Efficacy of Acupuncture in Children with Nocturnal Enuresis: A Systematic Review and Meta ...

13 Pages·2015·1.45 MB·English

Hindawi Publishing Corporation
Evidence-Based Complementary and Alternative Medicine
Volume 2015, Article ID 320701, 12 pages
http://dx.doi.org/10.1155/2015/320701
Research Article
Efficacy of Acupuncture in Children with Nocturnal
Enuresis: A Systematic Review and Meta-Analysis of
Randomized Controlled Trials
Zheng-taoLv,1WenSong,2JingWu,3JunYang,2TaoWang,2Cai-huaWu,4FangGao,4
Xiao-cuiYuan,4Ji-hongLiu,2andManLi4
1DepartmentofOrthopedics,TongjiHospital,TongjiMedicalCollege,HuazhongUniversityofScienceandTechnology,
Wuhan430030,China
2DepartmentofUrology,TongjiHospital,TongjiMedicalCollege,HuazhongUniversityofScienceandTechnology,
Wuhan430030,China
3KeyLaboratoryofEnvironmentandHealth,MinistryofEducationandDepartmentofEpidemiologyandBiostatistics,
SchoolofPublicHealth,TongjiMedicalCollege,HuazhongUniversityofScienceandTechnology,Wuhan430030,China
4DepartmentofNeurobiology,SchoolofBasicMedicine,TongjiMedicalCollegeofHuazhongUniversityofScienceandTechnology,
Wuhan430030,China
CorrespondenceshouldbeaddressedtoManLi;[email protected]
Received27October2014;Revised30January2015;Accepted31January2015
AcademicEditor:HaifaQiao
Copyright©2015Zheng-taoLvetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,
whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
Background.Nocturnalenuresis(NE)isrecognizedasawidespreadhealthprobleminyoungchildrenandadolescents.Clinical
researches about acupuncture therapy for nocturnal enuresis are increasing, while systematic reviews assessing the efficacy of
acupuncturetherapyarestilllacking.Objective.Thisstudyaimstoassesstheeffectivenessofacupuncturetherapyfornocturnal
enuresis.MaterialsandMethods.Acomprehensiveliteraturesearchof8databaseswasperformeduptoJune2014;randomized
controlledtrialswhichcomparedacupuncturetherapyandplacebotreatmentorpharmacologicaltherapywereidentified.Ameta-
analysiswasconducted.Results.Thisreviewincluded21RCTsandatotalof1590subjects.Theoverallmethodologicalqualities
werelow.Theresultsofmeta-analysisshowedthatacupuncturetherapywasmoreeffectiveforclinicalefficacywhencompared
withplaceboorpharmacologicaltreatment.Adverseeventsassociatedwithacupuncturetherapywerenotdocumented.Conclusion.
Basedonthefindingsofthisstudy,wecautiouslysuggestthatacupuncturetherapycouldimprovetheclinicalefficacy.However,the
beneficialeffectofacupuncturemightbeoverstatedduetolowmethodologicalqualities.RigoroushighqualityRCTsareurgently
needed.
1.Introduction ahigherrisk for psychosocial comorbidity and loss of self-
esteem. Such feelings of humiliation, guilt, and shame are
Nocturnal enuresis (NE) is a worldwide health problem also a reasonable source of heartache to the children and
frequently encountered in childhood and is defined as an their parents. The etiology and underlying physiological
involuntaryvoidingofurineduringsleepwithafrequencyof mechanisms of nocturnal enuresis are multifactorial; three
atleasttwiceaweekinchildren,intheabsenceofcongenital commonly proposed mechanisms to bedwetting include
or acquired defects of the central nervous system [1]. It excessive nocturnal urine production, bladder overactivity,
includesmonosymptomaticnocturnalenuresis(MNE)with andafailuretoawakeninresponsetobladdersensations[3].
no daytime urinary symptoms and nonmonosymptomatic Currentfirst-linenocturnalenuresistherapiescenteron
nocturnalenuresis(NMNE)thatisaccompaniedbydaytime the aforementioned mechanisms; generally accepted treat-
urinary symptoms. Nocturnal enuresis affects 5%–10% of mentsareoralpharmacologicaltherapiesincludingdesmo-
younger school-age children [2]. Enuretic children have pressin, tricyclics, or oxybutynin and behavioral therapies
2 Evidence-BasedComplementaryandAlternativeMedicine
[4].Desmopressinhasbeenwidelyusedforseveraldecades, acupuncture therapy (including needles, moxibustion, acu-
and its reliable therapeutic effect has been proven to one- pressure,electroacupuncture,andacupointinjection,among
third of the unselected enuretic children. But the clinical other techniques), either alone or in conjunction with
effectcannotbemaintainedoncethemedicationisstopped anotherkindofacupuncturetherapy,withoutdifferentiating
and the side effects associated with drugs may cause the different acupuncture therapy techniques, acupoints selec-
patients to be reluctant to use them for long periods. The tion, or needle materials; (4) control group interventions:
preferred behavioral treatment is bed alarm, which needs control interventions included placebo acupuncture or oral
to be continuous and brings the enuretic children different pharmacologicaltreatment;(5)outcomemeasurements:the
degreesofsleepdisordersatthesametime[5]. outcomemeasurementhadtoincludeoverallclinicalefficacy,
Complementary and alternative medicine (CAM) is numberofwetnightsperweek,ormaximumvoidedvolume.
