 12 months offollow-up. Levy et al31 comparedCBT-family with education andsupport intervention in 200 children.A significant reduction in painintensity as indicated by parents wasreported after 3 sessions ofCBT-family (P , .01). This reductionpersisted for 12 months but was notsignificant when reported bychildren.26 There was no beneficialeffect of CBT-family for disability,31,47

but a significant improvement inschool absenteeism was reportedafter CBT-family plus standard care(P = .047).47

Two studies evaluated the effects ofindividual CBT. Alfvén andLindstrom48 randomized children toundergo CBT plus physiotherapy(n = 25) or physiotherapy alone(n = 23). Pain intensity score (1–3),frequency score (1–3), and durationscore (1–3) were summed intoindividual pain scores ranging from3 to 9. Pain score reduction at the1-year follow-up was not significantlydifferent between groups (46% vs44%; P value not reported).Humphreys and Gevirtz49 divided64 patients (aged 4–18 years) into4 groups to compare CBT, fibersupplements, biofeedback, andparental support in differentcombinations. Children kept diariesand reported pain intensity by usinga VAS; the primary outcome was thenumber of self-reported pain-freedays. Results of the first 3 groups(CBT, biofeedback, and parentalsupport) were combined andcompared with a group receivingfiber supplements. After treatment,33 (72%) of 46 children in theintervention groups were pain freecompared with 1 (7.1%) of 14 childrentaking fiber supplements only (OR:33.0 [95% CI: 3.9 to 278.5]).22

Humphreys and Gevirtz investigatedschool absenteeism and reportedsignificant effects favoring CBT.

Groß and Warschburger28 comparedchildren in the CBT group sessions(n = 15) versus wait-list control subjects(n = 14). Pain intensity was assessed byusing a VAS. Although primaryoutcomes on pain intensity (P = .001),frequency (P = .003), and duration(P = .002) significantly improved afterCBT, only pain duration was stillsignificant at 3 months’ follow-up(P = .014). Quality of life was measuredas a secondary outcome by using thePediatric Quality of Life Inventory. Asignificant improvement favoring CBTwas reported on physical functioning(P , .001), psychological functioning(P = .003), social functioning (P = .044),and school functioning (P = .012).However, results disappeared after3 months of follow-up.

Written Self-Disclosure

Wallander et al29 evaluated WSD inaddition to standard care in 63children (aged 11–18 years) withRAP. In three 20-minute sessions,patients were asked to write abouttheir “deepest thoughts and feelingsabout the most distressing experiencein their life.” Primary and secondaryoutcomes were not specified. Sevenpatients were lost to follow-up andwere excluded from analyses.Abdominal pain frequency was ratedby using a 6-point scale. Althoughthere were no differences at3 months, pain frequency wassignificantly less after WSD andstandard care at the 6-month follow-up compared with standard carealone (F [1,51] = 6.50, P = .014,Cohen’s d = 0.61). Physical andpsychosocial quality of life wasmeasured by using the PediatricQuality of Life Inventory, and nosignificant differences were reported.

Prebiotics or Probiotics

One systematic review18 (including 3RCTs41–43) evaluated the effects ofLactobacillus rhamnosus GG (LGG)compared with placebo. Data werepooled by Horvath et al for treatmentresponders and treatment success,which were secondary outcomes.Bausserman and Michail41 classifiedchildren as responders if abdominalpain severity decreased $1 point ona 4-point Likert scale. Francavillaet al43 used a VAS and definedtreatment success as a decrease of.50% of pain episodes and intensity.Gawro�nska et al42 defined treatmentsuccess as no pain or change in theFaces Pain Scale–Revised by$2 faces.LGG supplementation was associatedwith significantly more treatmentresponders (67%) compared withplacebo (51%) (n = 290; RR: 1.31[95% CI: 1.08 to 1.59]; numberneeded to treat: 7 [95% CI: 4 to22]).18 Subgroup analysis showedresults being mainly applicable forIBS (n = 167; RR: 1.70 [95% CI: 1.27to 2.27]; number needed to treat:4 [95% CI: 3 to 8]). Guandalini et al27


conducted a crossover trial,comparing 6 weeks of VSL#3 versusplacebo in 59 children with IBS.VSL#3 is a probiotic mixturecomprising 8 different strains ofBifidobacterium, Lactobacillus, andStreptococcus. After a 2-weekwashout period, each patientswitched to the other group foranother 6 weeks of treatment.Abdominal pain was measured asa secondary outcome: frequency andintensity were rated on a 5-pointLikert scale. After treatment,a significant reduction in theabdominal pain score of 1.0 6 0.2was reported in the VSL#3 groupversus 0.5 6 0.2 in control subjects(P , .05). One study evaluated schoolabsenteeism, but no significantdifference was found.42 No adverseeffects of LGG were reported,although it was unclear in 2 studieshow adverse effects wereassessed.41,42

No studies were included onprebiotics.

