pediatrics 2011 tabbers 753 61

DOI: 10.1542/peds.2011-0179; originally published online September 26, 2011; 2011;128;753Pediatrics

Merit M. Tabbers, Nicole Boluyt, Marjolein Y. Berger and Marc A. BenningaNonpharmacologic Treatments for Childhood Constipation: Systematic Review

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located on the World Wide Web at: The online version of this article, along with updated information and services, is

of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2011 by the American Academy published, and trademarked by the American Academy of Pediatrics, 141 Northwest Pointpublication, it has been published continuously since 1948. PEDIATRICS is owned, PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

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Nonpharmacologic Treatments for ChildhoodConstipation: Systematic Review

abstractOBJECTIVE: To summarize the evidence and assess the reported qual-ity of studies concerning nonpharmacologic treatments for childhoodconstipation, including fiber, fluid, physical movement, prebiotics, pro-biotics, behavioral therapy, multidisciplinary treatment, and forms ofalternative medicine.

METHODS: We systematically searched 3 major electronic databasesand reference lists of existing reviews. We included systematic reviewsand randomized controlled trials (RCTs) that reported on nonpharma-cologic treatments. Two reviewers rated the methodologic qualityindependently.

RESULTS: We included 9 studies with 640 children. Considerable het-erogeneity across studies precluded meta-analysis. We found no RCTsfor physical movement, multidisciplinary treatment, or alternativemedicine. Some evidence shows that fiber may be more effective thanplacebo in improving both the frequency and consistency of stools andin reducing abdominal pain. Compared with normal fluid intake, wefound no evidence that water intake increases or that hyperosmolarfluid treatment is more effective in increasing stool frequency or de-creasing difficulty in passing stools. We found no evidence to recom-mend the use of prebiotics or probiotics. Behavioral therapy with lax-atives is not more effective than laxatives alone.

CONCLUSIONS: There is some evidence that fiber supplements aremore effective than placebo. No evidence for any effect was found forfluid supplements, prebiotics, probiotics, or behavioral intervention.There is a lack of well-designed RCTs of high quality concerning non-pharmacologic treatments for children with functional constipation.Pediatrics 2011;128:753–761

AUTHORS: Merit M. Tabbers, MD, PhD,a Nicole Boluyt, MD,PhD,b Marjolein Y. Berger, MD, PhD,c and Marc A.Benninga, MD, PhDa

Departments of aPediatric Gastroenterology and Nutrition andbPediatrics, Emma’s Children’s Hospital/Academic MedicalCentre, Amsterdam, Netherlands; and cDepartment of GeneralPractice, University Hospital Groningen, Groningen, Netherlands

KEY WORDSchildhood constipation, systematic review, nonpharmacologictreatments, complementary treatment, alternative treatment

ABBREVIATIONRCT—randomized controlled trial

Drs Tabbers and Berger contributed equally to this work.

www.pediatrics.org/cgi/doi/10.1542/peds.2011-0179

doi:10.1542/peds.2011-0179

Accepted for publication Jun 13, 2011

Address correspondence to Merit M. Tabbers, MD, PhD,Department of Pediatric Gastroenterology and Nutrition, EmmaChildren’s Hospital/Academic Medical Centre, H7-250, PO Box22700, 1100 DD Amsterdam, Netherlands. E-mail: [email protected]

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

Copyright © 2011 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they haveno financial relationships relevant to this article to disclose.

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Chronic constipation is a commonproblem in childhood; the estimatedprevalence is 3% in the Westernworld.1 It is a debilitating conditioncharacterized by infrequent painfuldefecation, fecal incontinence, and ab-dominal pain. It causes distress to thechild and family and can result in se-vere emotional disturbances and fam-ily discord.