widely advocated to face the increasing demand for non-
pharmacologicalapproaches.AsamainstreamCAMtherapy, 2.3. Exclusion Criteria. Exclusion criteria included the fol-
acupuncture treatment based on TCM theory has been lowing: (1) articles regarding animal experiments, review
commonly used to treat nocturnal enuresis in Chinese articles, case reports, or expert experience reports; (2)
cultures.Comparedtoconventionalcare,itssafetyandcost nonrandomizedstudies;(3)studiesthatcompareddifferent
effectivenessassurethemaintenanceofpatients’compliance. acupuncture modalities or acupoints selection; (4) exper-
Unfortunately,thereislittlepublishedinformationtowarrant imental groups that accepted complex therapy, while the
acupuncture therapy as standard treatment of nocturnal contributing factor could not be distinguished; (5) studies
enuresis.Theaimofthisreviewistoevaluatetheefficacyof thatwereduplicatesforretrievingorpublishing.
acupuncturetherapyinthetreatmentofnocturnalenuresis
when compared with placebo acupunctureor oral pharma-
2.4. Data Extraction. Two reviewers (Zheng-tao Lv and
cological treatment based on randomized controlled trials
Wen Song) reviewed each article independently and were
(RCTs).
blindedtothefindingsoftheotherreviewer.Inaccordance
with the predetermined inclusion criteria, two reviewers
2.MaterialandMethods
independently performed a rigorous screening to identify
qualifiedarticles,andtheyextracteddataindependentlyfrom
2.1. Literature Search Strategy. A comprehensive litera-
these articles using a standardized collection form, which
ture search of the Cochrane Central Register of Con-
includes first author, year of the study, sample size, nation
trolled Trials (CENTRAL), Cochrane Database of Sys-
or region, baseline characteristics, methodological features
tematic Review (CDSR), EMBASE, ISI Web of Science,
of the studies, quality of trial design, interventions, main
and PubMed was conducted. We also searched Chinese
outcome assessments, follow-up time, and withdrawal. If
databases, including China Knowledge Resource Integrated
the required information was not available in the included
database(CNKI),WanFangData,VIP,andChineseBiomed-
studies, we contacted the original authors by email. Any
ical (CBM) Literature database. In addition, we searched
discrepanciesbetweenreviewerswereresolvedthroughdis-
databases that contained registered trials, such as Clinical-
cussion until a consensus was reached. The third review
Trials.gov(http://www.clinicaltrials.gov).Alldatabaseswere
author (Man Li) was consulted if a consensus could not be
searched from their inception dates up to June 2014; lan-
reached.
guageswererestrictedtoChineseandEnglish.Thefollowing
medicalsubjectheadingsorkeywordswereusedforEnglish
databases: enuresis, nocturnal enuresis, nighttime urinary 2.5. Quality of the Studies. The methodological quality of
incontinence,bedwetting,acupuncture,electroacupuncture, the included trials was evaluated using the Jadad quality
auricular acupuncture, ear acupuncture, scalp acupuncture, scale [27]: (1) randomization (the study was described as
acupoint,moxibustion,acupressure,andacustimulation.For randomized),(2)double blinding(participantmaskingand
Chinesedatabasesweusedfreetexttermsas“Zhen”or“Jiu” researchermasking),(3)reportingofthenumberofdropouts
or “Xue Wei” and “Yi Niao.” In addition, the bibliographies andreasonsforwithdrawal,(4)allocationconcealment,and
of relevant systematic reviews and clinical guidelines were (5) generation of random numbers (by using computer,
manually searched. We also searched the gray literature randomnumberstable,shuffledcards,ortossedcoins).RCTs
that included dissertations, letters, government documents, scored1pointforeachareaaddressedinthestudydesignfor
researchreports,conferenceproceedings,andabstractswhen apossiblescorebetween0and5(highestlevelofquality).The
available. The reference section for each study was also quality of all included studies was assessed by two authors
searched. (Zheng-taoLvandWenSong)andthearticleswereclassified
ashighqualityiftheirJadadscore≥4andlowqualityiftheir
2.2. Inclusion Criteria. Inclusion criteria are as follows: (1) Jadad score ≤3. Disagreements regarding methodological
researchsubjects:theenrolledpatientshadtobediagnosed qualitywereresolvedwithdiscussionbetweenreviewers.
with NE and no restrictions on race, age, or sex were
imposed;(2)studydesign:theincludedstudieswererequired 2.6.DataSynthesisandAnalysis. Themeta-analysisandsta-
to be RCTs in Chinese or English aiming to assess the tisticalanalysiswereperformedbyusingRevMan5.1analyses
efficacy of acupuncture therapy for NE; (3) experimental softwareoftheCochraneCollaboration.Weextrapolatedthe
group interventions: experimental group mainly received oddsratio(OR)andtheassociated95%confidenceinterval
Evidence-BasedComplementaryandAlternativeMedicine 3
PubMed=73 CBM=942
Web of Science=108 CNKI=880
n
atio EMBASE=136 WangFang=633
fic Cochrane library=29 VIP=779
nti
e
d
I
Records after duplicates removed
(n=1936)
g
n
ni
e
e
cr
S
Records screened Records excluded
(n=1644) (n = 1583)
Full-text articles assessed Full-text articles excluded,
y for eligibility with reasons (n = 40)
bilit (n = 61) Non-RCT = 17
Eligi Duplicates = 6
Unsuitable intervention = 7
Complex therapy = 6
Studies included in Unsuitable outcome = 4
quantitative synthesis
(n = 21)
d
e
d
u
ncl Studies included in
I
quantitative synthesis
meta-analysis
(n = 19)
Figure1:Flowchartoftheliteraturesearchandstudyselection.
