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FACULTEIT GENEESKUNDE EN GEZONDHEIDSWETENSCHAPPEN
Academiejaar 2012 - 2013
The effects of lip adhesion on maxillary growth in
bilateral cleft lip patients: a systematic review
Lien VAN QUICKELBERGHE
Promotor: Prof. dr. Guy De Pauw
Masterproef voorgedragen in de Master na Master Opleiding Orthodontie
FACULTEIT GENEESKUNDE EN GEZONDHEIDSWETENSCHAPPEN
Academiejaar 2012 - 2013
The effects of lip adhesion on maxillary growth in
bilateral cleft lip patients: a systematic review
Lien VAN QUICKELBERGHE
Promotor: Prof. dr. Guy De Pauw
Masterproef voorgedragen in de Master na Master Opleiding Orthodontie
De auteur(s) en de promotor geven de toelating deze Masterproef voor consultatie
beschikbaar te stellen en delen ervan te kopiëren voor persoonlijk gebruik. Elk ander gebruik
valt onder de beperkingen van het auteursrecht, in het bijzonder met betrekking tot de
verplichting uitdrukkelijk de bron te vermelden bij het aanhalen van resultaten uit deze
Masterproef.
Datum, 30/04/2013
Van Quickelberghe Lien Prof. dr. Guy De Pauw
Voorwoord
Mijn eerste ervaringen met het schrijven van een thesis zijn niet onopgemerkt voorbij gegaan.
Daarom is het op zijn plaats om enkele mensen in de bloemetjes te zetten.
Eerst en vooral zou ik graag Prof. dr. De Pauw bedanken voor de hulp bij het realiseren van
deze thesis en voor de onderzoeksbesprekingen.
Een speciaal woordje van dank gaat uit naar mijn 4 mede-collegaatjes. Gedurende de laatste
vier jaar overwonnen we samen alle hindernissen en we konden steeds bij elkaar terecht met
onze vragen. En de junioren zorgden voor een leuke ontspanning tijdens onze dagelijkse K12
bezoekjes. Daarnaast ben ik Michaël heel dankbaar om mij bij te staan met de metingen en het
vinden van het juiste programma. Ook Laurent mag zeker niet ontbreken. Hij was mijn
rechterhand tijdens het maken van de review.
Verder wil ik ook mijn ouders, broer, zus en schoonouders bedanken voor de talloze uurtjes
dat ze Wout opgevangen hebben. Zij maakten het mogelijk dat ik ongestoord kon verder
werken. Mijn ouders gaven mij de mogelijk om de tandheelkundige opleiding te volgen en
daarvoor ben ik hen eeuwig dankbaar.
Een laatste dankwoord gaat uit naar mijn vriend Rainer en mijn zoontje Wout. Door jullie
positieve ingesteldheid en vrolijkheid kon ik altijd bij jullie terecht voor de gepaste
ontspanning. Ik kon ook altijd op jullie steun rekenen. Ik kan mij geen mooier gezinnetje
voorstellen!