The cause of constipation is multifac-torial and is not well understood. Cri-teria for a definition of functional con-stipation vary widely and are basedmostly on a variety of symptoms, in-cluding decreased frequency of bowelmovements, fecal incontinence, and achange in stool consistency.2

Constipation is difficult to treat for themajority of patients and indeed is along-lasting problem. Approximately50% of all children who were moni-tored for 6 to 12 months were found torecover and successfully discontinuedlaxative therapy.3 A study in a tertiaryhospital showed that, despite intensivemedical and behavioral therapy, 30%of patients who developed constipa-tion before the age of 5 years contin-ued to have severe complaints ofconstipation, infrequent painful defe-cation, and fecal incontinence beyondpuberty.4

The first step in treatment consists ofeducation, dietary advice, and behav-ioral modifications.2 If these are not ef-fective, then laxatives are prescribed.Although there is a lack of placebo-controlled trials showing the effective-ness of laxatives, their use in clinicalpractice is widely accepted.5 Thechronic nature of the disease, in com-bination with a lack of clear effects oflaxatives and parents’ general fear ofadverse effects with daily medicationuse, is probably why 36.4% of childrenwith functional constipation use someform of alternative treatment (eg,acupuncture, homeopathy, mind-bodytherapy, musculoskeletal manipula-

tions such as osteopathic and chiro-practic manipulations, and spiritualtherapies such as yoga).6

To date, no systematic reviews of theeffectiveness of nonpharmacologictreatments (fiber, fluid, physical move-ment, prebiotics and probiotics, be-havioral therapy, multidisciplinarytreatment, and forms of alternativemedicine) for childhood constipationhave been published. Furthermore, thepublished guidelines for the treatmentof functional constipation are basedon reviews of the literature that did notapply a systematic literature search,did not incorporate quality assess-ment of studies, or used a languagerestriction.5,7–9 Therefore, it was ouraim to investigate systematically andto summarize the quantity and qualityof all current evidence on the effects offiber, fluid, physical movement, prebi-otics, probiotics, behavioral therapy,multidisciplinary treatment, and alter-native medicine (including acupunc-ture, homeopathy, mind-body therapy,musculoskeletal manipulations suchas osteopathic and chiropractic ma-nipulations, and spiritual therapiessuch as yoga) in the treatment of child-hood constipation.

METHODS

Data Sources

The Embase, Medline, and PsycINFO da-tabases were searched by a clinical li-brarian from inception to January2010. The key words used to describethe study population were “constipa-tion,” “obstipation,” “fecal inconti-nence,” “coprostasis,” “encopresis,”and “soiling.” These words were com-bined with key words referring to thedifferent types of interventions thatwere investigated in the present re-view. Additional strategies for identify-ing studies included searching the ref-erence lists of review articles andincluded studies. No language restric-

tion was applied. The full search strat-egy is available from the authors.

Study Selection, Data Extraction,and Methodologic Quality

Two reviewers (Drs Tabbers and Bo-luyt) independently screened the ab-stracts of all identified published arti-cles for eligibility. Inclusion criteriawere as follows. (1) The study was asystematic review or randomized con-trolled trial (RCT) and contained �10subjects per arm. (2) The study popu-lation consisted of children 0 to 18years of age with functional constipa-tion. (3) A definition of constipationwas provided. (4) The study evaluatedthe effect of a nonpharmacologictreatment, compared with placebo, notreatment, another alternative treat-ment, or medication, for constipation.(5) Nonpharmacologic treatments in-cluded fiber, fluid, physical movement,prebiotics, probiotics, behavioral ther-apy, multidisciplinary treatment, andalternative medicine. (6) Outcomemeasures were either establishmentof normal bowel habits (increase indefecation frequency and/or decreasein fecal incontinence frequency) ortreatment success as defined by theauthors of the study, adverse effects,and costs. All potentially relevant stud-ies were retrieved as full articles. Arti-cles concerning children with organiccauses of constipation and childrenwith exclusively functional, nonreten-tive, fecal incontinence were excluded.Data were extracted by 2 reviewers(Drs Tabbers and Boluyt), who usedstructured data extraction forms. Tworeviewers independently rated themethodologic quality of the includedstudies by using a standardized list de-veloped for RCTs, that is, the Delphi list(Table 1). Disagreements in any of theaforementioned steps were resolvedthrough consensus, when possible, ora third person (Prof Dr Benninga)made the final decision.

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Data Analyses

Methodologic quality scores were cal-culated as a percentage of the maxi-mal quality score on the Delphi list.High quality was defined as a score of�60% (ie, �6 points) and low qualityas a score of�60%.10 Table 1 presentsthe Delphi list.