Alternative Medicine

One study of the systematic review byBirdee et al23 was included regardingalternative therapy. Kuttner et al50

compared 14 children receiving yogaversus 11 wait-list control subjects.After 4 weeks, questionnaires werecompleted, and control subjectsreceived 4 weeks of yoga andcompleted additional questionnaires.Pain intensity was measured ona numeric scale of 0 to 10. Resultsbefore the crossover phase were notreported because of baselinedifferences. Functional disabilitydecreased after yoga but increasedin control subjects (MD: –9.60[95% CI: –19.66 to 0.46]). Primaryor secondary outcomes were notspecified.

No studies were included evaluatingacupuncture, homeopathy,mind–body therapy, ormusculoskeletal manipulations suchas osteopathic and chiropracticmanipulations.

DISCUSSION

This systematic review includes 24studies that were of very low tomoderate methodologic quality. Someevidence was found indicatingbeneficial effects of PHGG, HT, CBT,and probiotics (LGG and VSL#3). Nobeneficial effects were reported forfiber supplementation other thanPHGG and a lactose-restricted diet. Nostudies were included on lifestyleadvice, other dietary advice, orprebiotics. No serious adverse effectswere reported.

Dietary interventions are frequentlyused in AP-FGIDs because manypatients and some physiciansconsider symptoms to be mealrelated.55 Fiber supplementation isbelieved to be helpful because itsoftens stools and enhances colonictransit.56 However, studies in childrenand adolescents evaluating ispaghulahusk and glucomannan found nofavorable effects.36,38 Improvement inabdominal pain frequency wasreported after administration of cornfiber,37 but questions were raisedwhether the statistical analyses wereadequate. Re-analyses by Huertas-Ceballos et al15 failed to replicate thefindings. Adult studies producedconflicting results and a meta-analysis reported only beneficialeffects for ispaghula husk.56 The maincomponent of PHGG isgalactomannan, which softens stool,improves fecal output, and increasesbulk capacities.57 PHGG treatment inIBS children found a reducedfrequency in IBS symptoms, but painintensity was not decreased.24

Results of an open-label PHGG trial inadult patients with IBS producedsignificant improvements ingastrointestinal symptoms, quality oflife, and psychological distress, butthe effects tended to diminish afterthe 12-week treatment period.57

Malabsorption and intolerance tocarbohydrates such as fructose andlactose are believed to causesymptoms such as bloating, diarrhea,and abdominal pain.55 However,

neither lactose nor fructoseintolerance was established asa cause of pain in 220 children withRAP in a recent study,58 and lactoserestriction did not improve symptomsin pediatric trials.39,40 Recently, dietsof low fermentable oligosaccharides,disaccharides, monosaccharides, andpolyols (FODMAP) have beenextensively studied in adults.FODMAPs are poorly absorbed short-chain carbohydrates, which maycause gas production, bloating, andabdominal pain.59 A low FODMAPdiet seemed beneficial in adult IBStrials, but due to heterogeneity instudy design and outcomes andbecause of unknown long-term safetyand efficacy, definitive conclusionscannot be drawn.60 Recently,a randomized, double-blind,crossover trial in 33 children with IBSreported improvement in abdominalpain after receiving a 48-hour lowFODMAP diet.61 Although theseresults seem promising, more long-term studies are needed to furtherassess the efficacy and safety of a lowFODMAP diet in children andadolescents.

In HT, suggestions toward controland normalization of gut functioning,ego strengthening, and stressreduction are conveyed to patientsafter inducing a hypnotic state.62

Results of studies in children andadolescents found significantly lowerabdominal pain levels and symptomscores after HT, either throughindividual or group sessions withtherapists or with self exercises ona CD.25,32,44 Effects persist up to5 years after treatment.30 Results arein accordance with adult IBS trialsshowing that HT is superior toa variety of control treatments, withlong-lasting effects.63–66 Workingmechanisms of HT are still poorlyunderstood, but outcomes of adultstudies hypothesize that HT affectsboth physiologic processes, such ascolonic motility and pain-processingbrain regions, and psychologicalfactors, such as stress anddysfunctional cognitions.67–69