Tabel of contents
Samenvatting .............................................................................................................................. 1
Abstract ...................................................................................................................................... 2
1 Introduction ........................................................................................................................ 3
1.1 Classification ............................................................................................................... 3
1.2 Developmental pathogenesis ....................................................................................... 4
1.3 Aetiology ..................................................................................................................... 5
1.4 Phenotypic aspects of bilateral cleft lip ....................................................................... 6
1.4.1 Dental anomalies .................................................................................................. 6
1.4.2 Speech pathology ................................................................................................. 6
1.4.3 Craniofacial morphology ...................................................................................... 6
1.4.4 Craniofacial morphology of adult with un-operated BCLP ................................ 7
1.5 Management of premaxillary protrusion ..................................................................... 7
1.5.1 Latham appliance ................................................................................................. 8
1.5.2 Passive nasoalveolar moulding appliance (PNAM) ............................................. 9
1.5.3 Lip taping ........................................................................................................... 11
1.5.4 Lip adhesion ....................................................................................................... 12
1.6 Treatment protocols ................................................................................................... 15
2 Review of the literature .................................................................................................... 16
2.1 Material and methods ................................................................................................ 16
2.2 Results ....................................................................................................................... 19
2.2.1 Search results ...................................................................................................... 19
2.2.2 Flow diagram of study inclusion ........................................................................ 21
2.2.3 Inter-reliability (Kappa-coefficient) ................................................................... 22
2.2.4 Characteristics of excluded studies .................................................................... 23
2.2.5 Characteristics of included studies ..................................................................... 24
2.2.6 Description of included articles .......................................................................... 28
3 Discussion ........................................................................................................................ 33
4 Conclusion of the review .................................................................................................. 36
5 Pilot study ......................................................................................................................... 37
5.1 Protocol for future research ....................................................................................... 37
5.1.1 Aim ..................................................................................................................... 37
5.1.2 Null hypothesis ................................................................................................... 37
5.1.3 Method ............................................................................................................... 37
5.1.4 Statistical analysis .............................................................................................. 41
5.2 Results ....................................................................................................................... 42
5.2.1 Error of the method ............................................................................................ 42
5.2.2 Vertical changes of the premaxilla (z-value) ..................................................... 43
5.2.3 Sagittal changes of the premaxilla (y-value) ...................................................... 45
5.2.4 Transversal changes of the premaxilla (x-value) ............................................... 45
5.3 Discussion .................................................................................................................. 46
6 References ........................................................................................................................ 49
7 Attachments ...................................................................................................................... 54
7.1 Attachment 1: Quality assessment included articles ................................................. 54
7.1.1 Hak, Sasaguri (54) .............................................................................................. 54
7.1.2 Gatti, Lazzeri (55) .............................................................................................. 56
7.1.3 Millard, Latham (56) .......................................................................................... 58
7.1.4 Rintala and Haataja (33) ..................................................................................... 60
7.1.5 Van der Beek, Hoeksma (57) ............................................................................. 62
7.2 Attachment 2: License agreement (Elsevier) ............................................................. 64
1
Samenvatting
Doel: Deze systematische review heeft als doel het bepalen van het effect van lipadhesie op
de maxillaire groei bij patiënten met bilateraal gespleten lip en verhemelte (BCLP).
Materiaal en methode: Een zoektocht doorheen de literatuur werd uitgevoerd voor de
lipadhesie procedure bij patiënten met bilateraal gespleten lip en verhemelte. De zoektermen
“bilateral cleft lip and palate” en/of “lip adhesion” werden gebruikt. Verscheidene
elektronische databanken (Medline, Cochrane en Web of Science) werden doorzocht door 2
onafhankelijke onderzoekers voor de jaren 1985 tot heden. Alle titels en samenvattingen
werden gescreend door dezelfde onderzoekers en irrelevante artikels, case reports en
duplicaten werden verwijderd. Vervolgens werd een tweede selectie uitgevoerd a.d.h.v.
volgende inclusie criteria: studies uitgevoerd op mensen met BCLP en klinisch onderzoek met
minimum 5 patiënten. De referentielijst van alle geselecteerde artikels werd doorzocht en er
werd een kwaliteitscontrole uitgevoerd op de artikels weerhouden na de tweede selectie.
Resultaten: Oorspronkelijk werden 110 artikels gevonden in Medline, 8 in cochrane en 90
artikels in Web of Science. Na rekening te houden met de inclusie criteria en het uitvoeren
van een kwaliteitscontrole bleven 5 relevante artikels over. Door de grote diversiteit aan
behandelplanning en chirurgische aanpak konden de resultaten enkel besproken en niet
gepoold worden. In patiënten met BCLP, resulteerde lipadhesie in een significante reductie
van de cleft aan beide zijden en van de protrusie van de premaxilla. Eén artikel besloot dat
lipadhesie een tijdelijk negatief effect had op de groei van de tandbogen in drie dimensies.
Conclusie: Lipadhesie maakt van een complete, brede cleft een onvolledige cleft met een
betere alignatie van laterale maxillaire segmenten en de premaxilla en vereenvoudigt zowel de
definitieve lipsluiting als de cheilognathoplastie.