(CI)fortreatmenteffect.Thechi-squaredtestandtheHiggins two different kinds of acupuncture therapy; 4 studies did
𝐼2testwereusedtoassesstheheterogeneityofthedata[28]. notreportthesuitableoutcome.Finally,21studiesmeetour
Wepooleddataacrossstudiesusingrandomeffectmodelsif inclusion criteria [6–26]. Because only two of these studies
statisticalheterogeneityexists;otherwise,afixedeffectmodel [10,17]comparedacupuncturewithplacebotreatment(e.g.,
willbeused.Publicationbiaswasexploredviaafunnel-plot withoutactive laser light but with or withoutskin contact),
analysis.Begg’stestandEgger’stestwereconductedwhenthe wejustusedthemforsystematicreview(Figure1).
numberofincludedstudiesisequaltoorgreaterthan5(Stata
Software, version 12.0). In case of heterogeneity, subgroup 3.2. The Characteristics and Methodological Quality of the
analysiswasconducted. IncludedTrials. Thecharacteristicsofthe21trialsaresum-
marized in Table1. These studies were published between
3.Results 2001 and 2014. Sixteen studies were published in Chinese
and five studies in English. The 21 RCTs included a total of
3.1. Literature Search Results. An initial search of RCTs 1590 patients with nocturnal enuresis: 826 patients in the
yielded 3580 potential literature citations, including 346 acupuncture group (experimental group) and 731 patients
Englishstudiesand3134Chinesestudies,and1936duplicated in the control group. Age of the patients ranges from 3
articlesweredeleted.Afterscreeningtitlesandabstracts,61 to 21 years. Nineteen studies used 2-parallel-arm group
potentiallyrelevantstudieswereselectedandretrievedfora designs [6, 8–12, 14–26] and two used a 3-parallel-arm
full-text assessment. Of the remaining 61 studies, 17 studies groupdesign[7,13].Theexperimentalgroupmainlyreceived
were excluded because they were not RCTs; 6 articles were acupuncture therapy (including needles, moxibustion, acu-
duplicates; 7 studies took unsuitable intervention; 6 studies pressure,electroacupuncture,andacupointinjection,among
accept the complex therapy, for example, combination of other techniques). Among the 21 studies, western medicine
4 Evidence-BasedComplementaryandAlternativeMedicine
Table1:Characteristicsandmethodologicalqualityofincludedstudies.
Samplesize Age(meanor Jadad
Study Studydesign Nation/region Baseline ECapproval
(n1/n2) range) score
Dongetal.,2012 E:8.61(5∼12)years
[6] RCT,parallel2arms 120(60/60) China C:8.57(5∼13)years Adequate Notreported 1
Hongetal.,2011[7] RCT,parallel3arms 99(33/33/33) China 5∼13years Adequate Notreported 2
E:5∼12years
Huietal.,2006[8] RCT,parallel2arms 67(35/32) China C:6∼11years Adequate Notreported 2
Liu,2007[9] RCT,parallel2arms 60(30/30) China 5∼12years Notreported Notreported 1
RCT,parallel2arms
Karamanetal., Prospective, E:8.5±3.2years
2011[10] randomized, 83(57/26) Turkey C:8.9±3.3years Adequate Yes 3
placebocontrolled,
single-blindstudy
Dingetal.,2007 RCT,parallel2arms 80(42/38) China 3∼13years Adequate Notreported 1
[11]
TongandZhan, RCT,parallel2arms 60(30/30) Guinea-Bissau 6∼20years Adequate Notreported 2
2009[12]
Moursyetal.,2014 15.7years(range
RCT,parallel3arms 186(62/62/62) Egypt Adequate Yes 3
[13] 10–21years)
TianandZhong, E:7.58±2.16years
2008[14] RCT,parallel2arms 228(116/112) China C:8.26±2.67years Adequate Notreported 3
LingandChen, E:9.2(5∼16)years
2011[15] RCT,parallel2arms 60(30/30) China C:9.1(5∼15)years Adequate Notreported 2
Radmayretal., E:8.6(5∼16)years
2001[16] RCT,parallel2arms 40(20/20) Austria C:8.0(5∼14)years Adequate Yes 2
RCT,parallel2arms
Prospective,
Radvanskaetal., single-blind, E:8.7±1.4years
2011[17] randomized, 29(16/13) Slovakia C:8.6±1.3years Adequate Yes 4
placebocontrolled
design
Yangetal.,2012 RCT,parallel2arms 69(35/34) China 3∼15years Adequate Notreported 1
[18]
E:8.5±0.1years
Luo,2010[19] RCT,parallel2arms 40(20/20) China C:8.4±0.2years Adequate Notreported 1
Tangetal.,2012 E:5∼11years
[20] RCT,parallel2arms 48(24/24) China C:5∼12years Adequate Notreported 2
Qiu,2008[21] RCT,parallel2arms 56(31/25) China 3∼16years Notreported Notreported 1
Zhuetal.,2003 RCT,parallel2arms 76(41/35) China 4∼15years Adequate Notreported 1
[22]
Zhang,2010[23] RCT,parallel2arms 80(40/40) China 3∼18years Adequate Notreported 1
ChenandGu,2003 RCT,parallel2arms 72(40/32) China 5∼14years Adequate Notreported 1
[24]
Yukseketal.,2003 E:7.67±2.34years
[25] RCT,parallel2arms 24(12/12) Turkey C:7.41±2.67years Adequate No 1
HongandZhang, RCT,parallel2arms 30(15/15) China 8∼21years Adequate Notreported 1
2009[26]
therapy(e.g.,desmopressin,Meclofenoxate)wasusedasthe ThemeanJadadscoreofthese21studieswas1.7,ranging
interventionmethodforthecontrolgroupin9studies[6,8, from1to4points(Table1).Only1of21RCTsmettheJadad
9,11,13,16,22,23,25];traditionalChinesemedicine(TCD) criteriaforhighquality[17].Allofthestudiesincludedsug-
wasusedin10studies[7,12,14,15,18–21,24,26];andplacebo gestedrandomization,and9studiesreportedthemethodof
treatmentorsham-acupuncturewasusedin2studies[10,17]. randomsequencesgeneration[7,8,12–17,20].Inthatstudy,
Themainoutcomeindicatorsreportedintheincludedstudies it was not feasible to blind the participant or the therapist.