CBT aims to change attitudes,cognitions, and behavior that mayplay a role in generating ormaintaining symptoms and iseffective in improving pain and otherIBS symptoms in adults.70 Trials inchildren and adolescents also indicatebeneficial effects of CBT, especiallyCBT-family, in improving pain anddisability, and the effects seem to belong-lasting.26,28,31,45–47 Results ofthe trial by Levy et al are of particularinterest because it included 200children and adolescents.31 An RCTon individual CBT published shortlyafter the literature search for thepresent systematic review showedimprovement in 60% of children withFAP after CBT, but the results did notdiffer compared with standard care(including 6 supportive sessions withthe pediatric gastroenterologist).71

However, children receiving CBTreported significantly fewersymptoms of anxiety or depressioncompared with children receivingstandard care.

WSD targets psychosocial stress andmay work through changingexpression and increasing insightabout emotions. It is reportedlyeffective in a wide variety of adultorganic and functional disorders.72

WSD in addition to standard caresignificantly reduced pain frequencyafter 6 months in pediatric RAP butnot after 3 months. Although furtherresearch is needed, WSD may bea useful adjunct to other treatmentregimens because it can be easilyintegrated, requires little training,and has low costs.29

Probiotics are beneficial species ofbacteria that may improve AP-FGIDsymptoms by preventing overgrowthof potentially pathogenic bacteria,maintaining integrity of gut mucosa,and/or altering intestinalinflammatory responses.73 RCTs inchildren and adolescents evaluatingLGG and VSL#3 in FAP, IBS, andfunctional dyspepsia indicatebeneficial effects over placebo, butprobiotics seem mostly effective in

IBS.27,41–43 Probiotics also seemeffective in adults with AP-FGIDs, butfuture research must clarify whichprobiotic strains are most effective.74

Although .40% of children with IBSand FAP use complementary andalternative medicine,75 data arelacking on the efficacy and safety ofalmost all forms of this treatment inchildren and adolescents. Yoga mayaddress psychosocial factors anddecrease stress.76 Kuttner et al50

reported significantly lower levels offunctional disability andgastrointestinal symptoms after yoga,but it is noteworthy that P values ,.1were considered reflective ofstatistical trends worthy ofinterpretation. However, a pilot studyin children and adolescents aged 8 to18 years with IBS and FAP also foundsignificant short-term improvementin abdominal pain frequency andintensity.76 It thus seems worthwhileto further explore the efficacy of yoga.Because treatment protocols in CBT,HT, and yoga all incorporaterelaxation exercises, one mighthypothesize that relaxation trainingalone can also be beneficial inAP-FGIDs. This therapeutic approachmay be interesting to address infuture research because it has beenshown to be effective in children andadolescents with recurrent headachesas well.77

The methodologic quality of theincluded studies varied from very lowto moderate, and the results shouldtherefore be interpreted cautiously.The low quality was mainly due tosmall sample sizes, lack of adequatefollow-up, substantial dropout rates,or considerable risk of bias. However,it should be taken into account thatblinding of patients and caregivers isnot possible in psychologicaltherapies such as HT or CBT. By usingvalidated diagnostic criteria forAP-FGIDs, applicability of results isincreased, which strengthens theresults. Due to considerableheterogeneity of studies, meta-analysis could only be conducted for

fiber supplementation and probiotics.Other possible limitations of thissystematic review include thepossibility of publication bias andlanguage restriction to English.However, by conductinga comprehensive andcontemporaneous literature search,we attempted to minimize the risk ofmissing relevant studies. Use ofa wide variety of definitions forclinical improvement also hampersthe interpretation of results. Clinicalrelevance of a 1-point reduction ona 4-point Likert scale may bequestioned,41 whereas an 80%reduction in abdominal painfrequency and intensity scores seemsoverly conservative.30,32

Unfortunately, a standard definitionof improvement for therapeuticstudies on AP-FGIDs is lacking.Consensus on a standard definition isnecessary because it increases thehomogeneity of future trials andallows better comparison of results.In addition, performing analyses onnumber needed to treat and RR isoften restricted because most RCTsfail to report on numbers orpercentages of patients experiencingsignificant improvement.