Dit abstract werd aanvaard door de European Orthodontic Society en zal voorgesteld worden
als poster in juni 2013 op het jaarlijks Europees congres te Reykjavik (IJsland).
2
Abstract
Aim: The purpose of the systematic review is to investigate the effects of lip adhesion on the
maxillary growth of bilateral cleft lip and palate patients.
Materials and methods: A literature search strategy was performed on the procedure of lip
adhesion in bilateral cleft lip and palate patients. The following search terms were used:
“bilateral cleft lip and palate” and/or “lip adhesion”. Several electronic databases (Medline,
Cochrane and Web of Science) were searched by two independent investigators for the years
1985 until 2013. The titles and abstracts of all the retrieved papers were screened
independently by the 2 investigators. The articles, irrelevant for the research, case reports and
duplicates were eliminated. Subsequently, a second selection was made following specific
inclusion criteria: human studies, bilateral cleft lip and palate and clinical trials with at least
5 patients. The reference lists of included studies were screened for further relevant articles. A
quality assessment tool was applied on all the articles meeting the inclusion criteria.
Results: Initially, 110 articles were identified in Medline, 8 in Cochrane and 90 in Web of
Science. After the selection according the inclusion criteria and the quality assessment, a total
of 5 eligible articles remained. Due to severe heterogeneity of the treatment protocols and
surgical approach, the results were summarized without pooling. In patients with bilateral
cleft lip and palate, lip adhesion resulted in a significant reduction of the cleft width on both
sides and of the protrusion of the premaxilla. Only one article mentioned that lip adhesion had
a temporary negative effect on the growth of dental arch dimensions.
Conclusion: Lip adhesion converts a complete wide cleft to an incomplete cleft with a better
alignment of the three maxillary segments and makes both definitive lip closure and
cheilognathoplasty easier.
3
1 Introduction
1.1 Classification
Orofacial clefts are the most common craniofacial birth defects in humans, with an average
worldwide prevalence at birth of 1,7/1000. (1) The birth prevalence varies depending on
several factors, including infant sex, race/ethnicity, and maternal age. (2) In combined data
from European registries for 1995 - 99 3,5% of babies with cleft lip with or without cleft
palate were stillborn and 9,4% were from terminated pregnancies. (3-5) Cleft lip with or
without cleft palate is most frequent in males, and isolated cleft palate is most typical in
females, across various ethnic groups. (6) Rates of cleft lip with or without cleft palate were
high in parts of Latin America and Asia and low in Israel, South Africa, and southern Europe.
Rates of isolated cleft palate were high in Canada and parts of northern Europe. (7)
Orofacial clefts can be divided into 2 categories:
1. Cleft lip with or without cleft palate (CLP or CL)
2. Isolated cleft palate (CP)
These groups can be subdivided into unilateral or bilateral clefts. For children with CLP,
about twice as many infants have unilateral versus bilateral involvement and for CL, there are
over 10 times as many with unilateral versus bilateral involvement. (2) A further subdivision
of orofacial clefts into ‘syndromic’ versus ‘isolated’ forms depends on whether additional
structural and/or developmental anomalies occur with the cleft. (8) The proportion of
orofacial clefts associated with specific syndromes is between 5 and 7%. (9)
A bilateral cleft lip presents in a wide spectrum. The most common type is symmetrically
complete with a protrusive central premaxillary-vomerine element flanked by disconnected
maxillary-palatine segments. Symmetrical incomplete forms are less common and are usually
accompanied by small alveolar clefts and an intact secondary palate. Asymmetrical bilateral
cleft lip is either complete or incomplete on the larger side with an incomplete or a lesser form
on the other side. [(10)- Figure 1]
4
Figure 1: Subdivision bilateral cleft lip. The most common type is symmetrically complete cleft lip.
