Grommets for Otitis Media With Effusion in ChildrenWith Cleft Palate: A Systematic Review

abstractBACKGROUND AND OBJECTIVE: No consensus has yet been reachedwith regard to the link between otitis media with effusion (OME), hear-ing loss, and language development in children with cleft palate. Theobjective of this study was to address the effectiveness of ventilationtube insertion (VTI) for OME in children with cleft palate.

METHODS: A dual review process was used to assess eligible studiesdrawn from PubMed, Medline via Ovid, Cumulative Index to Nursing andAllied Health Literature, Cochrane Library, and reference lists between1948 and November 2013. Potentially relevant papers were selectedaccording to the full text of the articles. Relevant data were extractedonto a data extraction sheet.

RESULTS: Nine high- or moderate-quality cohort studies were includedin this study. VTI was administered in 38% to 53% of the OME cases, andmore severe cases appeared more likely to undergo VTI. Comparedwith conservative forms of management (eg, watchful waiting), VTIhas been shown to be beneficial to the recovery of hearing inchildren with cleft palate and OME. A growing body of evidencedemonstrates the benefits of VTI in the development of speech andlanguage in children with cleft palate and OME. These children facea higher risk of complications than those undergoing conservativetreatments, the most common of which are eardrum retraction andtympanosclerosis, with an incidence of ∼11% to 37%.

CONCLUSIONS: This review provides evidence-based informationrelated to the selection of treatment for OME in children with cleftpalate. Additional randomized controlled trials are required to obtainbias-resistant evidence capable of reliably guiding treatment decisions.The conclusions in this review are based on underpowered cohortstudies and very-low-strength evidence. Pediatrics 2014;134:983–994

AUTHORS: Chin-Lung Kuo, MD,a,b,c,d,e Yuan-Heng Tsao, MD,d,e

Hao-Min Cheng, MD, PhD,f,g Chiang-Feng Lien, MD,a,b

Chyong-Hsin Hsu, MD,h Chii-Yuan Huang, MD, PhD,a,b andAn-Suey Shiao, MDa,b,e

Departments of aOtolaryngology–Head and Neck Surgery, andfMedical Research and Education, Taipei Veterans GeneralHospital, Taipei, Taiwan, Republic of China; bDepartment ofOtolaryngology, cInstitute of Brain Science, and gCardiovascularResearch Center, National Yang-Ming University School ofMedicine, Taipei, Taiwan, Republic of China; dDepartment ofOtolaryngology, Taoyuan Armed Forces General Hospital, Taoyuan,Taiwan, Republic of China; eDepartment of Otolaryngology,National Defense Medical Center, Taipei, Taiwan, Republic ofChina; and hDepartment of Pediatrics, Mackay Memorial Hospital,Taipei, Taiwan, Republic of China

KEY WORDScleft lip and palate, conductive hearing loss, grommet tube,middle ear effusion, otitis media, systematic review

ABBREVIATIONSGRADE—Grading of Recommendations Assessment, Developmentand EvaluationOME—otitis media with effusionVTI—ventilation tube insertion

Dr Kuo contributed to the conception and design of thisresearch and the acquisition, analysis, and interpretation ofdata, drafted the first version of the manuscript, andparticipated in a critical revision of the manuscript; Dr Tsaocontributed to the conception and design of the research andthe acquisition, analysis, and interpretation of data andparticipated in revising the manuscript; Dr Cheng participatedin the conception and design of the research and the analysisand interpretation of data and approved revisions to themanuscript; Drs Lien, Hsu, and Huang participated in theconception and design of the research, analysis andinterpretation of data, and revision of the manuscript; Dr Shiaocontributed to the conception and design of the research,acquisition, analysis, and interpretation of data and participatedin critical revisions of the manuscript; and all authors approvedthe final manuscript as submitted.

www.pediatrics.org/cgi/doi/10.1542/peds.2014-0323

doi:10.1542/peds.2014-0323

Accepted for publication Aug 5, 2014

Address correspondence to An-Suey Shiao, MD, and Chin-LungKuo, MD, Department of Otolaryngology–Head and Neck Surgery,Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Rd,Taipei 112, Taiwan, ROC. E-mail: asshiao@gmail.com (A.-S. Shiao);drkuochinlung@gmail.com (C.-L. Kuo)

(Continued on last page)

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Otitis media with effusion (OME) is acollection of nonpurulent fluid in themiddle ear space. Before the age of1year,OMEoccursat leastonce in#90%of children with cleft palate,1 increasingto 97% by the age of 2 years.2 OME maylead to conductive hearing loss of#30dB.3 Long-term hearing loss has beenshown to negatively influence the lan-guage development of children.4–6

Alt7 first identified the association be-tween cleft palate and hearing impair-ment in 1878. Since that time, OME hasbeen the subject of extensive investigation,particularly with regard to children withcleft palate. The long-term benefits ofventilation tube insertion (VTI) remain anissue of debate among specialists, giventhe difficulties and complications inherentin aggressive treatment regimens. Therisks children with cleft palate face inlater life should not be used to justifyearly aggressive treatment of OME untilthe question of optimal managementhas been resolved. Although a largenumber of reviews on the use of surgi-cal treatment for OME in children withcleft palate have been published, manyof these were narrative,3,8–11 and otherswere systematic investigations thatpertained mainly to otherwise healthychildren with typical developmentalcharacteristics.6,12–21 A lack of researchon the subgroup of children with cleftpalate means that there is currently noevidence-based information available toclinicians and parents about the effec-tiveness of grommet insertion to treatOME in children with cleft palate. Only 1systematic review addressed the earlyroutine insertion of grommets for OMEin childrenwith cleft palate.1 In that study,data synthesis was not performedaccording to patient-centered outcomes,and data were limited to studies con-ducted before 2006, since which timea number of important studies havebeen conducted. We therefore concludethat the information currently availableis insufficient to provide a reliable base

with which to evaluate the clinical prac-tice of early routine grommet placementfor OME in children with cleft palate.