A limited number of RCTs (n = 8)reported on adverse effects, therebyhindering interpretation of results onsafety. However, in those studies, noserious adverse effects were shown,apart from a small number of childrenreporting gas or diarrhea.37 Ininterpreting FGID trials, the placeboeffect may play an important role.Placebo responses in trials of adultswith IBS vary from 16.0% to 71.4%,78

and high placebo rates up to 53%were reported in RCTs on childrenand adolescents.41,43,79 High placeboresponses may also display naturalcourse of FGIDs with fluctuatingsymptoms.80 Improving the patient-practitioner relationship and activelistening approaches are essential inmediating placebo responses. Thismay be especially important innonpharmacologic therapies in which


contact with therapists is mostlyfrequent.81,82

CONCLUSIONS

To date, high-quality studies onnonpharmacologic treatments inpediatric AP-FGIDs are lacking, andthe need for these studies is evident.However, available evidence indicatesbeneficial effects of HT, CBT andprobiotics (LGG and VSL#3) in somechildren. Data on fibersupplementation for children andadolescents with AP-FGIDs areinconclusive, but PHGG may be an

option. No serious adverse effectswere reported.

Because symptoms may resolvewithout active treatment ina significant proportion of children,the first step in management mayconsist of physician reassurance andeducation. However, approximatelyone-third of children continue toexperience symptoms.83 Cliniciansmay consider HT, CBT, or probiotics(LGG and VSL#3), especially inchildren with persistent symptoms.Additional high-quality studies arerequired in children with mild as wellas severe symptoms to further assess

the effectiveness of nonpharmacologictherapies and to identify factorspredicting response, with the goal ofoptimizing and tailoring individualtreatments. Because abdominal pain isthe key symptom in AP-FGIDs andto decrease heterogeneity, weemphasized the importance ofincluding abdominal pain severity,frequency, and/or intensity asa primary outcome measure in trialsevaluating nonpharmacologictreatments for AP-FGIDs. In addition,adverse effects need to bereported systematically to betterassess safety.

Address correspondence to Juliette M.T.M. Rutten, MD, Emma Children’s Hospital, Academic Medical Center, Room C2-312, PO Box 22700, 1100 DD Amsterdam.

E-mail: [email protected]

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2015 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

REFERENCES

1. Rasquin A, Di Lorenzo C, Forbes D, et al.Childhood functional gastrointestinaldisorders: child/adolescent.Gastroenterology. 2006;130(5):1527–1537

2. Chitkara DK, Rawat DJ, Talley NJ. Theepidemiology of childhood recurrentabdominal pain in Western countries:a systematic review. Am J Gastroenterol.2005;100(8):1868–1875

3. Chiou E, Nurko S. Management offunctional abdominal pain and irritablebowel syndrome in children andadolescents. Expert Rev GastroenterolHepatol. 2010;4(3):293–304

4. Di Lorenzo C, Colletti RB, Lehmann HP,et al; AAP Subcommittee; NASPGHANCommittee on Chronic Abdominal Pain.Chronic abdominal pain in children:a technical report of the AmericanAcademy of Pediatrics and the NorthAmerican Society for PediatricGastroenterology, Hepatology andNutrition. J Pediatr Gastroenterol Nutr.2005;40(3):249–261

5. Howell S, Poulton R, Talley NJ. Thenatural history of childhood abdominal

pain and its association with adultirritable bowel syndrome: birth-cohortstudy. Am J Gastroenterol. 2005;100(9):2071–2078

6. Dhroove G, Chogle A, Saps M. Amillion-dollar work-up for abdominalpain: is it worth it? J PediatrGastroenterol Nutr. 2010;51(5):579–583

7. Drossman DA. The functionalgastrointestinal disorders and the RomeIII process. Gastroenterology. 2006;130(5):1377–1390

8. Campo JV, Bridge J, Ehmann M, et al.Recurrent abdominal pain, anxiety, anddepression in primary care. Pediatrics.2004;113(4):817–824

9. Walker LS, Smith CA, Garber J, Claar RL.Appraisal and coping with dailystressors by pediatric patients withchronic abdominal pain. J PediatrPsychol. 2007;32(2):206–216

10. Levy RL, Olden KW, Naliboff BD, et al.Psychosocial aspects of the functionalgastrointestinal disorders.Gastroenterology. 2006;130(5):1447–1458

11. Rutten JM, Reitsma JB, Vlieger AM,Benninga MA. Gut-directed hypnotherapyfor functional abdominal pain orirritable bowel syndrome in children:a systematic review. Arch Dis Child. 2013;98(4):252–257

12. Eccleston C, Palermo TM, de C WilliamsAC, et al. Psychological therapies for themanagement of chronic and recurrentpain in children and adolescents.Cochrane Database Syst Rev. 2012;12:CD003968

13. Chey WD. The role of food in thefunctional gastrointestinal disorders:introduction to a manuscript series. AmJ Gastroenterol. 2013;108(5):694–697