Symmetrical incomplete forms are less common and are usually accompanied by small alveolar clefts and an
intact secondary palate. Asymmetrical bilateral cleft lip is either complete or incomplete on the larger side with
an incomplete or a lesser form on the other side. (10)
1.2 Developmental pathogenesis
Development of the lip and palate entails a complex series of events that require close
coordination of programs for cell migration, growth, differentiation and apoptosis. (7)
In the first four weeks of embryogenesis there is a rapid period of facial development. Upper
lip formation (merging of different prominences) is complete by about the sixth or seventh
week. (11) This occurs by the merging of mesoderm from within one prominence with the
neighbouring prominence and an epithelial bridging occurs actively at the borders. This
‘dynamic fusion’ theory suggests that mesenchymal tissue may be the driving force for
epithelial bridging. (12)
Bilateral cleft lip
Symmetrical complete Symmetrical incomplete Asymmetrical
Larger side Smaller side
Incomplete
Incomplete
Minor-form
Microform
Mini-
microform
Complete
5
Figure 2 Diagrammatic representation of the steps of fusion in a theoretical pair of facial prominences.
Failure of any of these stages of the fusion process can result in an orofacial cleft. (12)
In cleft patients, there’s a lack of mesenchyme tissue derivatives within the cleft. Thus, the
dynamic fusion theory suggests that failure of apposition of mesoderm between prominences
leads to failure of epithelial bridging, resulting in a cleft. Failure on one side results in a
unilateral cleft, failure on both sides in a bilateral cleft. Different degrees of extent of failure
result in variations in cleft deformity. (13)
1.3 Aetiology
Clefts have a complex aetiology and likely result from an interaction between environmental
and genetic factors. (14)
Smoking during pregnancy has been identified as the most consistent environmental risk
factor. (15) Other environmental factors are vitamin B6, folic acid, Zinc, riboflavin or
vitamin A deficiency caused by poor maternal nutrition, maternal alcohol abuse, maternal
occupational exposure to organic solvents, parental exposure to agricultural chemicals,
maternal corticosteroid use and obesity. (7) In nonsyndromic clefts, environmental factors
play a significant role. (13)
Due to the complex nature of embryogenesis, there are many potential areas for disruption in
development which can result in clefting. Micro deletions in chromosome 22q11.2 have been
found to be associated with three known syndromes, DiGeorge, velocardiofacial and
conotruncal anomaly face, featuring cleft palates. (16)
6
1.4 Phenotypic aspects of bilateral cleft lip
1.4.1 Dental anomalies
Cleft individuals present significantly more dental anomalies than individuals without cleft
lip/palate. Tooth agenesis, microdontia, malpositioned teeth, transposition, supernumerary
teeth and multiple anomalies are consistently more frequent in cleft patients. Tooth impaction
also tends to be more common. Regarding tooth agenesis, excluding third molars, lateral
incisors and premolars are most commonly absent with no significant differences regarding
each individual's cleft status. Individuals without clefts present more agenesis of the lateral
incisors. Tooth agenesis occurs most frequently in those with complete cleft lip and palate,
unilaterally or bilaterally, and also in those with incomplete bilateral CLP and CP, when
compared with individuals without clefts. The absence of maxillary left lateral incisors is
significantly associated with unilateral right clefts. In contrast, right lateral incisors are most
commonly absent with unilateral left clefts. (8, 17)
1.4.2 Speech pathology
Normal speech requires that the muscles that make up the velopharyngeal sphincter work in a
co-ordinated fashion. Defects in any aspect of the nasopharyngeal anatomy and⁄or physiology
may lead to velopharyngeal incompetence, which is characterized principally by aberrations
in nasality (hyper- or hypo-nasality and nasal air emission). (8)
1.4.3 Craniofacial morphology
The craniofacial morphology is characterized by a prominent premaxilla, a retrognatic maxilla,
reduced posterior maxillary height and a small, retruded mandible. The prolabium is devoid of
any muscle fibers. The nostrils are stretched, and the tip of the nose is broad. The columella
appears to be shortened or nonexistent, and the prolabium often seems to be joined directly to
the tip of the nose. (18)
7
1.4.4 Craniofacial morphology of adult with un-operated BCLP
A prominent premaxilla that causes an overjet ranging from 10 to 16 mm and that
results in a great facial convexity
A small mandible with an extreme clockwise rotation in relation to the cranial base
A smaller mandible with a vertical growth pattern, resulting in an obtuse gonial angle
and a long anterior lower face height
A prominent premaxilla and smaller mandible, resulting in extreme antero-posterior
imbalance between the jaws
A tendency toward retroclination of incisor teeth in both jaws
Smaller dimensions of the cranial basis, but no difference in cranial base angulation
Reduced posterior facial height. (18)
Upper dental arch morphology:
Gender has a differential effect on the maxillary arches of cleft and non-cleft patients;
significant differences are present in non-cleft patients (wider and longer arches in
males), but not in the un-operated patients.