RESULTS

Study Selection and MethodologicQuality Assessment

We included 9 studies with survey data(collected in 1986–2008) for 640 chil-dren. The sample sizes of the studiesranged from 3111 to 134.12 Table 2 pres-ents the characteristics of the studiesincluded. No RCTs on the effects ofphysical movement, multidisciplinarytreatment, or alternative medicine(acupuncture, homeopathy, mind-bodytherapy, musculoskeletal manipula-tions such as osteopathic and chiro-practic manipulations, or spiritualtherapies such as yoga) for childrenwith constipation were found. All stud-ies were hospital-based; 3 were con-ducted in a general pediatric depart-ment14,18,19 and 6 were conducted in apediatric gastroenterology depart-ment.11–13,15–17 The studies were highlydiverse with regard to the partici-pants, interventions, and outcomemeasures; therefore, a meta-analysis

of all included studies could not be per-formed. Consequently, we discuss allstudies separately, including theirmost important methodologic short-comings. Only 5 studies (56%) hadscores of �6 points, which indicatedgood methodologic quality.

Fiber

Studies Included

One systematic review was found inwhich fiber was one of the optionsevaluated.5 The authors included 2RCTs comparing the effects of fiberversus placebo.11,13 An additionalsearch yielded 1 relevant RCT compar-ing fiber versus lactulose.14 All 3 RCTsare discussed briefly.

Fiber Versus Placebo

A small crossover RCT of low qualitycompared fiber (glucomannan) versusplacebo among children with func-tional constipation.11 The study usedan adequate randomization proce-dure, but no information on blinding ofthe outcome assessor was providedand an intention-to-treat analysis wasnot performed. Other major shortcom-ings that might have caused bias werethe unclear definition of constipationand the unexplained high rate of lossto follow-up monitoring of 32%. Consti-pation was defined as a delay or diffi-

culty in defecation for�2 weeks. If lax-ative therapy was instituted, then allchildren continued to receive the sameamount of laxatives during the study.Patients filled out a daily bowel diary.Physician-rated treatment successwas defined as �3 bowel movementsper week and �1 episode of encopre-sis every 3 weeks, with no abdominalpain. Remarkably, the initial daily fiberintake was low for 71% of all children.Before crossover, the RCT found that theproportion of children with �3 bowelmovements per week and abdominalpain was significantly smaller in the fi-ber group, compared with the placebogroup. The proportion of children whowere rated by their physicians as beingtreated successfully and by their par-ents as experiencing improvement wassignificantly larger after treatment withfiber, compared with placebo.

The second RCT, of high quality, com-pared fiber (a cocoa husk supplement)and placebo among otherwise-healthychildren.13 The study fulfilled most ofthe criteria for validity, such as ade-quate randomization and blinding anda low dropout rate (�20%) distributedequally over the 2 groups. Childrenfilled out a daily diary. The difference inmean basal dietary fiber intake wasnot statistically significant. Moreover,the mean basal dietary fiber intakewas close to the value recommendedfor children (age plus 5 g) in bothgroups (12.3 g/day with fiber and 13.4g/day with placebo; P not reported).13

No significant difference between thegroups in the change in total colontransit time or in the mean defecationfrequency per week was found. Signif-icantly more children (or parents) re-ported a subjective improvement instool consistency but not a subjectiveimprovement in pain during defeca-tion with fiber, compared with pla-cebo. A subanalysis of data for 12 chil-dren with a total basal intestinaltransit time of �50th percentile

TABLE 1 Delphi List

Item No. Question

Study populationD1 Was a method of randomization performed?D2 Was the allocation of treatment concealed?D3 Were the groups similar at baseline regarding the most important prognostic

indicators (age, gender, disease duration, and disease severity)?D4 Were both inclusion and exclusion criteria specified?BlindingD5 Was the outcome assessor blinded?D6 Was the care provider blinded?D7 Was the patient blinded?AnalysisD8 Were point estimates and measures of variability presented for the primary outcome

measures?D9 Did the analysis include an intention-to-treat analysis?D10 Is the withdrawal/drop-out rate�20% and equally distributed?