14. Gibson PR, Shepherd SJ. Food choice asa key management strategy for functionalgastrointestinal symptoms. Am JGastroenterol. 2012;107(5):657–666, quiz 667

15. Huertas-Ceballos A, Logan S, Bennett C,Macarthur C. Dietary interventions forrecurrent abdominal pain (RAP) andirritable bowel syndrome (IBS) inchildhood. Cochrane Database Syst Rev.2008;23(1):CD003019


mailto:[email protected]

16. Horvath A, Dziechciarz P, Szajewska H.Systematic review of randomizedcontrolled trials: fiber supplements forabdominal pain-related functionalgastrointestinal disorders in childhood.Ann Nutr Metab. 2012;61(2):95–101

17. Huertas-Ceballos A, Logan S, Bennett C,Macarthur C. Pharmacologicalinterventions for recurrent abdominalpain (RAP) and irritable bowel syndrome(IBS) in childhood. Cochrane DatabaseSyst Rev. 2008;23(1):CD003017

18. Horvath A, Dziechciarz P, Szajewska H.Meta-analysis: Lactobacillus rhamnosusGG for abdominal pain-related functionalgastrointestinal disorders in childhood.Aliment Pharmacol Ther. 2011;33(12):1302–1310

19. Guyatt GH, Oxman AD, Vist GE, et al;GRADE Working Group. GRADE: anemerging consensus on rating quality ofevidence and strength ofrecommendations. BMJ. 2008;336(7650):924–926

20. Higgins JPT, Altman DG, Gøtzsche PC,et al; Cochrane Bias Methods Group;Cochrane Statistical Methods Group. TheCochrane Collaboration’s tool forassessing risk of bias in randomisedtrials. BMJ. 2011;343:d5928

21. Schünemann H, Oxman A, Vist G, et al.Interpreting results and drawingconclusions. In: Higgins JPT, Green S,eds. Cochrane Handbook for SystematicReviews of Interventions Version 510(updated March 2011); The CochraneCollaboration 2012. Available at:www.cochrane-handbook.org. AccessedDecember 19, 2014

22. Huertas-Ceballos A, Logan S, Bennett C,Macarthur C. Psychosocial interventionsfor recurrent abdominal pain (RAP) andirritable bowel syndrome (IBS) inchildhood. Cochrane Database Syst Rev.2008;(1):CD003014

23. Birdee GS, Yeh GY, Wayne PM, Phillips RS,Davis RB, Gardiner P. Clinicalapplications of yoga for the pediatricpopulation: a systematic review. AcadPediatr. 2009;9(4):212–, e1–e9

24. Romano C, Comito D, Famiani A,Calamarà S, Loddo I. Partially hydrolyzedguar gum in pediatric functionalabdominal pain. World J Gastroenterol.2013;19(2):235–240

25. Gulewitsch MD, Müller J, Hautzinger M,Schlarb AA. Brief hypnotherapeutic-

behavioral intervention for functionalabdominal pain and irritable bowelsyndrome in childhood: a randomizedcontrolled trial. Eur J Pediatr. 2013;172(8):1043–1051

26. Levy RL, Langer SL, Walker LS, et al.Twelve-month follow-up of cognitivebehavioral therapy for children withfunctional abdominal pain. JAMA Pediatr.2013;167(2):178–184

27. Guandalini S, Magazzù G, Chiaro A, et al.VSL#3 improves symptoms in childrenwith irritable bowel syndrome:a multicenter, randomized, placebo-controlled, double-blind, crossover study.J Pediatr Gastroenterol Nutr. 2010;51(1):24–30

28. Groß M, Warschburger P. Evaluation ofa cognitive-behavioral pain managementprogram for children with chronicabdominal pain: a randomized controlledstudy. Int J Behav Med. 2013;20(3):434–443

29. Wallander JL, Madan-Swain A, Klapow J,Saeed S. A randomised controlled trial ofwritten self-disclosure for functionalrecurrent abdominal pain in youth.Psychol Health. 2011;26(4):433–447

30. Vlieger AM, Rutten JM, Govers AM,Frankenhuis C, Benninga MA. Long-termfollow-up of gut-directed hypnotherapyvs. standard care in children withfunctional abdominal pain or irritablebowel syndrome. Am J Gastroenterol.2012;107(4):627–631

31. Levy RL, Langer SL, Walker LS, et al.Cognitive-behavioral therapy for childrenwith functional abdominal pain and theirparents decreases pain and othersymptoms. Am J Gastroenterol. 2010;105(4):946–956