Adult with un-operated BCLP has an anteriorly progressive constriction of the upper
dental arch in both genders and a significantly longer maxillary dental arch, which is
attributed to the premaxillary anterior projection. (19)
1.5 Management of premaxillary protrusion
In early generations the protruded premaxilla in bilateral cleft patients was simply cut away
which leads to a disastrous midfacial hypoplasia. (20) Movement of the protruded premaxilla
was first reported in the 16th century. (21)
When the premaxilla is extremely protrusive, alignment of the three maxillary segments is
necessary. This can be done presurgically, during the operation or postsurgically and the
protruded maxilla can be retracted in an active or passive way.
8
1.5.1 Latham appliance
In 1950 Mc Neil introduced a device to reposition the cleft alveolar segments and Georgiade
and Latham introduced in 1975 a pin-retained appliance, the Latham appliance, to
simultaneously retract the premaxilla and expand the posterior segments over a period of days.
(22)
The Latham appliance is a surgically placed fixed active intraoral device to expand the
maxillary segments and retract a displaced premaxilla without external strapping. It consists
of 2 hard acrylic caps covering the palatal processes joined with a midline screw and an
acrylic labial cap covering the premaxillary fragment. Retraction of the premaxilla is achieved
with power chain. (Figure 2) The parents have to activate the screw on a regular base. The
decrease in the overall length of the palate and retraction of the premaxillary segment
facilitated definitive cleft repair. (13, 23-25)
Figure 2: Latham appliance. The Latham appliance is a surgically placed fixed active intraoral device. It
consists of 2 hard acrylic caps covering the palatal processes joined with a midline screw and an acrylic labial
cap covering the premaxillary fragment. Retraction of the premaxilla is achieved with power chain. (22)
Advantages:
Intercanine width and intertuberosity width increases
The palatal length and intercanine arch length decreases (26)
9
Disadvantages:
Additional costs associated with use of an operating wing and surgeon (26)
Bony fixation with screws or pins could interfere with the developing teeth and the
midfacial growth (22, 26)
Requires general anaesthetics for application of the device (13)
For every millimetre decrease in distance achieved, there is an increase in deviation of
4° of the premaxillary segments relative to the vomer (27)
Patient and parental compliance is not assured (26)
Figure 3: Effect of Latham appliance at three treatment stages. Before preoperative orthopaedics, maxillary
width at the widest aspect of the alveolar arch was 42.3 mm (above). After preoperative orthopaedics, maxillary
width was 49.0 mm (middle). Three months after the primary operation, maxillary width was 43.5 mm (below).
(22)
1.5.2 Passive nasoalveolar moulding appliance (PNAM)
As a reaction to the controversy associated with active retraction of the premaxilla, Hotz
introduced in 1987 the use of a passive orthopaedic plate. In 1993 Grayson described a
technique to correct the alveolus, lip and nose at the same time with a nasoalveolar moulding
appliance. (28)
The passive nasoalveolar moulding (PNAM) appliance is a custom-made plate which reduces
the severity of the initial cleft deformity. It is made of a hard acrylic lined with a thin layer of
soft denture material. When the cleft is reduced to about 5 mm in width, the appliance is
extended with nasal stents to correct the nasal form and lengthen the columella nonsurgically.