This systematic review investigates thebenefits and harm attributable to theplacement of grommets to treat OMEin children with cleft palate. We alsocontrast this invasive formof interventionwith more conservative treatments, in-cluding watchful waiting and the use ofhearing aids.

METHODS

Eligibility Criteria

This study followed the methods usedin Preferred Reporting Items for Sys-tematic Reviews and Meta-Analyses.22

Eligibility criteria were specified un-ambiguously to ensure that studieswere selected in a systematic and un-biased manner. We included case seriesstudies, prospective and retrospectivecohort studies, and randomized con-trolled trials. The patient population wasdefined as children (#18 years old) di-agnosed with any type of cleft palate,including unilateral or bilateral cleftpalate with or without cleft lip, cleftpalate only, and submucous cleft palate.A search was conducted to identifystudies that evaluated the outcomes ofgrommet insertion in children with cleftpalate. We also sought to determinewhether a control group was includedin the studies. Studies had to include$1 outcome of routine or early grom-met insertion related to hearing, speechand language development, frequencyof treatment, and complications orsequelae.

Information Sources

We identified studies by searching elec-tronic databases and then consultingwith experts in the field. The searchwas performed in multiple databasesincluding PubMed (1950 to November2013),MedlineviaOvid(1948toNovember2013), the Cochrane Library (1953 toNovember 2013), and the Cumulative

Index to Nursing and Allied Health Lit-erature (1982 to November 2013). Initialsearches performed in November andDecember2012wereupdated inMayandNovember 2013.

Search Terms

An experienced research librarianprovided the following predefined listof search terms and medical subjectheadings: children, pediatric, cleftpalate, cranio-facial anomalies, maxillo-facial anomalies, jaw abnormalities,stomatognathic diseases, congenitalanomalies, otitis media with effusion,middle ear effusion, conductive hear-ing loss, grommet tube, ventilationtube, tympanostomy tube, myringotomytube, T-tube, ear tube, pressure equal-ization tube, vent, middle ear ventilation,hearing aids, sensory aids, watchfulwaiting, observation, management, andtreatment.Nolanguagerestrictionswereimposed in these searches.

Study Selection

A dual review process was applied toreview the abstracts of all citationsidentified in the searches. After dupli-cate results were removed, potentiallyrelevant articles were included on thebasis of the full text in the articles.Additional studies were obtained fromthe references of the selected articles.Disagreements were resolved by con-sensus among the senior authors. Onlystudies matching the eligibility criteriawere included in this systematic review.

Data Collection Process

This study used a standardized dataextraction sheet for the articlesdeemed eligible. Data were extractedfrom the included studies by 1 authorand then checked by a second author. Athird author was consulted when anagreement could not be reached. Theauthors of studies were also contactedto obtain additional information whennecessary.

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Risk of Bias and Assessment ofQuality

We assessed the risks of selection andinformation bias at the study level,taking into account the research design(randomized controlled trials or obser-vational studies, prospective or ret-rospective design), sample selection(consecutive or nonconsecutive), eligi-bility criteria (clear or not), diagnosismethods (accurate or inaccurate), andoutcome data (complete or incomplete).Intervention studies were also assessedfor blinding, adequacy of randomization,and withdrawals at the outcome level.We assessed the quality of the methodsused in the selected studies by using an11-item standardized checklist of pre-defined criteria. The checklist was amodified version of an established listof criteriacommonlyused insystematicreviews.23,24 The criteria are presentedin Supplemental Table 7. Each item thatmet the inclusion criteria was assigned1 point. Items that did not meet the cri-teria and those that were not adequatelydescribedwere assigned 0 points. Qualityassessment scores ranged from 0 to 11.Studies scoring .75% of the maximumattainable score (ie, 9–11 points) wereconsidered to be of high quality. Studiesscoring between 51% and 75% of themaximum attainable score (ie, 6–8points) were rated as moderate qual-ity, and studies scoring #50% of themaximumattainable score (ie, 0–5points)were considered low quality.

Strength of the Studies

Thestrengthofstudieson the therapeuticbenefits and harm of treatment optionswere evaluated and classified accordingto criteria published by the Oxford Centrefor Evidence-Based Medicine.25 Level 1was defined as a systematic review ofrandomized trials or single-patient trials.Level 2 was defined as a randomized trialor observational study with dramaticeffects. Level 3 was defined as a non-randomized controlled cohort or follow-

up study. Level 4 was defined as caseseries, case–control studies, or histori-cally controlled studies. Level 5 was de-fined as mechanism-based reasoning.These levels could be downgraded on thebasis of study quality, a lack of precision,indirectness, or inconsistency betweenstudies, or in cases where the absoluteeffect size was small. Conversely, thelevel could be upgraded in cases wherea large effect size was noted. The evi-dence provided in each selected articlewas independently categorized by 2 teammembers according to level.

Summary Measures

The intendedsummarymeasureof effectmayhavediffered fromthatused insomeof the studies; therefore, we prespecifiedthe summary measure of effect for eachoutcome. For hearing outcomes, thenatural effect measure was the differ-ence in hearing ability. For studies withoutcome measurements performed ondifferent scales, measures were sum-marized as the percentage of ears pre-sentinghearing lossor improvement.Forthe frequency of grommet insertion,measures were summarized as thepercentage of ears with $1 grommetinsertion and the frequency of tube in-sertion. For complications or sequelae,the measures were summarized as thefrequency with which complicationsmanifested.