32. Vlieger AM, Menko-Frankenhuis C,Wolfkamp SC, Tromp E, Benninga MA.Hypnotherapy for children withfunctional abdominal pain or irritablebowel syndrome: a randomizedcontrolled trial. Gastroenterology. 2007;133(5):1430–1436

33. Sanders MR, Rebgetz M, Morrison M,et al. Cognitive-behavioral treatment ofrecurrent nonspecific abdominal pain inchildren: an analysis of generalization,maintenance, and side effects. J ConsultClin Psychol. 1989;57(2):294–300

34. Hicks CL, von Baeyer CL, McGrath PJ.Online psychological treatment forpediatric recurrent pain: a randomized

evaluation. J Pediatr Psychol. 2006;31(7):724–736

35. Weydert JA, Shapiro DE, Acra SA,Monheim CJ, Chambers AS, Ball TM.Evaluation of guided imagery astreatment for recurrent abdominal painin children: a randomized controlledtrial. BMC Pediatr. 2006;6:29

36. Christensen MF. Recurrent abdominalpain and dietary fiber. Am J Dis Child.1986;140(8):738–739

37. Feldman W, McGrath P, Hodgson C, RitterH, Shipman RT. The use of dietary fiber inthe management of simple, childhood,idiopathic, recurrent, abdominal pain.Results in a prospective, double-blind,randomized, controlled trial. Am J DisChild. 1985;139(12):1216–1218

38. Horvath A, Dziechciarz P, Szajewska H.Glucomannan for abdominal pain-relatedfunctional gastrointestinal disorders inchildren: a randomized trial. World JGastroenterol. 2013;19(20):3062–3068

39. Dearlove J, Dearlove B, Pearl K,Primavesi R. Dietary lactose and thechild with abdominal pain. Br Med J(Clin Res Ed). 1983;286(6382):1936

40. Lebenthal E, Rossi TM, Nord KS, BranskiD. Recurrent abdominal pain and lactoseabsorption in children. Pediatrics. 1981;67(6):828–832

41. Bausserman M, Michail S. The use ofLactobacillus GG in irritable bowelsyndrome in children: a double-blindrandomized control trial. J Pediatr. 2005;147(2):197–201

42. Gawro�nska A, Dziechciarz P, Horvath A,Szajewska H. A randomized double-blindplacebo-controlled trial of LactobacillusGG for abdominal pain disorders inchildren. Aliment Pharmacol Ther. 2007;25(2):177–184

43. Francavilla R, Miniello V, Magistà AM,et al. A randomized controlled trial ofLactobacillus GG in children withfunctional abdominal pain. Pediatrics.2010;126(6). Available at: www.pediatrics.org/cgi/content/full/126/6/e1445

44. van Tilburg MA, Chitkara DK, Palsson OS,et al. Audio-recorded guided imagerytreatment reduces functional abdominalpain in children: a pilot study. Pediatrics.2009;124(5). Available at: www.pediatrics.org/cgi/content/full/124/5/e890

45. Duarte MA, Penna FJ, Andrade EM,Cancela CS, Neto JC, Barbosa TF.


http://www.cochrane-handbook.org

http://www.pediatrics.org/cgi/content/full/126/6/e1445




Treatment of nonorganic recurrentabdominal pain: cognitive-behavioralfamily intervention. J PediatrGastroenterol Nutr. 2006;43(1):59–64

46. Sanders MR, Shepherd RW, Cleghorn G,Woolford H. The treatment of recurrentabdominal pain in children: a controlledcomparison of cognitive-behavioralfamily intervention and standardpediatric care. J Consult Clin Psychol.1994;62(2):306–314

47. Robins PM, Smith SM, Glutting JJ, BishopCT. A randomized controlled trial ofa cognitive-behavioral familyintervention for pediatric recurrentabdominal pain. J Pediatr Psychol. 2005;30(5):397–408

48. Alfvén G, Lindstrom A. A new method forthe treatment of recurrent abdominalpain of prolonged negative stress origin.Acta Paediatr. 2007;96(1):76–81

49. Humphreys PA, Gevirtz RN. Treatment ofrecurrent abdominal pain: componentsanalysis of four treatment protocols. JPediatr Gastroenterol Nutr. 2000;31(1):47–51

50. Kuttner L, Chambers CT, Hardial J, IsraelDM, Jacobson K, Evans K. A randomizedtrial of yoga for adolescents withirritable bowel syndrome. Pain ResManag. 2006;11(4):217–223