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TABLE2StudyCharacteristicsofIncludedPediatricStudiesonConstipation

Study

Participants

InterventionvsControl

StudyDuration

OutcomeMeasure

Results

LosstoFollow-up

Monitoring,n/N

(%)

FiberLoening-Baucke

etal11(LQ)

31children,4.5–11.7yofage,with

constipationfor

�6mo,

recruitedfromtertiary

pediatricgastroenterology

clinicinUnitedStates

Glucomannan(fiber),100mg/kg

perdupto5g/d,vsplacebo

(maltodextrins)

4wk

Defecationfrequencyof

�3timesperwk

Abdominalpain

“Improved”(physician

rating)

“Improved”(parentrating)

Intervention:19%;control:52%(P

�.05)


�.05)


�.05)


�.05)

15/46(32)

Castillejoetal13

(HQ)

56children,3–10yofage,with

chronicidiopathicconstipation

accordingtoRomeIIcriteria,

recruitedfromtertiary


clinicinSpain

Cocoahusksupplement(fiber),

10.4g/d(3–6y)or20.8g/d

(7–10y),vsplacebo

4wk

Changeincolonictransit

time

Meandefecationfrequency

No.ofpatientswith

subjectiveimprovement

instoolconsistency

No.ofpatientswith

subjectiveimprovement

inpain

Intervention:61.4hto43.6h;control:

71.5hto61.5h(nosignificance)

Intervention:6.2timesperwk;control:

5.1timesperwk(P

�.78)

Intervention:14;control:6(P

�.039)

Intervention:16;control:11(P

�.109)

Intervention:4/28

(14);control:

4/28(14)

Kokkeetal14

(LQ)


�2of4criteriafor

constipation(�3bowel

movementsperwk,

�2fecal

incontinenceepisodesperwk,

periodicpassageofstoolat

leastonceevery7–30d,or

palpableabdominalorrectal

mass),recruitedfromgeneral

pediatricpracticeclinicin

Netherlands

Fiber(10gin125-mLyogurt

drink)vslactulose(10gin

125-mLyogurtdrink)

8wk

�1fecalincontinence

episodeperwk

Meanabdominalpain

scores

Meanflatulencescores

Necessityofstep-up

medication

Tastescores


�.084)

Week3:intervention:1.58;control:1.43

(P�.33);week8:intervention:1.49;

control:1.39(P

�.50)

Week3:intervention:1.9;control:2.0

(P�.70);week8:intervention:2.0;

control:1.9(P

�.94)

P�.99;absolutenumbersnotreported

P�.657;absolutenumbersnot

reported

Intervention:1/65

(1.5),22/65

(33.8)stopped;

control:2/70

(2.9),11/7

(15.7)stopped

Fluid Youngetal15

(LQ)


scoresof

�8onconstipation

assessmentscale,recruited

frompediatric

gastroenterologydepartment

inUnitedStates

50%waterintakeincrease,

hyperosmolar(�600mOsm/

L)supplementalfluid

treatment,ornormalfluid

intake

3wk

Stoolfrequency

Difficultyinpassingstools

(0�noproblem,1

�someproblem,2

�severeproblem)

Stoolconsistencyscore

50%waterintakeincrease:3.70times

perwk;hyperosmolarfluid:3.44

timesperwk;normalfluidintake:

3.40timesperwk(significancenot

assessed)

50%waterintakeincrease:0.87;

hyperosmolarfluid:0.62;normalfluid

intake:1.06(significancenot

assessed)

50%waterintakeincrease:6.30;

hyperosmolarfluid:5.79;normalfluid

intake:notreported(significancenot

assessed)

?