Synthesis of Results

Heterogeneity in the methods used inthe eligible studies rendered them un-suitable for pooled analysis, and addi-tional quantitative analysis was deemedinappropriate or unnecessary. There-fore, the evidence was summarizedqualitatively, andnoattemptwasmadeto perform meta-analysis.

Grading the Strength of Evidence(Quality of Evidence)

To provide a transparent, structuredprocess for presenting evidence, we

graded the quantity, quality, and con-sistency using the evidence gradingscheme developed by the Grading ofRecommendations Assessment, Devel-opment and Evaluation (GRADE) Work-ing Group.26,27 Randomized controlledtrials were initially treated as high-quality evidence, and observationalstudies were considered low-qualityevidence.27 The quality of evidencecould be downrated according to 5factors: risk of bias, inconsistency,indirectness, imprecision, and publica-tion bias. The quality of evidence couldbe uprated according to 3 factors: largeeffect, dose–response gradient, andinclusion of all plausible confounders.Ultimately, evidence was classified into4 categories according to strength: highstrength (additional research is unlikelyto change our confidence in the esti-mate of effect), moderate (additionalresearch is likely to have a notable im-pact on our confidence regarding theestimation of effect), low (additionalresearch is very likely to have a notableimpact on our confidence regardingthe estimation of effect), and very low(any estimate of effect is highly un-certain). A summary table was cre-ated to provide key information aboutthe quality of evidence and the mag-nitude of effect of VTI on all importantoutcomes.

RESULTS

Study Selection

A total of 484 records were identified(Fig 1). Four additional records wereidentified bymanual reference searches.After removing duplicates (115 records),we screened 373 records on the basisof title and abstract. From these, 326records with subjects that were obvi-ously different or irrelevant were elimi-nated. We assessed 47 full-text articlesaccording to the inclusion and exclusioncriteria. Seventeen articles were ex-cluded for the following reasons: caseswith cleft lip only (n = 1), comparison

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between children with and without cleftpalate (n = 4), statistical error (n = 1),more than half of the data missing(n = 1), unavailable (n = 2), informationobtained from questionnaires (n = 5),

and in a language other than English orChinese (n = 3). Four studies evaluatingthe post-VTI outcomes of children withand without cleft palate were excludedfrom this review; however, they are in-

cluded in Supplemental Table 8. Theonly randomized controlled trial in thereview had to be excluded because theauthors did not clearly state whether the2 groups were statistically comparable

FIGURE 1Flow diagram of study retrieval and selection.

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regarding patient characteristics, andin particular because the follow-upperiod was only 6 months for the VTIgroup and 20 months for the controlgroup.28 Furthermore, the methodused for randomization was not men-tioned. To increase the strength of theevidence in this systematic review,low-quality cohort studies (n = 6) andcase series studies (n = 14) were alsoexcluded. These are listed in Supple-mental Table 9. This left a total of 9cohort studies of high or moderatequality for inclusion in the qualitativeintegration of data.

Study Characteristics

Most of the eligible studies (78%) werepublished in the last 2decades, and33%were conducted in the United Kingdom(Table 1). The designs of the studies weincluded were prospective (n = 1) andretrospective (n = 8) cohort studies.Quality assessment revealed that 2 ofthe studies were of high quality and 7studies were of moderate quality. Theevidence presented in these studieswas categorized as follows: level 3(n = 1) and level 4 (n = 8). A total of 702patients with cleft palate were evalu-ated in this review, with a mean ageranging from 3 months to 12 years. Inmost of the cases, follow-up was con-ducted for $3 years.

Comparative Effectiveness of VTIfor Hearing Outcome

Five cohort studies (1 prospective29

and 4 retrospective30–33) in this review

included comparisons of the hearingoutcomes between children receivingVTI and those undergoing non-VTI treat-ments (eg, myringotomy alone fortemporary effusion drainage withoutinsertion of ventilation tube, hearingaids, and watchful waiting) (Table 2).Two studies reported that VTI signifi-cantly improved hearing in childrenwith cleft palate over the short term(#18 months after VTI).31,32 In thestudy by Li et al,31 postoperativehearing was significantly improved inboth the VTI and the non-VTI groups(P, .01). However, the improvementsin the VTI group (26.93 dB above nor-mal adult hearing level) were signifi-cantly greater than those observed inthe non-VTI group (14.13 dB abovenormal adult hearing level; P, .05). Inthe study by Liu et al,32 a significantimprovement in hearing was observedin the VTI group (15.4 dB, P = .01), butnot in the non-VTI group (2 dB, P. .05).Three studies observed no significantdifferences in hearing outcome be-tween VTI and non-VTI groups in a 3- to9-year follow-up period, despite thefact that hearing showed improve-ments postoperatively in children withVTI.29,30,33

Comparative Effectiveness of VTIfor Speech and LanguageOutcomes

Comparisons of speech and languageoutcomes between children with andwithout VTI for OME were performedin 3 cohort studies, including 1 pro-

spective29 and 2 retrospective studies(Table 3).34,35 In the high-quality pro-spective cohort study by Hubbardet al,29 children who had undergoneearly VTI demonstrated significantlybetter consonant articulation andwereless likely to need speech therapy thanthose who had not received this treat-ment. The 2 retrospective studies alsoshowed that VTI is beneficial for speechand language outcomes in childrenwith cleft palate and OME; however,outcome differences between the VTIand non-VTI groups failed to reachsignificance.34,35

Complications and Sequelae of VTIfor OME

Seven of the studies included in thisreview reported post-VTI complicationsand sequelae,29,30,32–34,36,37 5 of whichprovided comparisons of these prob-lems in cases where VTI was or was notimplemented to deal with OME (Ta-ble 4).29,30,33,36,37 Four of the 5 cohortstudies reported a significantly higherrate of complications among childrenwho received VTI, compared with thosewho did not receive this treatment,over the short term (,5 years)30,36,37

and the long term ($9 years).33 OnlyHubbard et al29 reported that the rateof complications differed only slightlybetween the 2 groups.