werecurerate,improvementrate,andmeanweeklynumber Theoutcomeassessorwasblindedinonlytwostudies[10,17];
ofwetnights;Twostudiesreportedmaximumvoidedvolume we considered that the outcomes and their measurements
(MVV)asoutcomeindicators[13,17](Table2). are likely to be influenced by lack of blinding. Four studies
Evidence-BasedComplementaryandAlternativeMedicine 5
Outcomemeasurement Curerate,improvementrate,follow-upat1and6months Curerate,improvementrate Curerate,totaleffectiverate,follow-upat1month Curerate,improvementrate Completeimprovementrate,partialimprovementrate,meannumberofweeklybedwettingepisodes:thechildrenwerereevaluated15,30,90,and180daysaftertreatment Curerate,improvementrate Curerate,improvementrate Curerate,improvementrate,meanweeklynumberofwetnights,MVV(maximumvoidedvolume):thepatientswereevaluatedonceevery2weeksfor3monthsandonceevery4weeksfor6months Curerate,improvementrate Curerate,improvementrate Responserate,partialresponserate
Curerateofcontrolgroup 36/60(60%) 8/33(24.24%) 14/32(43.8%) 9/30(30%) 3/26(11.5%) 13/38(34.2%) 10/30(33.3%) 35/62(56.5%)46/82(74%) 47/112(41.96%) 15/30(50%) 15/20(75%)
s. p
ofincludedstudie Curerateofinterventiongrou 46/60(76.67%) 20/33(60.6%)19/33(57.6%) 20/35(57.2%) 18/30(60%) 31/57(54.4%) 25/42(59.5%) 17/30(56.7%) 33/62(53%) 61/116(52.59%) 18/30(60%) 13/20(65%)
s
erventionsandoutcome Controltreatment Westernmedicine:𝑛=60Meclofenoxate() Chinesepatent𝑛=33medicine()Westernmedicine:imipramine𝑛=32hydrochloride()Westernmedicine:𝑛=30Meclofenoxate() Placebotherapy:withanonlaserlightsource𝑛=26() Westernmedicine:𝑛=38Meclofenoxate()Chinesepatent𝑛=30medicine()Westernmedicine:𝑛=62desmopressin()Combinationtherapy:acupuncture+𝑛=62desmopressin()Chinesepatent𝑛=112medicine()Chinesepatent𝑛=30medicine()Westernmedicine:𝑛=20desmopressin()
nt
Table2:I ExperimentaltreatmentAcupointinjectionwithscrapingtherapy𝑛=60()𝑛=33Moxibustion()𝑛=33Acupuncture() Heat-producing𝑛=35needling() Enuresispatch𝑛=30() Laseracupuncture𝑛=57() Enuresispatch𝑛=42()Suspended𝑛=30moxibustion() Laseracupuncture𝑛=62() Acupuncture𝑛=116()Acupointinjection𝑛=30()LaserAcupuncture𝑛=20()
nt d d d d d d
Follow-upftertreatme 6months Notreporte 1year Notreporte 6months 3months Notreporte 6months Notreporte Notreporte Notreporte
a
onofment eks nth nth eks eks nth nth nths eks nth nths
Duratitreat 5we 1mo 1mo 3we 4we 1mo 1mo 3mo 2we 1mo 6mo
Study Dongetal.,2012[6] Hongetal.,2011[7] Huietal.,2006[8] Liu,2007[9] Karamanetal.,2011[10] Dingetal.,2007[11]TongandZhan,2009[12] Moursyetal.,2014[13] TianandZhong,2008[14]LingandChen,2011[15]Radmayretal.,2001[16]
6 Evidence-BasedComplementaryandAlternativeMedicine
d
s n
ht a
Outcomemeasurement Wetnights/wk,voidingfrequency,nocturnalurineproductiononwetnigMVV(maximalvoidedvolume),AVV(averagevoidedvolume) Curerate,improvementrate Curerate,improvementrate Curerate,improvementrate Curerate,improvementrate Curerate,improvementrate Curerate,improvementrate Curerate,improvementrate Completeimprovementrate,partialimprovementrate,follow-upat15days1,3,and6months Curerate,improvementrate
Curerateofcontrolgroup notreported 12/34(35.3%) 4/20(20%) 11/24(45.8%) 15/25(60%) 6/35(17.1%) 6/40(15%) 14/32(43.7%) 7/12(58.3%) 5/15(33.3%)
p
u
Curerateofnterventiongro Notreported 21/35(60%) 14/20(70%) 16/24(66.7%) 17/31(54.8%) 19/41(46.5%) 22/40(55%) 36/40(90%) 10/12(83.3%) 13/15(86.7%)
d. i
e
Table2:Continu Controltreatment Placebotherapy:withoutactivelaserlightbutwithorwithoutskincontact𝑛=13() Chinesepatent𝑛=34medicine() Chinesemedicine𝑛=20() Chinesemedicine𝑛=24()Chinesemedicine𝑛=25()Westernmedicine:𝑛=35Meclofenoxate() Westernmedicine:𝑛=40desmopressin() Chinesemedicine𝑛=32() Westernmedicine:𝑛=12oxybutynin() Chinesemedicine𝑛=15()
Experimentaltreatment Laseracupuncture𝑛=16() Earpointtappingwithmedicinalcake-separated𝑛=35moxibustion()Acupuncture-massage𝑛=20() 𝑛=24Massage() Earpointtapping𝑛=31()Acupointinjection𝑛=41()Medicinalcake-separatedmoxibustionwithembeddedneedling𝑛=40()Acupointinjection𝑛=40() 𝑛=12Acupressure() Needlewarming𝑛=15moxibustion()
nt d d d d d d d d
Follow-upftertreatme Notreporte Notreporte Notreporte 1month Notreporte 3months Notreporte Notreporte Notreporte Notreporte
a
onofment eks nth nths eks nth eks nth eks nths nth
Duratitreat 5we 1mo 3mo 2we 1mo 3we 1mo 2we 6mo 1mo
3