TABLE2Continued

Study

Participants


StudyDuration

OutcomeMeasure

Results

LosstoFollow-up

Monitoring,n/N

(%)

Prebioticsand

probiotics

Bongersetal16

(HQ)

38children,3–20wkofage,

receiving

�2bottlesofmilk-

basedformulaperdwith

�1of

followingsymptoms:3bowel

movementsperwk,painful

defecation(crying),or

abdominalorrectalpalpable

mass,recruitedfromtertiary


departmentinNetherlands

Newformulawithhigh

concentrationofsn-2palmitic

acid,mixtureofprebiotic

oligosaccharides,and

partiallyhydrolyzedwhey

protein(NutrilonOmneo)vs

standardformula(Nutrilon1)

3wk

Improvementofhardstools

tosoftstools


Intervention:90%;control:

50%(P

�.14)

Intervention:5.6timesperwk;control:

4.9timesperwk(P

�.36)

3wk:3/38(7.9);6

wk:14/38(37)

Banaszkiewicz

etal17(HQ)

84children,2–16yofage.with

�3bowelmovementsperwk

for

�12wk,recruitedfrom


departmentinPoland

LactobacillusGG,109colony-

formingunitstwiceperd,

�70%lactulose,1mL/kgperd,

vsplacebo

�70%lactulose,

1mL/kgperd

12wk


at12wk

Meanfrequencyoffecal

soilingat12wk

Meanfrequencyof

strainingat12wk

Treatmentsuccess(�3

bowelmovementsper

wkwithoutfecalsoiling)

Intervention:6.1timesper

wk;control:6.8times

perwk(P

�.5)

Intervention:0.8episodes

perwk;control:0.3

episodesperwk(P

�.9)


wk;control:1.6times

perwk(P

�.6)

12wk:intervention:72%;control:68%

(P�.9);24wk:intervention:64%;

control:65%(P

�1.0)

Intervention:5/43

(11.6);control:

3/41(7.3)

Buetal18(HQ)


�3bowelmovementsperwk

for

�2moand1ofthe

following:analfissureswith

bleeding,fecalsoiling,or

passageoflargehardstools,

recruitedfromgeneral

pediatricpracticeinTaiwan

Lactobacilluscaseirhamnosus

(N�18),8

�108colony-

formingunitsperd;

magnesiumoxide(control1),

50mg/kgperd(N

�18);or

placebo(control2)(N

�9)

4wk

Meanfrequencyof

abdominalpain

Treatmentsuccess(defined

as�3bowelmovements

perwkwithoutfecal

soilingbyfourthwk)

Meanfrequencyoffecal

soiling

Proportionofhardstools

Frequencyofuseof

lactulose



d;control1:4.8times

perd(P

�.04)

Intervention:78%;control

1:72%(P

�.71)

Intervention:2.1episodes

perwk;control1:2.7

episodesperwk

(significancenot

assessed)

Intervention:22.4%;control

1:23.5%(P

�.89)


wk;control1:5.0times

perwk(significancenot

assessed)

Intervention:0.6timesperd;control1:

0.5timesperd(P

�.77)

4/45(8.8)

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showed that the change in total intes-tinal transit time was significantlygreater with fiber, compared with pla-cebo (�38.1 hours [95% confidence in-terval: �67.9 to �8.4 hours]; P �.015).

Fiber Versus Lactulose

A low-quality RCT compared fiber withlactulose for 8 weeks, followed by 4weeks of weaning, among otherwise-healthy children with constipation.14

The study used an adequate random-ization procedure, but no informationon blinding of the outcome assessorwas provided, no intention-to-treatanalysis was performed, and the drop-out rate was high and not equally dis-tributed. Polyethylene glycol (macro-gol 3350) was added if no clinicalimprovement was observed after 3weeks. The RCT found no significant dif-ference between the groups in thenumbers of children with �1 fecal in-continence episode per week or in themean scores (scale: 0� not at all, 1�sometimes, 2� often, 3� continuous)for people with abdominal pain or flat-ulence at weeks 3 and 8 of follow-upmonitoring. The RCT also found no sig-nificant difference between the groupsin the necessity for step-upmedicationor in taste scores, but absolute num-bers were not reported. All includedRCTs reported no adverse effects offiber.