Eardrum Perforation

Eardrum perforation occurred in 1.3%to 19% of VTI-treated ears during 1 to9 years of follow-up.29,30,33,34,36,37 Two

TABLE 1 Summary of Study Characteristics

Author Design Quality LOE Year Country Intervention and Comparisons Sample Size Age Follow-Up

Hubbard et al29 PC High 3 1985 USA VTI vs observation 6 myringotomy (matched control) n = 48 3–30.8 mo 9 yLiu et al32 RC High 4 2004 China VTI for treated ear vs untreated opposite ears n = 19 5.8 y 6.4 moGani et al30 RC Moderate 4 2012 UK VTI vs HA vs watchful waiting n = 217 N/A 3 yKobayashi et al34 RC Moderate 4 2012 Japan VTI vs non-VTI n = 108 N/A 9.42 yKwan et al36 RC Moderate 4 2011 Hong Kong VTI vs non-VTI n = 84 7.5 y 4.3 yLi et al31 RC Moderate 4 2007 China VTI vs tympanocentesis n = 34 6.6–6.9 mo ,12 moShaw et al35 RC Moderate 4 2003 UK VTI vs non-VTI n = 72 3–4 y 10 yMaheshwar et al37 RC Moderate 4 2002 UK HA vs VTI versus HA plus VTI vs observation n = 70 3.17 y 18 moGordon et al33 RC Moderate 4 1988 New Zealand VTI vs non-VTI n = 50 12 y .9 y

HA, hearing aid; LOE, level of evidence; N/A, not applicable; PC, prospective cohort study; RC, retrospective cohort study; VTI, ventilation tube insertion.

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studies specifically compared the in-cidence of eardrum perforation in VTIand non-VTI groups.29,37 One studyreported a higher rate of eardrumperforation in the VTI group (15.4%)than in the non-VTI group (0%) overthe short term (18 months of follow-up),37 whereas the other study re-ported little difference between theoutcomes in the VTI group (19%)and non-VTI group (21%) over thelong-term (9 years of follow-up).29

Eardrum Retraction

The rate of eardrum retraction wasbetween 11.5% and 36.8% over theshort term (6–18 months of follow-up).32,37 Only 1 study specificallyevaluated the incidence of post-VTIeardrum retraction in children withand without VTI, the results of whichshowed a higher rate of retractedeardrum in the VTI group (11.5%)than in the non-VTI group (2.3%).37

Three other studies also reportedcases of retracted eardrum; however,those studies combined the number ofears with eardrum retraction, ear-drum scarring, and tympanosclerosisinto a single figure.29,33,36 This pre-vented determination of the true in-cidence of eardrum retraction afterVTI.

Tympanosclerosis

Tympanosclerosis was the third mostcommonly reported VTI-related com-plication, with rates ranging from 11%to 37% during 1 to 9 years of follow-up30,32,33,36; however, this problem haslittle influence on hearing.20,38,39 Only1 study specifically compared the in-cidence of tympanosclerosis betweenchildren with VTI (37%) and withoutVTI (2%) during 9 years of follow-up.33

Secondary Acquired Cholesteatoma

Only 2 retrospective cohort studies ofmoderate quality reported that theincidence of post-VTI cholesteatomaTA

BLE2

Effectivenessof

Grom

metsforOM

Ein

ChildrenWith

CleftPalate:Effectson

HearingDevelopm

ent

Author

(Year,Country)

Design,Quality,

LOE

Intervention

Participants

HearingOutcom

es

Hubbardetal29(1985,USA)

PC,high,3

GpI:routineVTIw

ithmoreassiduousantibiotic

treatm

entinchildrenwith

cleftp

alate

n=48

children(GpI24,Gp

II24

matched

for

clefttype,age,gender,socioeconomicstatus,and

birthorder);age

atthetim

eoffirsttreatment:Gp

I3mo,Gp

II30.8mo;ageattesting:Gp

I8.8y,Gp

II9.0y

Hearingbetter

with

earlyVTI(P=.05–0.10).

GpII:Conservativetreatm

ent6

myringotomyin

childrenwith

cleftp

alate

Liuetal32(2004,China)

RC,high,4

GpI:unilateralVTIinears

with

OMEandworse

hearing

n=19

children(38ears;GpI19,Gp

II19);

age5.8y(4–7.5);F/U

6.4mo(2

wk–18

mo)

Significant

hearingimprovem

entinGp

I(42.7–27.3dB,

P=.01)

butn

otinGp

II(29–27

dB,P

..05).

GpII:untreatedoppositeOM

Eears

with

less

hearingimpairment(but

.25

dB)

Ganietal30(2012,UK)

RC,m

oderate,4

GpI:VTI

n=217children(GpI41,Gp

II22,GpIII154);

F/U3y

Both

VTIand

HAimproved

hearingwithoutd

ifference

(P=.47,Gp

IIInotincludedforcomparison).

GpII:HA

GpIII:w

atchfulw

aiting

Lietal31(2007,China)

RC,m

oderate,4

GpI:bilVTIs

n=34

children(68ears;GpI38,Gp

II30);ageat

intervention:Gp.I6.9mo(2–12),Gp

II6.6mo

(2–12);F/U1wkto

12mo

Thehearingwas

improved

inboth

GpIand

IIpostoperatively(P

,.01).

GpII:biltym

panocentesis

GpIhad

moreimprovem

entinhearingthan

GpII(26.93

dBabovenorm

aladulthearing

levelvs14.13dB

above

norm

aladulthearinglevel,P,

.05).