Study Radvanskaetal.,2011[17] Yangetal.,2012[18] Luo,2010[19] Tangetal.,2012[20] Qiu,2008[21] Zhuetal.,2003[22] Zhang,2010[23] ChenandGu,200[24] Yukseketal.,2003[25] HongandZhang,2009[26]
Evidence-BasedComplementaryandAlternativeMedicine 7
reported complete follow-up of all subjects [10, 13, 14, 17]. respectively. The pooled data showed significant difference
All the studies presented selective reporting, characterized betweenacupuncturetherapyandMeclofenoxate(OR=2.81;
similarity of baseline. In general, the methodological and 95%CI,1.62–3.96;𝑃<0.0001),withnoobviousheterogene-
reportqualitiesoftheincludedstudieswerepoor. ity(Figure3).Thepooledeffectsofthreeindependenttrials
suggested that there was no significant difference between
3.3. Meta-Analysis Results. The 21 included RCTs adopted desmopressin and acupuncture in treating NE (OR = 1.57;
inconsistentinterventionsanddifferentreportedoutcomes, 95%CI,0.38–6.57;𝑃 = 0.54)(Figure4).Sinceonlyonetrial
with no unified efficacy standard. To reach a consistent utilized imipramine hydrochloride as medicine control and
understandingofthetherapeuticeffectofacupuncturether- only one trial utilized oxybutynin, results from these two
apyfornocturnalenuresis,interventiontherapiesforcontrol studiesarepresentedasnarrativedescription.Therewasno
group were further refined. We limited the control group significantdifferencebetweenimipraminehydrochlorideand
methods to western or traditional Chinese medicine alone, acupuncturetherapy(OR=1.71;95%CI,0.65–4.51;𝑃=0.27).
astwostudiesusedplacebotreatmentorsham-acupuncture Comparedwithoxybutynin,acupuncturecouldnotfurther
ascontrolgroup[10,17]andoneofthesetwostudiesdidnot improvetheclinicaleffect(OR=3.57;95%CI,0.53–2;𝑃 =
reportthecurerateaseffectiveoutcomes[17].Furthermore, 0.54).
the definition of cure rate was consistent among the other
included 19 studies; we conducted the meta-analysis to 3.5. Acupuncture Therapy versus Placebo Treatment. Two
comparetheoverallcureratedeterminedinthesestudies. studies used placebo treatment or sham-acupuncture as
Threestudiesreportedmeanweeklynumberofwetnights control group [10, 17]. However, results of these two stud-
[10,13,17]andtwostudiesreportedmaximumvoidedvolume ies were inconsistent. Radvanska et al. [17] compared the
(MVV)[13,17]astheeffectiveoutcomes,consideringthelack treatment efficacy of laser acupuncture therapy with sham-
ofadequatenumbersofstudies;theseresultswillbepresented acupuncture;they foundno significant effect ofactive laser
inthefollowingpartofourreview. acupuncture on maximal voided volume (first morning
Theresultsofheterogeneitytestsindicatedthat𝐼2 >50% void excluded), maximal morning voided volume, voiding
and 𝑃 < 0.1 for the 19 included studies [6–9, 11–16, 18– frequency,enuresisfrequencybeforeandaftertreatment,or
26] and that the overall heterogeneity existed (𝑃 = 0.002, nocturnalurineproductionamongthepatientgroups,butit
𝐼2 = 54%).Therefore,arandomeffectsmodelwasused.The resulted in a significant increase in average daytime voided
combinedeffectsof19independenttrialresultsshowedthat volume. There was no effect of skin contact during placebo
acupuncture therapy had further improved the cure rate in laseracupuncture.Radvanskaetal.[17]concludedthatlaser
patientswithnocturnalenuresiswhencomparedwithcontrol acupuncturehadsubtleeffectsonbladderreservoirfunction;
groupacceptingmedicinetherapy(OR=2.58;95%CI,1.84– however,itisaninefficienttreatmentformonosymptomatic
3.61;𝑃<0.0001)(Figure2). nocturnal enuresis with reduced maximal voided volume.
Karamanetal.[10]evaluatedtheeffectoflaseracupuncture
3.3.1. Acupuncture versus Western Medicine. Our meta- therapy on patients with primary monosymptomatic noc-
analysis of ten studies [6, 8, 9, 11, 13, 16, 22, 23, 25], which turnal enuresis. The mean number of bedwetting episodes
compared acupuncture therapy with traditional Chinese was1.7perweek6monthsafterlasertherapyand3.1inthe
medicine,yieldedencouragingeffectsinfavorofacupuncture placebo group. Laser acupuncture therapy was significantly
therapyonnocturnalenuresis(OR=2.16;95%CI,1.31–3.55; more beneficial compared to placebo in terms of complete
𝑃 < 0.01).Heterogeneitybetweenstudiesexisted(𝑃 = 0.03; dryness, partial improvement, and decrease in the mean
𝐼2 =54%)(Figure2). numberofweeklybedwettingepisodes.