Fluid

One low-quality RCT that compared 3groups, that is, 50% water intake in-crease, hyperosmolar (�600mOsm/L)supplemental fluid treatment, and nor-mal fluid intake, met our inclusion cri-teria.15 No information was providedabout randomization, blinding, or therate of loss to follow-up monitoring.Furthermore, no statistical assess-ment was conducted, and data werereported incompletely. Similar stoolfrequencies were found at 3 weeks forthe 3 groups, and no differences withTA

BLE2Continued

Study

Participants


StudyDuration

OutcomeMeasure

Results

LosstoFollow-up

Monitoring,n/N

(%)

Behavioral

therapy

Taitzetal19(LQ)47childrenwithfecal

incontinence,withorwithout

constipation,recruitedfrom

generalpediatricdepartment

inUnitedKingdom

Psychotherapyvsbehavior

modificationtechniques

12mo

Cure,improvement,orno

response(seetext)

Cure:n

�22;improvement:n

�8;no

response:n

�16

17/47(36)

vanDijketal12

(HQ)

134childrenwithfunctional

constipation(�2of4criteria:

defecationfrequencyof

�3

timesperwk,fecal

incontinence

�2timesperwk,

passageoflargeamountsof

stoolatleastonceevery7–30

d,orpalpableabdominalor

rectalfecalmass)recruited

fromtertiarypediatric

gastroenterologydepartment

inNetherlands

Behavioraltherapyvs

conventionaltreatment

6mo

Meanfecalincontinence

frequency

Successrate(�3bowel

movementsperwkand

fecalincontinence

frequencyof

�1time

per2wk,irrespectiveof

laxativeuse)


22wk:5vs2.1episodes

perwk;6mo:8.6vs6.4

episodesperwk(P

�.135)

22wk:51.5%vs62.3%(P

�.249);6mo:42.3%vs

57.3%(P

�.095)

22wk:5.4vs7.2timesperwk;6mo:5.3

vs6.6timesperwk(P

�.021)

20/134(14.9)

HQindicateshighquality;LQ,lowquality.



respect to difficulty in passing stoolswere found (significance not as-sessed). Stool consistencies were re-ported only for the water increasegroup and the hyperosmolar fluidgroup and were similar at 3 weeks(significance was not assessed).

Prebiotics

One systematic review was found thatincluded 1 small, high-quality RCT com-paring a standard formula (Nutrilon 1[Nutricia Nederland BV, Zoetermeer,Netherlands]) with a formula with ahigh concentration of sn-2 palmiticacid, a mixture of prebiotic oligosac-charides, and partially hydrolyzedwhey protein (Nutrilon Omneo [Nutri-cia Nederland BV]).5,16 That study ful-filled most of the criteria for validity,such as adequate randomization andblinding, and inclusion and exclusioncriteria were both clearly specified;however, the study was designed orig-inally as a crossover trial but, becauseof the high rate of loss to follow-upmonitoring (37% after 6weeks), the re-sults of the first treatment period onlywere analyzed. No significant differ-ence between the 2 groups in themeandefecation frequency per week after 3weeks was found. A difference in im-provement of hard stools to soft stoolsin favor of the prebiotic group wasfound; however, this difference wasnot statistically significant.

Probiotics

One systematic review was found thatincluded 2 RCTs evaluating the effectsof probiotics.5,17,18 The first high-qualitytrial was conducted to determinewhether Lactobacillus rhamnosus GGwas an effective adjunct to lactulosefor treating constipation in children.The study fulfilled all criteria for valid-ity. Childrenwith constipation received1 mL/kg per day of 70% lactulose plus109 colony-forming units of L rhamno-sus GG or 1 mL/kg per day of 70% lac-tulose plus placebo twice daily for 12

weeks.17 There were no significant dif-ferences in rates of treatment success(defined as �3 bowel movements perweek with no episodes of fecal inconti-nence) at 12 and 24 weeks between theL rhamnosus GG group and the pla-cebo group. No significant differencesbetween the probiotic group and theplacebo group with respect to thenumbers of episodes of fecal soilingper week at 12 weeks, frequencies ofstraining at 12 weeks, and proportionsof children using laxatives at 24 weekswere found.