Gordon

etal33(1988,New

Zealand)

RC,m

oderate,4

GpI:VTIatthetim

eofpalatoplastyor

later

n=50

children(100

ears;GpI50,Gp

II50);mean

ageatlatestF/U12

y(9–17);F/U$9yafter

palatoplasty

Hearingresults

#20

dB:GpI71%

(34/48)vs

GpII88%

(44/50,P

..05).

GpII:non-VTI

Palatoplastyat5and9moofage

bil,bilateral;F/U,follow-up;Gp,group;HA,hearingaid;LOE,levelofevidence;PC,prospectivecohortstudy;RC,retrospectivecohortstudy;VTI,ventilationtube

insertion.

988 KUO et al by guest on June 29, 2018www.aappublications.org/newsDownloaded from

was low among children with cleftpalate over the short term (3.8%, 18months)37 and the long term (0%, .9years).33 Both studies also reportedthat the incidence of cholesteatomawas comparable in VTI and non-VTIgroups.

Otorrhea

Only 1 retrospective cohort study ofmoderate quality reported cases ofpost-VTI otorrhea.37 That study identi-fied post-VTI otorrhea in 11.5% of chil-dren with cleft palate, whereas nocases of otorrhea were identifiedamong children with hearing aids orthose undergoing watchful waiting.The follow-up period of that study was18 months.

Frequency of Grommet Insertion

The frequency of grommet insertionwas estimated from 5 studies (Ta-ble 5).33–37 During a follow-up period of4 to 9 years, 38% to 53% of childrenwith cleft palate underwent$1 VTIs forOME.34,36,37 Maheshwar et al37 reportedthat the average number of VTIs neededfor OME in children with cleft palatewas 1.7 during a follow-up period of 18months. In addition, the number of VTIswas found to be significantly associ-ated with cleft type, with severe orcomplete clefts more likely to undergogrommet insertion.33,35

Strength of Evidence

After the quantity, quality, and consis-tencyof evidenceweresummarized, thestrength of evidence regarding the ef-fectiveness of grommet insertion forOME in children with cleft palate wasconsidered very low for all outcomes:hearing, speech and language, compli-cations, and frequency of VTI (Table 6).

DISCUSSION

Compared with conservative manage-ment, VTI can be beneficial for the re-

covery of hearing in children with cleftpalate and OME over the short termandthe long term (Table 2).29–33 Threestudies address the effectiveness ofgrommets on speech and languagedevelopment in children with cleftpalate.29,34,35 According to these re-sults, children with cleft palate couldbenefit from VTI (Table 3). In a high-quality prospective cohort study byHubbard et al,29 equal numbers ofchildren were matched for cleft type,age, gender, socioeconomic status, andbirth order. After a follow-up of 9 years,children with early VTI were shown tohave significantly better consonantarticulation and were less likely toneed speech therapy than those whohad not undergone the procedure.In the VTI group, myringotomy wasfollowed by tube insertion for thecontinuous drainage of middle eareffusion, and in the control group asingle myringotomy without tube in-sertion was performed for the tempo-rary drainage of effusion when deemednecessary. Thus, it could be reasonableassumed that watchful waiting (ie,without temporary drainage of middleear effusion by a single myringotomy)may have a more deleterious effecton the development of consonant ar-ticulation, with subsequent effectson speech and language outcomes.However, clinical practitioners shouldbe aware that speech and languageskills depend not only on the approachto the management of OME but alsoon the timing in the application ofpalatoplasty.

Childrenwithcleftpalategenerallyhavea higher risk of post-VTI complicationsthan those who did not receive thistreatment over the short term (,5years)30,36,37 and the long term ($9years) (Table 4).33 In the study byHubbard et al,29 only a slight differencewas observed in the rate of compli-cations between the VTI and non-VTIgroups; however, some of those childrenTA

BLE3

Effectivenessof

Grom

metsforOM

Ein

ChildrenWith

CleftPalate:Effectson

Speech

andLanguage

Developm

ent

Author

(Year,Country)

Design,Quality,

LOE

Intervention

Participants

Speech

andLanguage

Hubbardetal29

(1985,USA)

PC,high,3

GpI:routineVTIw

ithmoreassiduousantibiotic

treatm

entinchildrenwith

cleftpalate

n=48

children(GpI24,Gp

II24

matched

for

clefttype,age,gender,socioeconom

icstatus

andbirth

order);age

atthetim

eoffirsttreatment:Gp.I3mo,Gp

II30.8mo);age

attesting:Gp

I8.8y,Gp

II9.0y

Consonantarticulationbetter

with

earlyVTI(P=.03).

GpII:Conservativetreatm

ent6

myringotomy

inchildrenwith

cleftp

alate

GpIreceivedless

speech

therapythan

GpII.

Kobayashietal34(2012,

Japan)

RC,m

oderate,4

VTIinchildrenwith

cleftpalateandOM

Eat

age

1–5y

n=108children(216

ears;GpI82,Gp

II134);

F/U9.42

y(6–13)

Thedifferenceinthelanguage

developm

entb

etweenGp

IandIIwas

notsignificant.

GpI:VTIgroup

GpII:non-VTIgroup

Shaw

etal35

(2003,UK)

RC,m

oderate,4

GpI:VTIfor

symptom

aticOM

En=72

children(GpI20,Gp

II52);speech

assessmentswere

carriedoutattheageof3–4y;F/U10

yEars

with

VTIhad

better

speech

outcom

esthan

those

without(butP

..05).

GpII:non-VTIfor

subclinicalOM

E

F/U,follow-up;Gp,group;LOE,levelofevidence;PC,prospectivecohortstudy;RC,retrospectivecohortstudy;VTI,ventilationtube

insertion.