3.6.OtherOutcomes
3.3.2.AcupunctureversusTraditionalChineseMedicine. The
samefindingsappliedtoothertenstudies[7,12,14,15,18–21,
3.6.1. Mean Weekly Number of Wet Nights. Three studies
24,26],whichcomparedacupuncturetherapywithwestern
reported mean weekly number of wet nights [10, 13, 17].
medicine,yieldedencouragingeffectsinfavorofacupuncture
Moursy et al. [13] reported that the difference of reducing
therapyonnocturnalenuresis(OR=3.03;95%CI,1.88–4.88;
the mean weekly number of wet nights in laser acupunc-
𝑃 < 0.01).Heterogeneitybetweenstudiesexisted(𝑃 = 0.01;
ture group, desmopressin group, and combination of laser
𝐼2 =56%)(Figure2).
acupuncture and desmopressin group had no statistical
significance(𝑃 > 0.05).Radvanskaetal.[17]foundthatthe
3.4.SubgroupAnalyses. Asubgroupanalysiswasconducted differenceinthereductionofwetnightswasnotstatistically
tofurtherevaluatetheclinicaleffectofacupuncturetherapy significant between laser acupuncture group and placebo
and identify the heterogeneity within western medicine group. Karaman et al. [10] showed that laser acupunc-
group. The western medicine group was divided into four ture therapy was significantly more beneficial compared to
groupsaccordingtothemedicationtypes.Fourstudiesused placebointermsofadecreaseinthemeannumberofweekly
Meclofenoxate as control intervention [6, 9, 11, 22], three bedwettingepisodesaspreviouslymentioned.
studies used desmopressin as medicine control [13, 16, 23],
and the remaining two studies [8, 25] treated nocturnal 3.6.2. Maximum Voided Volume (MVV). Two studies
children with imipramine hydrochloride and oxybutynin, reported maximum voided volume (MVV) [13, 17] as
8 Evidence-BasedComplementaryandAlternativeMedicine
Experimental Control Odds ratio Odds ratio
Study or subgroup
Events Total Events Total Weight M-H, random, 95% CI Year M-H, random, 95% CI
1.1.1 Acupuncture therapy versus TCM
Chen and Gu, 2003 36 40 14 32 4.2% 11.57 [3.33, 40.27] 2002
Tian and Zhong, 2008 61 120 47 120 8.1% 1.61 [0.96, 2.68] 2008
Qiu, 2008 17 31 15 25 5.0% 0.81 [0.28, 2.36] 2008
Tong and Zhan, 2009 17 30 10 30 5.1% 2.62 [0.92, 7.46] 2009
Hong and Zhang, 2009 13 15 5 15 2.5% 13.00 [2.07, 81.48] 2009
Luo, 2010 14 20 4 20 3.5% 9.33 [2.18, 39.96] 2010
Hong et al., 2011 19 33 8 33 5.1% 4.24 [1.48, 12.17] 2011
Ling and Chen, 2011 18 30 15 30 5.2% 1.50 [0.54, 4.17] 2011
Hong et al., 2011 20 33 8 33 5.0% 4.81 [1.67, 13.86] 2011
Yang et al., 2012 21 35 12 34 5.4% 2.75 [1.04, 7.30] 2012
Tang et al., 2012 16 24 11 24 4.5% 2.36 [0.73, 7.60] 2012
Subtotal (95% CI) 411 396 53.8% 3.03 [1.88, 4.88]
Total events 252 149
Heterogeneity:𝜏2=0.34;𝜒2=22.66, df=10(P=0.01);I2=56%
Test for overall effect:Z=4.55(P<0.00001)
1.1.2 Acupuncture therapy versus western medicine
Radmayr et al., 2001 13 20 15 20 3.8% 0.62 [0.16, 2.43] 2001
Zhu et al., 2003 19 41 6 35 5.0% 4.17 [1.43, 12.20] 2003
Yuksek et al., 2003 10 12 7 12 2.4% 3.57 [0.53, 23.95] 2003
Hui et al., 2006 20 35 14 32 5.5% 1.71 [0.65, 4.51] 2006
Liu, 2007 18 30 9 30 5.0% 3.50 [1.20, 10.20] 2007
Ding et al., 2007 25 42 13 38 5.8% 2.83 [1.14, 7.03] 2007
Zhang, 2010 22 40 6 40 5.0% 6.93 [2.38, 20.16] 2010
Dong et al., 2012 33 60 26 60 6.9% 1.60 [0.78, 3.29] 2012
Moursy et al., 2014 33 62 35 62 6.9% 0.88 [0.43, 1.78] 2014
Subtotal (95% CI) 342 329 46.2% 2.16 [1.31, 3.55]
Total events 193 131
Heterogeneity:𝜏2=0.30;𝜒2=17.47, df=8(P=0.03);I2=54%
Test for overall effect:Z=3.03(P=0.002)
Total (95% CI) 753 725 100.0% 2.58 [1.84, 3.61]
Total events 445 280
Heterogeneity:𝜏2=0.30;𝜒2=41.28, df=19(P=0.002);I2=54%
0.001 0.1 1 10 1000
Test for overall effect:Z=5.50(P<0.00001)
Favouring medication Favouring acupuncture
Test for subgroup differences:𝜒2=0.93, df=1(P=0.34),I2=0%
Figure2:Forestplotofcomparison:theclinicaleffectiverate.