The second high-quality RCT comparedmagnesium oxide with the probioticLactobacillus casei rhamnosus or pla-cebo.18 The placebo group includedonly 9 patients and therefore is not dis-cussed. The study fulfilled almost allimportant criteria for validity. Similardifferences in defecation frequencieswere found for the probiotic group andthe magnesium oxide group. The clini-cal relevance of these differences indefecation frequencies is unclear. TheRCT also found that probiotics signifi-cantly reduced abdominal pain, com-pared with osmotic laxatives. It foundno significant difference in rates oftreatment success (defined as �3spontaneous defecations per weekwith no episodes of fecal incontinenceby the fourth week) between probiot-ics and osmotic laxatives, comparedwith placebo. The RCT also found simi-lar rates of fecal incontinence (statis-tical significance between groups wasnot assessed). It found no significantdifference in the proportions of hardstools between probiotics and osmoticlaxatives. Both trials did not report anyadverse events for the groups receiv-ing probiotics.

Behavioral Therapy

We found 1 systematic review (searchdate from inception to 2006, including18 RCTs and 1186 children; 17 of the 18RCTs investigated children with func-

tional fecal incontinence and thereforeare not discussed) that compared be-havioral and/or cognitive interven-tions, with or without other treat-ments, for the management of fecalincontinence attributable to organic orfunctional constipation in children.20

An additional search found 42 studies,of which 1 RCT met our inclusioncriteria.12

The systematic review included 1 low-quality RCT that compared behavioralinterventions (education) and a sys-tem of rewards from a pediatricianwith monthly psychotherapy with achild psychiatrist.19 The method of ran-domization was not stated clearly.Blinding in this case was not possiblefor the care provider or the patient.However, no information on whetherthe outcome assessor was blindedwas provided. The analysis did not in-clude an intention-to-treat analysis,and the dropout rate was �20%. Allchildren were seen every 6 weeks forperiods from 3 months to 1 year. Atevery visit with the child psychiatrist,the mother and the child were seenseparately for 15 to 30 minutes. Theauthors did not provide any clear de-tails about this psychotherapy. A totalof 22 children experienced cures (�5bowel movements per week with noepisodes of fecal incontinence perweek and no use of laxatives), 8 chil-dren experienced improvement (�3bowel movements per week with �1episode of fecal incontinence perweek), and 16 did not experience im-provement (�3 bowel movements perweek or �1 episode of fecal inconti-nence per week). However, it was notclear from the study how many chil-dren in each group experienced cures,improvement, or no improvement.

One subsequent high-quality RCT com-pared behavioral therapy by a childpsychologist (learning process to re-duce phobic reactions related to defe-cation, which consisted of 5 sequential

REVIEW ARTICLES




steps, ie, know, dare, can, will, and do)and conventional treatment by a pedi-atric gastroenterologist (education,diary, and toilet training with a rewardsystem) over 22weeks (12 visits).12 Thestudy fulfilled all important criteria forvalidity. Both groups used similar lax-ative therapy. Although statisticallysignificant increases in defecation fre-quency and statistically significant re-ductions in fecal incontinence epi-sodes were found in both groups, nosignificant differences between thegroups in defecation frequencies at 22weeks and 6 months or in episodes offecal incontinence were seen. Further-more, no significant differences be-tween the groups with respect to suc-cess rates were found. After 6 months,the proportion of children with behav-ioral problems was significant smallerin the behavioral therapy group, com-pared with the conventional treatmentgroup (11.7% vs 29.2%; P� .039).

DISCUSSION

This systematic review clearly shows alack of adequately powered, high-quality studies evaluating the thera-peutic role of nonpharmacologic treat-ments. Although the first step oftreatment consists of dietary advice(adequate fiber and fluid intake) andbehavioral interventions, no evidencefrom trials suggesting any effect forfluid supplements or behavioral ther-apy was found. Only marginal evidenceshowing that fiber supplements aremore effective than placebo in the careof children with constipation exists.Also, no evidence was found for prebi-otics or probiotics. Moreover, no RCTsinvolving physical movement, multidis-ciplinary treatment, or alternativemedicine (including acupuncture,homeopathy, mind-body therapy, mus-culoskeletal manipulations such as os-teopathic and chiropractic manipula-tions, and spiritual therapies such asyoga) were found.