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TABLE4

Effectivenessof

Grom

metsforOM

Ein

ChildrenWith

CleftPalate:Com

plications

andSequelae

Author

(Year,

Country)

Design,Quality,

LOE

Intervention

Participants

Complications

andSequelae

Hubbardetal29

(1985,USA)

PC,high,3

GpI:routineVTIw

ithmoreassiduousantibiotic

treatm

entinchildrenwith

cleftpalate

n=48

children(GpI24,Gp

II24

matched

forclefttype,

age,gender,socioeconom

icstatus

andbirthorder);age

atthetim

eoffirsttreatment:Gp

I3mo,Gp

II30.8mo;age

attesting:Gp

I8.8y,Gp

II9.0y

Littledifferenceinthecomplications

betweengroups:

GpII:conservativetreatm

ent6

myringotomyin

childrenwith

cleftp

alate

Norm

alTM

:GpI21%

vsGp.II21%

Activeotitismedia:GpI4%vs

GpII4%

TMperforationor

VTinplace:Gp

I19%

vsGp

II21%

TMretraction,atelectasis,or

TMscarring:GpI56%

vsGp

II54%

Liuetal32

(2004,China)

RC,high,4

GpI:unilateralVTIinears

with

OMEandworse

hearing

n=19

children(38ears;GpI19,Gp

II19);age5.8y

(4–7.5);F/U

6.4mo(2

wk–18

mo)

ComplicationinGp

I

GpII:untreatedoppositeOM

Eears

with

less

hearingimpairment(but.

25dB)

Tympanosclerosis:21.2%

TMretraction:36.8%

Norm

alTM

:26.3%

Pars

tensascaring:15.7%

Ganietal30

(2012,UK)

RC,m

oderate,4

GpI:VTI

n=217children(GpI41,Gp

II22,GpIII154);

F/U3y

VTI-related

complications:25.5%

GpII:HA

Tympanosclerosis:11%

GpIII:w

atchfulw

aiting

TMperforation:11%

HA-related

complications:9.1%(P

,.05)

Kobayashietal34

(2012,Japan)

RC,m

oderate,4

VTIinchildrenwith

cleftp

alateandOM

Eatage1–5y

n=108children(216

ears;GpI82,Gp

II134);

F/U9.42

y(6–13)

Rateoffavorableoutcom

e(noOM

Eeven

atage$5or

OMEhealed

inresponse

toconservativetreatm

ent)

afterage6:VTI68.3%

(56/82)vs

non-VTI95%

(95/100)

GpI:VTIgroup

TMperforationinGp

I:6.6%

GpII:non-VTIgroup

Kwan

etal36(2011,

Hong

Kong)

RC,m

oderate,4

VTIincleftpatientsw

ithOM

E(80.5%ofVTIsconcurrent

with

palatoplasty)

n=84

children(125

patient-earswith

OME;80

with

VTI,45

without);age

7.5y(2.7–12.4);F/U4.3y

Ratesofcomplications

inears

withoutVTI(0%)andwith

VTI(15.7%,P

=.013)

VTIgroup

TMretractionor

tympanosclerosis:12.6%

Non-VTIgroup

TMperforation:1.3%

Maheshw

aretal37

(2002,UK)

RC,m

oderate,4

GpI:HA

n=70

children(GpI17,Gp

II12,GpIII14,GpIV27);ageat

firstu

seofHA:3

yand2mo(12mo–8y);F/U

18mo

Complicationrate:childrenwith

VTI(Gp

II+III)38.4%vs

withoutVTI(GpI+

IV)4.5%

(P,

.005)

GpII:VTI

TMretraction:VTI(+)

11.5%vs

VTI(2)2.3%

GpIII:HA+VTI

TMperforation:VTI(+)

15.4%vs

VTI(2)0%

GpIV:observation

Persistent

otorrhea:VTI(+)11.5%vs

VTI(2)0%

Bilcholesteatoma:VTI(+)

3.8%

vsVTI(2)0%

Gordon

etal33(1988,

NewZealand)

RC,m

oderate,4

GpI:VTIatthe

timeofpalatoplastyor

later

n=50

children(100

ears;GpI50,Gp

II50);meanageat

latestF/U12

y(9–17);F/U$9yafterpalatoplasty

Higher

rateofabnorm

alTM

inears

with

VTI(Gp

I72%

,Gp

II14%,P

,.001;excluding

7ears

with

VTinplace)

GpII:non-VTI

Tympanosclerosis:Gp

I37%

vsGp

II2%

Palatoplastyat5and9moofage

TMscarring

orretraction:Gp

I26%

vsGp

II8%

OME:Gp

I5%vs

GpII0%

TMperforation:Gp

I5%

Cholesteatom

a:Gp

IorII0%

bil,bilateral;F/U,follow-up;Gp,group;HA,hearingaid;LOE,levelofevidence;PC,prospectivecohortstudy;RC,retrospectivecohortstudy;TM

,tym

panicmem

brane;VTI,ventilationtube

insertion.

990 KUO et al by guest on June 29, 2018www.aappublications.org/newsDownloaded from

received conservative treatment involv-ing myringotomy without tube insertionfor the temporary drainage of effusion.We believe that this may have increasedthe rate of complications in areas suchas eardrum perforation and scarringand could partly explain the similarcomplication rates observed in the VTIand non-VTI groups.

Among the various types of complica-tion, eardrum perforations (incidence1.3%–19%) are the most commonlyreported sequelae after VTI,29,30,33,34,36,37

followed by eardrum retraction (in-cidence 11.5%–36.8%)29,32,33,36,37 andtympanosclerosis (incidence 11%–37%).30,32,33,36 In contrast, cholesteatoma(incidence 0%–3.8%)33,37 and otorrhea(incidence 11.5%)37 are rarely reportedas complications of VTI. Unfortunately,the available evidence is insufficient toenable a specific comparison of eachcomplication between VTI and non-VTIgroups. It is therefore difficult to iden-tify the magnitude of effect of eachcomplication on children with andwithout VTI.