the effective outcomes. Moursy et al. [13] found that it associatedwithEgger’stestwas0.002.Theresultinggraphwas
significantly increased only in laser acupuncture group and asymmetrical,suggesting thepossibilityofpublicationbias,
combination of laser acupuncture and desmopressin group whichwasinlinewithresultsofBegg’stestandEgger’stest
comparing with pretreatment values and desmopressin (Figure5).Inaddition,languagebiasmayexistbecausemost
group, respectively. Thus, bladder capacity significantly ofincludedstudieswerepublishedinChinese.
increased only in patients receiving laser acupuncture
treatment. However, Radvanska et al. [17] reported that the 4.Discussion
MVV had no difference between laser acupuncture group
andplacebogroup. 4.1. Summary of Evidence. The present study analyzed data
from 21 RCTs involving 1590 individuals that featured to
3.7. Publication Bias Analysis. We conducted a funnel plot assesstheefficacyofacupuncturetherapytotreatNE.Based
analysisoftheaforementioned19studies[6–9,11–16,18–26]. onthefindingsinoursystematicreviewandmeta-analysis,
𝑃 value associated with Begg’s test was 0.009 and 𝑃 value acupuncture therapy can significantly improve the clinical
Evidence-BasedComplementaryandAlternativeMedicine 9
Experimental Control Odds ratio Odds ratio
Study or subgroup
Events Total Events Total Weight M-H, fixed, 95% CI Year M-H, fixed, 95% CI
Zhu et al., 2003 19 41 6 35 14.3% 4.17 [1.43, 12.20] 2003
Liu, 2007 18 30 9 30 14.8% 3.50 [1.20, 10.20] 2007
Ding et al., 2007 25 42 13 38 22.7% 2.83 [1.14, 7.03] 2007
Dong et al., 2012 33 60 26 60 48.2% 1.60 [0.78, 3.29] 2012
Total (95% CI) 173 163 100.0% 2.53 [1.62, 3.96]
Total events 95 54
Heterogeneity:𝜒2=2.81, df=3(P=0.42);I2=0%
0.01 0.1 1 10 100
Test for overall effect:Z=4.06(P<0.0001)
Favouring Meclofenoxate Favouring acupuncture
Figure3:Subgroupanalysis:acupuncturetherapyversusMeclofenoxate.
Experimental Control
Study or subgroup Odds ratio Odds ratio
Events Total Events Total Weight M-H, random, 95% CI Year M-H, random, 95% CI
Radmayr et al., 2001 13 20 15 20 29.7% 0.62 [0.16, 2.43] 2001
Zhang, 2010 22 40 6 40 33.2% 6.93 [2.38, 20.16] 2010
Moursy et al., 2014 33 62 35 62 37.1% 0.88 [0.43, 1.78] 2014
Total (95% CI) 122 122 100.0% 1.57 [0.38, 6.57]
Total events 68 56
Heterogeneity:𝜏2=1.31;𝜒2=11.68, df=2(P=0.003);I2=83%
0.01 0.1 1 10 100
Test for overall effect:Z=0.62(P=0.54)
Favouring desmopressin Favouring acupuncture
Figure4:Subgroupanalysis:acupuncturetherapyversusdesmopressin.
0 4.2.MechanismofAcupunctureTherapy. Thepathogenesisof
nocturnal enuresis is multifactorial; several factors such as
0.2 psychosocial,developmental,hormonal,andgeneticfactors
have been proven to be involved in nocturnal enuresis.
R]) 0.4 Nocturnalpolyuria,nocturnaldetrusoroveractivity,andhigh
O arousal thresholds are main pathogenesis of NE. To date,
g[
o increasing evidence suggests that all three mechanisms can
SE(l 0.6 beattributedtobrainstemdisturbance.Thelocuscoeruleus
(LC) has axonal connections with the hypothalamic cells
0.8
thatproducevasopressinandalsoplaysanimportantrolein
arousalfromsleep[29,30].Pontinemicturitioncentercoor-
1 dinatesthemicturitionreflexandoverlapsbothfunctionally
0.001 0.1 1 10 1000
and anatomically with LC. A disturbance in this region of
OR
brainstemmaycausearangeofpathologicalchangeswhich
Subgroups mayresultinthepathogenesisofNE.
Acupuncture therapy versus TCM
Acupuncture points were selected in order to influence
Acupuncture therapy versus western medicine
thespinalmicturitioncentersaswellastheparasympathetic
Figure5:Funnelplotofrandomizedcontrolledtrials. innervation to the urinary tract [31]. With acupuncture
stimulation, levels of enkephalins and endogenous opioids
are increased in both plasma and central nervous system.
efficacy in enuretic children when compared with placebo An increased beta-endorphin level in human cerebrospinal
acupuncture or TCM. In contrast to western medicine, fluid could be detected after acupuncture stimulation [32].
acupuncturetherapywasmoreeffectivethanMeclofenoxate. Andbeta-endorphinwasfoundtobeabletodepressbladder
Conclusions regarding the safety of acupuncture therapy contractions [33]. The therapeutic effects of acupuncture
cannotbedrawnduetothepaucityofevidenceprovidedby therapy can be achieved through the suppression of spinal
theincludedtrials.However,thedrawnconclusionshouldbe and supraspinal reflexes which lead to bladder contraction.