51. Hicks CL, von Baeyer CL, Spafford PA, vanKorlaar I, Goodenough B. The Faces PainScale-Revised: toward a common metricin pediatric pain measurement. Pain.2001;93(2):173–183

52. Roalfe AK, Roberts LM, Wilson S.Evaluation of the Birmingham IBSsymptom questionnaire. BMCGastroenterol. 2008;8:30

53. Chambers CT, Craig KD. An intrusiveimpact of anchors in children’s facespain scales. Pain. 1998;78(1):27–37

54. Walker LS, Smith CA, Garber J, Van SlykeDA. Development and validation of thepain response inventory for children.Psychol Assessment. 1997;9(4):392–405

55. Simrén M, Månsson A, Langkilde AM,et al. Food-related gastrointestinalsymptoms in the irritable bowelsyndrome. Digestion. 2001;63(2):108–115

56. Ford AC, Talley NJ, Spiegel BM, et al.Effect of fibre, antispasmodics, andpeppermint oil in the treatment ofirritable bowel syndrome: systematicreview and meta-analysis. BMJ. 2008;337:a2313

57. Parisi G, Bottona E, Carrara M, et al.Treatment effects of partially hydrolyzedguar gum on symptoms and quality oflife of patients with irritable bowelsyndrome. A multicenter randomizedopen trial. Dig Dis Sci. 2005;50(6):1107–1112

58. Gijsbers CF, Kneepkens CM, Büller HA.Lactose and fructose malabsorption inchildren with recurrent abdominal pain:results of double-blinded testing. ActaPaediatr. 2012;101(9):e411–e415

59. Shepherd SJ, Lomer MCE, Gibson PR.Short-chain carbohydrates andfunctional gastrointestinal disorders. AmJ Gastroenterol. 2013;108(5):707–717

60. Fedewa A, Rao SS. Dietary fructoseintolerance, fructan intolerance andFODMAPs. Curr Gastroenterol Rep. 2014;16(1):370

61. Chumpitazi B, Tsai C, McMeans A,Shulman R. A low FODMAPs dietameliorates symptoms in children withirritable bowel syndrome: a doubleblind, randomized crossover trial.Gastroenterology. 2014;146(5):S-144

62. Green JP, Barabasz AF, Barrett D,Montgomery GH. Forging ahead: the 2003APA Division 30 definition of hypnosis. IntJ Clin Exp Hypn. 2005;53(3):259–264

63. Webb AN, Kukuruzovic RH, Catto-SmithAG, Sawyer SM. Hypnotherapy fortreatment of irritable bowel syndrome.Cochrane Database Syst Rev. 2007;17(4):CD005110

64. Gonsalkorale WM, Miller V, Afzal A,Whorwell PJ. Long term benefits ofhypnotherapy for irritable bowelsyndrome. Gut. 2003;52(11):1623–1629

65. Lindfors P, Unge P, Nyhlin H, et al. Long-term effects of hypnotherapy in patientswith refractory irritable bowelsyndrome. Scand J Gastroenterol. 2012;47(4):414–420

66. Moser G, Trägner S, Gajowniczek EE, et al.Long-term success of GUT-directed grouphypnosis for patients with refractoryirritable bowel syndrome: a randomizedcontrolled trial. Am J Gastroenterol.2013;108(4):602–609

67. Palsson OS, Turner MJ, Johnson DA,Burnett CK, Whitehead WE. Hypnosistreatment for severe irritable bowelsyndrome: investigation of mechanismand effects on symptoms. Dig Dis Sci.2002;47(11):2605–2614

68. Gonsalkorale WM, Toner BB, Whorwell PJ.Cognitive change in patients undergoinghypnotherapy for irritable bowelsyndrome. J Psychosom Res. 2004;56(3):271–278

69. Faymonville ME, Roediger L, Del Fiore G,et al. Increased cerebral functionalconnectivity underlying theantinociceptive effects of hypnosis. BrainRes Cogn Brain Res. 2003;17(2):255–262

70. Ford AC, Talley NJ, Schoenfeld PS, QuigleyEM, Moayyedi P. Efficacy ofantidepressants and psychologicaltherapies in irritable bowel syndrome:systematic review and meta-analysis.Gut. 2009;58(3):367–378

71. van der Veek SM, Derkx BH, BenningaMA, Boer F, de Haan E. Cognitive behaviortherapy for pediatric functionalabdominal pain: a randomized controlledtrial. Pediatrics. 2013;132(5). Available at:www.pediatrics.org/cgi/content/full/132/5/e1163