Otorrhea is known as a complication ofinserting tympanostomy tubes in chil-dren who are otherwise healthy40;however, post-VTI otorrhea in childrenwith cleft palate has not been com-prehensively examined in moderate- orhigh-quality cohort studies. A numberof low-quality cohort and case seriesstudies (not included in our integratedresults) reported inconsistent find-ings about the probability of post-VTIotorrhea occurring in children withcleft palate, ranging from low estimates(4%–11.5%)41,42 to high (55%–68%).43–45

For other complications and sequelae,such as the occlusion of grommets andthe presence of granulation tissue, theevidence was too limited and blurredto determine the direction of the effectbetween VTI and adverse events in thechildren with cleft palate and OME.

A large percentage (38%–53%) of thechildren with cleft palate underwentTA

BLE5

Effectivenessof

Grom

metsforOM

Ein

ChildrenWith

CleftPalate:Frequency

ofTreatm

ent

Author

(Year,Country)

Design,Quality,LOE

Intervention

Participants

FrequencyofTreatm

ent

Kobayashietal34

(2012,Japan)

RC,m

oderate,4

VTIinchildrenwith

cleftp

alateandOM

Eat

age1–5y

n=108children(216

ears;GpI82,Gp

II134);

F/U9.42

y(6–13)

38%ofallearshad$1VTIs(allchildrenwith

cleft

palate).

GpI:VTIgroup

GpII:non-VTIgroup

Kwan

etal36(2011,

Hong

Kong)

RC,m

oderate,4

VTIinpatientswith

cleftp

alatewith

OME(80.5%

ofVTIsconcurrent

with

palatoplasty)

n=84

children(125

patient-earswith

OME;

80with

VTI,45

without);age

7.5y(2.7–12.4);F/U4.3y

53.2%ofallpatientshadVTI.

VTIgroup

Non-VTIgroup

Shaw

etal35

(2003,UK)

RC,m

oderate,4

GpI:VTIfor

symptom

aticOM

En=72

children(GpI20,Gp

II52);speech

assessmentswerecarriedoutattheageof3–4y;F/U10

ySevere

cleftsaremorelikelytohave

grom

metsinserted

(P=.30).

GpII:non-VTIfor

subclinicalOM

EMaheshw

aretal37

(2002,UK)

RC,m

oderate,4

GpI:HA

n=70

children(GpI17,Gp

II12,GpIII14,GpIV27);

ageatfirstusage

ofHA:3

yand2mo(12mo–8y);F/U

18mo

AveragenumberofVTIs:1.7.

GpII:VTI

GpIII:HA+VTI

GpIV:observation

Gordon

etal33(1988,

NewZealand)

RC,m

oderate,4

GpI:VTIatthe

timeofpalatoplastyor

later

n=50

children(100

ears,GpI50,Gp

II50);mean

ageatlatestF/U12

y(9–17);F/U$9yafterpalatoplasty

Morepatientswith

completecleftshadrepeated

VTIs

than

thosewith

incompleteclefts.

GpII:non-VTI

Palatoplastyat

5and9moofage

bil,bilateral;F/U,follow-up;Gp,group;HA,hearingaid;LOE,levelofevidence;RC,retrospectivecohortstudy;VTI,ventilationtube

insertion.

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$1 VTIs for OME.34,36,37 Cleft defectsplay an important role in OME forma-tion; therefore, it is reasonable to as-sume that grommets are more likely tobe needed for children with more overtpalatal malformations. This assump-tion is supported by the cohort studiesincluded in this review,33,35 in which therelationship between the severity ofthe cleft and frequency of VTI wasestablished, with severe or completeclefts presenting a greater likelihoodof necessitating grommet insertion.

One question that must be addressedwith regard to VTI for OME in childrenwithcleftpalate is the timingofgrommetinsertion. The studies in this review in-dicate that grommets are generallyinserted on 2 occasions: therapeuticinsertion for children with symptoms orsigns of OMEand prophylactic VTIs at thetime of palatoplasty. Despite a belief thatearly VTI at the time of palatoplasty isbeneficial,46 the existing evidence re-mains insufficient to support any as-sertions about the optimal timing ofgrommet insertion.

Strength of Evidence

All studies included in this review wereobservational cohort studies, whichwere initially graded as low-qualityevidence according to the GRADE ap-proach.27 For each outcome, the stud-ies were unable to adequately controlfor known confounding factors.47 Inaddition, differences in the measure-

ment of outcomes may also have in-creased the risk of bias in the outcomeresults.47 For example, some of thestudies obtained absolute thresholdsusing standard pure tone audiometryfor the measurement of hearing out-comes,31,32 whereas 1 study used thepercentage of ears with hearing thresh-olds #20 dB (normal limit).33 Further-more, there was a high probability ofpublication bias with each outcomebecause of the small number of partic-ipants in the observational studies.48

Taking these factors into consider-ation, we must lower the strengthclassification of evidence for eachoutcome. Based on the GRADE approach,we conclude that the strength of evi-dence regarding the effectiveness of VTIfor OME in children with cleft palatewas very low for each outcome, in-cluding hearing, speech and language,complications, and frequency of VTI(Table 6).