The results of the few, mainly under-powered, studies included in this re-view should be interpreted cautiously,given the lack of uniform definitionsused for constipation and the meth-odologic limitations of the publishedstudies. Each included trial used a dif-ferent study design with respect to theduration of the study, the number ofvisits, the method of blinding, the out-come measures, and follow-up moni-toring. Future studies with childrenwith constipation should be conductednot only in tertiary care settings butalso in primary and secondary caresettings, with standardized protocolsas suggested by experts in both adultand pediatric functional gastrointesti-nal disease. With improvements in thequality of research methods, the qual-ity of care should improve through ear-lier and better recognition of constipa-tion and improved diagnostic andtherapeutic strategies. Therefore, in-volved researchers should use homo-geneous patient populations and out-come measures, including standarddefinitions as described in the Rome IIIcriteria.21,22 Because functional consti-pation is a long-lasting problem inmany cases, long-term follow-up mon-itoring is necessary for better under-standing of the clinical course of thedisease.4 Growing up with a chronicdisorder may impede the child’s devel-opment and may affect psychologicaland psychosocial functioning. There-fore, quality-of-life assessments, usingbaseline generic and before/afterdisease-specific quality-of-life instru-ments, are important secondary out-come measures.20

High success rates for placebo (60%)often are reported for pediatric andadult patients with functional gastro-intestinal disorders.23,24 Despite thehigh response rates for placebo, thereis a paucity of placebo-controlled stud-ies with large patient samples for pe-diatric patients with constipation. It is

well known that patients given placebohave expectations of future responses,which influences outcomes. In fact, thereported responses to placebo in RCTsmight point toward the natural courseof disease, fluctuations in symptoms,regression to the mean, or effects ofother simultaneous treatments. There-fore, studies with such children thatinclude groups that receive no treat-ment, to control for natural historyand regression to the mean and tomake the studies more likely to deter-mine a real placebo effect, arenecessary.

Despite the high levels of use of non-pharmacologic treatments, we did notfind any comparative trial evaluatingtheir efficacy in childhood constipa-tion.6 Widespread use of therapiessuch as homeopathy, massage ther-apy, and acupuncture with no evidenceof efficacy emphasizes the vulnerabledisposition of patients, who at timesseek out such treatments because ofinadequate effects achieved with con-ventional treatments and the miscon-ception that complementary medicine(forms of alternative medicine) lacksadverse effects and may not interferewith prescribed medications.6 In addi-tion, use of these interventions iscostly. A study involving adults withfunctional gastrointestinal diseases inthe United States showed that one-third of the patients used some com-plementary or alternative medicine(most used were ginger, massagetherapy, and yoga); the median yearlycost was $200.25

The main unanswered question is whywell-designed trials concerning fre-quently used complementary treat-ments are lacking for one of the mostprevalent, frustrating, long-lasting, pe-diatric gastrointestinal disorders.1,4,6

There are some explanations. Lack offunding may play an important role. Al-though governments and private foun-dations are increasingly investigating



nonpharmacologic treatments, theavailable budgets are still very small,in comparison with the budgets forconventional treatment research.6

Furthermore, blinding patients to theirtreatment arm could be difficult insome nonpharmacologic studies, suchas studies assessing the efficacy ofmassage-based therapies. As in everysystematic review, there is a risk thatnot all relevant studies were included.

To minimize this risk, we performed asensitive literature searchwithout lan-guage restrictions.

CONCLUSIONS

We found only some evidence that fibersupplements were more effective thanplacebo in the care of children withconstipation. This study clearly showsthat there is a lack of well-designedRCTs of high quality concerning non-

pharmacologic treatments for chil-dren with functional constipation.Therefore, we recommend additional,well-designed RCTs of high quality toinvestigate the efficacy, safety, andcost-effectiveness of the differenttreatment forms investigated in thisreview, using homogeneous patientpopulations and outcome measures,including standard definitions as de-scribed in the Rome III criteria.

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DOI: 10.1542/peds.2011-0179; originally published online September 26, 2011; 2011;128;753Pediatrics

Merit M. Tabbers, Nicole Boluyt, Marjolein Y. Berger and Marc A. BenningaNonpharmacologic Treatments for Childhood Constipation: Systematic Review

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