72. Frattaroli J. Experimental disclosure andits moderators: a meta-analysis. PsycholBull. 2006;132(6):823–865

73. Quigley EM. Probiotics in functionalgastrointestinal disorders: what are thefacts? Curr Opin Pharmacol. 2008;8(6):704–708

74. Simrén M, Barbara G, Flint HJ, et al;Rome Foundation Committee. Intestinalmicrobiota in functional boweldisorders: a Rome foundation report.Gut. 2013;62(1):159–176

75. Vlieger AM, Blink M, Tromp E, BenningaMA. Use of complementary andalternative medicine by pediatricpatients with functional and organicgastrointestinal diseases: results froma multicenter survey. Pediatrics. 2008;122(2). Available at: www.pediatrics.org/cgi/content/full/122/2/e446

76. Brands MM, Purperhart H, Deckers-Kocken JM. A pilot study of yogatreatment in children with functionalabdominal pain and irritable bowelsyndrome. Complement Ther Med. 2011;19(3):109–114

77. Trautmann E, Lackschewitz H, Kröner-Herwig B. Psychological treatment ofrecurrent headache in children andadolescents—a meta-analysis.Cephalalgia. 2006;26(12):1411–1426

78. Patel SM, Stason WB, Legedza A, et al. Theplacebo effect in irritable bowel






syndrome trials: a meta-analysis.Neurogastroenterol Motil. 2005;17(3):332–340

79. Saps M, Youssef N, Miranda A, et al.Multicenter, randomized, placebo-controlled trial of amitriptyline inchildren with functional gastrointestinaldisorders. Gastroenterology. 2009;137(4):1261–1269

80. Drossman DA, Camilleri M, Mayer EA,Whitehead WE. AGA technical review onirritable bowel syndrome.Gastroenterology. 2002;123(6):2108–2131

81. Kelley JM, Lembo AJ, Ablon JS, et al.Patient and practitioner influences onthe placebo effect in irritable bowelsyndrome. Psychosom Med. 2009;71(7):789–797

82. Kaptchuk TJ, Kelley JM, Conboy LA, et al.Components of placebo effect:randomised controlled trial in patientswith irritable bowel syndrome. BMJ.2008;336(7651):999–1003

83. Gieteling MJ, Bierma-Zeinstra SM, Passchier J,Berger MY. Prognosis of chronic or recurrentabdominal pain in children. J PediatrGastroenterol Nutr. 2008;47(3):316–326

WARMWATERBLUES:WhenIwasateen, Iwouldoccasionallygocodfishingoff thecoast ofMaine orMassachusettswithmy father.Whilewedid not catchparticularlylarge numbers of fish, we always caught enough cod for several dinners. In thosedays, cod was a staple of New England fish restaurants. That has changed. The codpopulation off of the coast of New England has collapsed – so much so that, asreported in The New York Times (U.S.: December 15, 2014), cod fishing has beenbanned since November for six months as regulators decide how to address theproblem.While overfishing has certainly contributed, a problem that cannot easily beaddressedbystateandfederal regulators is thewarmingof theGulfofMainewaters.Historically, the water temperature in the Gulf of Maine had warmed on averageabout onedegree every twodecades or so. In the past decade, thewater haswarmedbyaboutonedegree every twoyears. Thishas led tochanges in the ecosystem.Maineshrimp have fled for colder climates, leading regulators to cancel theMaine shrimpharvest for the second year in a row. Black sea bass, native to warmer southernwaters and previously rarely seen off the coast of Maine, have become abundant.Blue crab, so closely linked to the Chesapeake, has made an appearance. Lobstershavebecomemuchmoreplentifulwithrecordharvests forseveral years inarow,butthe center of the lobster industryhasmovedat least 50miles to thenorth. The toll onthe economyand human lifemay be quite severe. Precluded fromfishing for at leastsix months, Maine’s fishermen have few options to support themselves. This is justanother example of how intertwined humans and animals are with the ecosystemsand the complex interplay between each and all its parts.

Noted by WVR, MD


DOI: 10.1542/peds.2014-2123 originally published online February 9, 2015; 2015;135;522Pediatrics

Benninga and Merit M. TabbersJuliette M.T.M. Rutten, Judith J. Korterink, Leonie M.A.J. Venmans, Marc A.

Systematic ReviewNonpharmacologic Treatment of Functional Abdominal Pain Disorders: A

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DOI: 10.1542/peds.2014-2123 originally published online February 9, 2015; 2015;135;522Pediatrics

Benninga and Merit M. TabbersJuliette M.T.M. Rutten, Judith J. Korterink, Leonie M.A.J. Venmans, Marc A.

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