interpretedcautiouslyowingtolowmethodologicalqualities And the clinical efficacy of acupuncture was reflected in
ofincludedstudies. increase in maximum bladder capacity and suppression of
10 Evidence-BasedComplementaryandAlternativeMedicine
detrusor muscle activity; these functional changes might terms, cure rate, complete improvement rate, and response
contributetotheimprovementofNE. rate,aresynonyms;childrenhavingnobedwettingepisodes
In TCM theory, the generation and discharge of urine on follow-ups were defined to be cured. The majority of
are associated with lung, kidney, spleen, and bladder. The oureligiblestudiesfailedtodistinguishbetweenNMNEand
pathogenesis of nocturnalenuresis is Qi deficiency of lung, MNE,makingitdifficulttogetapreciseconclusion.Toour
spleen, and kidney; bladder is not controlled by Qi as well. knowledge, there is still no worldwide unified evaluation
Through different forms of stimulation on meridian points standardtoassessthebasicstateanddisease’sprogressionof
orspecificpartsofbody,imbalanceandinstabilitybetween enuretic children. In addition, the duration of acupuncture
ZangfuorgansarecorrectedtoimprovesymptomsofNEand sessions and follow-ups after treatments vary from studies
maintainthestabilityofinnerstate[34].Basedontheclassical to studies. Since acupuncture therapy has a long-lasting
prescriptions of acupuncture, series of novel acupuncture beneficial effect on enuretic children, the outcomes were
modalities have been widely applied in clinic. In our sys- supposed to be measured at the end of follow-ups after
tematicreview,thespecificinterventionsemployedinthese treatment.
eligible trials included traditional fine needle acupuncture, The utilization of different acupuncture techniques by
moxibustion, electroacupuncture, auricular point sticking, different investigator can greatly affect curative effect of
acupointcatgutembedding,acupressure,transdermaldrugs acupuncturetherapy[5].BasedonTCMtheory,allacupunc-
delivery systems, and acupoint injection. These techniques tureproceduresneedtobeperformedaccordingtosyndrome
were considered as one type of therapy, without differen- differentiation.AlackofunderstandingofTCMwasreflected
tiating acupoint selection or acupuncture forms. Therefore, in the treatment models; treatment following the same
thefindingsinthisreviewmightindicateanoverallefficacy pattern can reduce the therapeutic effect to some extent.
trend,butdefinitiveconclusionscouldnotbedrawn. Acupuncturesessionsshouldbeperformedbaseduponstrict
diagnosis made by four basic diagnostic methods (inspec-
4.3. Comparison with Other Studies. In 2005, a system- tion,auscultation,olfaction,andpalpation)[38].Asvarious
atic review reported that acupuncture in combination with acupuncturemodalitiesaredifficulttomaster,practitioners
anothertherapycouldfurthersignificantlyreducethenum- and physicians are required to have a deep understanding
ber of wet nights when compared to acupuncture therapy of the mechanisms underlying NE so that acupuncture
alone,and,regardingthecomparisonofacupuncturetherapy techniquescouldbeappliedappropriately.Theinvestigators
with antidiuretic medication, the results showed that the who lack universal knowledge of TCM theory should be
outcomefavoredmedicationbutwasnotsignificantlybetter encouragedtoparticipateinthestandardizedtrainingbefore
thanacupuncturetherapy[35].Ourmeta-analysismanaged theapplicationofacupuncture.
to summarize all published RCTs to compare the clinical In contrast to TCM, acupuncture therapy could further
efficacyofacupuncturetherapywithpharmacologicaltreat- improve the clinical effect in treating nocturnal children;
mentorplacebotreatment.Thefindingsinourmeta-analysis no subgroup analysis was made in this group because the
suggestedthatacupuncturetherapywasmoreeffectivethan acupuncture modalities and Chinese medicine types varied
both western diuretic medication and traditional Chinese fromstudiestostudies.Thedataextractedfromthesestud-
medicine,whichrancountertotheconclusioninaforemen- ies suggested an overall efficacy trend; the standardization
tionedsystematicreview. of acupuncture techniques is one problem to be solved
in need. In the subgroup analysis conducted in western
4.4.Limitations. Basedonthestudiesincludedinourmeta- medicine group, acupuncture therapy was more effective
analysis, the methodological qualities were judged to be thanMeclofenoxatewhilenosignificantdifferencecouldbe
generally poor, which might limit the value of conclusions detected between acupuncture and imipramine hydrochlo-
about clinical efficacy of acupuncture therapy for treating ride, desmopressin, or oxybutynin. Types and doses of
NE.Thevastmajorityoftheincludedtrialsfailedtodescribe administered drugs might affect the results of experiment
detailed information about randomization and allocation to a certain extent. Given that the evidence from China
concealment.LackofblindingproceduresinRCTscanalso occupies a large proportion, further rigorous experiments
exaggeratetheconclusionsofthesetrials.Furtherassessment within western context are required. Considering all these
of acupuncture therapy needs to be taken by large-scale above factors, the appearance of heterogeneity could be
clinicalstudieswhichemployrigorousmethodologies. reasonablyexplained.
The diagnosis and therapeutic evaluation standards
employedbystudies,thatareperformedinChina,aremainly 4.5. Suggestion for Future Research. The included studies
inaccordancewith“StandardsforDiagnosisofSyndromesor in our systematic review comprise various methodolog-
Diseases of TCM and Evaluation of the Therapeutic Effect” ical deficiencies, and the findings of the present review
issuedbytheStateAdministrationofTCMin1994[36].In are somewhat limited due to low methodological qualities.
the studies published in English, the majority of recruited Futurerandomizedcontrolledtrialsshouldemployimproved
patientsarediagnosedandevaluatedaccordingtothe“Stan- methodologies and reporting specifications as follows: (1)
dardizationandDefinitionofLowerUrinaryTractDysfunc- all clinical studies of acupuncture should be registered and
tioninChildren”oftheInternationalChildren’sContinence complywiththerevisedstandardsforreportinginterventions
Society(ICCS)[37].Toconductameta-analysis,theoutcome in clinical trials of acupuncture (STRICTA) [39]; (2) the
measureadoptedinincludedRCTswasclinicalefficacy.Such sample sizes should be calculated; (3) the generation of