Limitations

This review had the following limi-tations. First, there is a notable lack ofhigh-quality randomized controlledtrials evaluating the effectiveness ofVTI forOME in childrenwith cleft palate.As a result, nonrandomized cohortstudies of high or moderate qualityprovided the only available evidencefor this review. Second, we did notexamine non-English or non-Chinesestudies in our review. We identified

only 3 non-English or non-Chineselanguage articles (1 in Spanish and 2in German), which were excluded fromthe review because we were unableto obtain complete articles. However,it is probable that no qualitative orquantitative differences exist betweenstudies written in English or any otherlanguage with regard to how theauthors deal with health equity orreport their results.49 Egger et al50

claimed that a search for English lit-erature in PubMed is sufficient formost systematic reviews. Furthermore,Cochrane reviews do not impose lan-guage restrictions; however, all theirstudies are published in English.14 Giventhe large literature base we used, webelieve that we captured most of therelevant studies, and it is unlikely thatthe conclusions of this review were af-fected by the exclusion of non-Englishstudies. The nature of retrospective,uncontrolled studies makes them par-ticularly susceptible to selection biaswith regard to which patients receivedtubes and which patients did not. Thismakes it difficult to draw conclusionsabout the actual contribution of thetubes to the assessed outcomes. Spe-cifically, during the assessment of chil-dren as candidates for tube insertion,those with more pronounced delaysin speech and language developmentwould be more likely to receive tubesand therefore end up in the VTI group.Similarly, children with more pronounced

TABLE 6 Summary of Strength of Evidence on the Effectiveness of Grommets for OME in Children With Cleft Palate

Outcomes Study Design No. of Studies No. of Participants Findings and Direction of Effect Strength of Evidence

Hearing Cohort studies 5 368 Compared with a conservative approach, VTI may improvehearing outcomes in the children with cleft palate and OME.

Åsss

Very lowSpeech and language Cohort studies 3 228 VTI may bring benefits to children with cleft palate and OME in

speech and language.Åsss

Very lowComplications Cohort studies 5 469 Children with VTI may have a higher risk of complications than

those who undergo conservative treatments. The mostcommon post-VTI complications would be eardrum retractionand tympanosclerosis, with incidence of ~11%–37%.

Åsss

Very low

Frequency of VTI Cohort studies 5 384 A large percentage (38%–53%) of children with cleft palate mayneed$1 VTIs for OME, with patients with severe or completeclefts more likely to have grommet insertion.

Åsss

Very low

OME, otitis media with effusion; VTI, ventilation tube insertion.

992 KUO et al by guest on June 29, 2018www.aappublications.org/newsDownloaded from

baseline retraction, effusion, or hearingloss would also be more likely to endup in the VTI group. A comparison ofbaseline factors in the study can beused to control for this bias but only toa limited degree. The direction of thisbias would be against the positiveeffects of VTI.

Future Research Needs

All studies included in this review werecohort studies with a heterogeneousstudy design, which was a barrier toevidence synthesis. Future investigationsmayrequire thedevelopmentof rigorousmethodstoexaminefunctionaloutcomesin children with cleft palate after VTI.Great attentionmust be paid to the studymethods to improve the literature baseand facilitate cross-study integration.

CONCLUSIONS

To the best of our knowledge, this isthe first systematic review to addressthe effects of VTI on children with cleftpalate and OME according to patient-centered outcomes. We followed the

protocol outlined in Preferred ReportingItems for Systematic reviews and Meta-Analyses to fully and transparently as-sess the existing literature, to provideevidence-based information about themanagementofOME inchildrenwithcleftpalate. First, 38% to 53% of the childrenwith cleft palate underwent VTI for OME,and more severe cases appeared morelikely to undergo grommet insertion.Second, compared with a conservativeapproach, VTI may improve hearingoutcomes in the children with cleft pal-ate. The improvementshavebeen shownto remain for 1–9 years after surgery.Third, VTI may benefit children with cleftpalate and OME in the development ofspeech and language. In addition, chil-dren who have undergone VTI facea higher risk of complications thanthosewho have not received this form oftreatment. The most common post-VTIcomplications are eardrum retractionand tympanosclerosis, with incidencerates of 11% to 37%. Of particular im-portance is the need to perform grom-met insertion within a highly specified

time frame. At present, the existing evi-dence is insufficient to support anyassertions about the use of grommetseither therapeutically or prophylactically,at the time of palatoplasty or later. Al-though the results of this study are ev-idence based, the studies included inthe analysis are underpowered cohortstudies, and the evidence for each out-come is of very low strength. Therefore,well-designed randomized controlledtrials will be needed to verify the con-clusions of this study. Additional pro-spective studies comparable betweeninstitutes will also be needed to developa comprehensive evidence base withwhich to validate the conclusions in thissystematic review.

ACKNOWLEDGMENTSWe thank the Biostatistics Task ForceandDigitalMedical Library, Taipei Veter-ans General Hospital, Taipei, Taiwan, Re-public of China, for their support inassembling this review, including con-sultations with experienced biostatisti-cians and librarians.

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(Continued from first page)

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

Copyright © 2014 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.

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DOI: 10.1542/peds.2014-0323 originally published online October 6, 2014; 2014;134;983Pediatrics 

Hsu, Chii-Yuan Huang and An-Suey ShiaoChin-Lung Kuo, Yuan-Heng Tsao, Hao-Min Cheng, Chiang-Feng Lien, Chyong-Hsin

Systematic ReviewGrommets for Otitis Media With Effusion in Children With Cleft Palate: A

ServicesUpdated Information &

http://pediatrics.aappublications.org/content/134/5/983including high resolution figures, can be found at:

Referenceshttp://pediatrics.aappublications.org/content/134/5/983#BIBLThis article cites 47 articles, 4 of which you can access for free at:

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DOI: 10.1542/peds.2014-0323 originally published online October 6, 2014; 2014;134;983Pediatrics 

Hsu, Chii-Yuan Huang and An-Suey ShiaoChin-Lung Kuo, Yuan-Heng Tsao, Hao-Min Cheng, Chiang-Feng Lien, Chyong-Hsin

Systematic ReviewGrommets for Otitis Media With Effusion in Children With Cleft Palate: A

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