10
Also lip taping is used in conjunction with the moulding plate and nasal stents. Nowadays a
large number of modifications are available. (13, 21, 28, 29)
Figure 4: Passive nasolaveolar moulding appliance. The appliance is made of a hard acrylic lined with a thin
layer of soft denture material extended with nasal stents. Also lip taping is used in conjunction with the moulding
plate and nasal stents. (29)
The PNAM appliance gradually applies pressure to the maxillary segments to align the tissues
properly before primary lip and nose repair. This enables the surgeon to achieve a better and
more predictable outcome with less scar tissue formation.
The objective of PNAM includes:
Reducing the width of the alveolar cleft segments until passive contact of the gingival
tissues
Retraction and centring of the premaxilla until contact with the lateral segments
Approximation of the lip segments
Nonsurgical elongation of the columella
Reduction in the width of the nasal tip and the nasal alar base
Improving nasal tip projection (29)
Figure 5: plaster cast at two treatment stages. After treatment with PNAM, there is a reducing of the width of
the alveolar cleft segments until passive contact of the gingival tissues and retraction and centring of the
premaxilla. (21)
11
Advantages
No use of pins and screws
Easier to feed the child with the moulding plate in place
Improves the surgical outcomes of primary repair significantly
Keeps the tongue in a downwards position (25)
Changes in the nasal shape is stable with less scar tissue and better lip and nasal form
(13, 30)
Disadvantages
Parental compliance
Multiple, frequent adjustments are necessary for proper alignment and rotation
Causes irritation of the oral mucosal and gingival tissues and nasal mucosa
The lip tape can cause irritation of the cheeks
Rare risk of airway obstruction
1.5.3 Lip taping
Lip taping is a nonsurgical technique to narrow the cleft at an early phase and improving the
eventual result of definitive lip repair which are the same goals of lip adhesion. The use of
tape strips across the lip segments reduces the deformity by 50% and stretches the lip muscles
and skin surfaces. (21, 31)
Advantages
Very simple and inexpensive procedure
Saves an additional operation
No risk of causing scar tissue to the lip or palate
Definitive lip repair is easier (31)
Disadvantages
Parental compliance
Causes irritation of the cheeks (31)
Time consuming and expensive (13, 28, 32)
12
1.5.4 Lip adhesion
The lip adhesion procedure was first described by Johanson & Ohlsson in 1961, popularized
by Randall in 1965 and used by many others. (33)
Preliminary lip adhesion is the surgical procedure which connects the ends of the lip segments.
Its goal is narrowing the cleft at an early phase and improving the eventual result of definitive
lip repair. (34) An indication for lip adhesion is a wide alveolar cleft with severely
malpositioned maxillary segments, in which primary plasty of the lip and the nose would have
been complicated by this discrepancy. (33) Lip adhesion is mostly performed when the patient
is 3 months old, followed by definitive lip surgery when the patient is 6 to 8 months. (35)
Advantages
Reduces the tension of the primary lip closure
Renders a complete cleft into an incomplete one with a symmetrical nasal platform
Slow moulding of the over expanded lateral palatal and premaxillary segments, which
leads to a narrowing of the anterior and posterior palatal cleft spaces
Moves the cleft lip and palate into a normal position and stabilizes the arch with a
bony bridge to which teeth can be attached
Acts as a dynamic force in aligning the upper alveolar arch (34)
Restores normal muscular function which leads to a reposition of the segments by
natural forces (20)
Disadvantages
Is more expensive than presurgical moulding
Wounds the lip elements
Retracts the premaxilla in an uncontrolled fashion
Does not mould the nasal cartilage (34)
Lack of evidence that the final results of lip repair are better
The risk and expense to the patient of an additional operation
A rate of dehiscence from 5 to 24 %
The possibility of additional internal scarring
Possible sacrifice of tissue needed in lip repair (31)
13
Surgical procedure
Figure 6 shows the lip adhesion procedure according to Millard / Mulliken in patient with a
bilateral cleft lip (A – C). After marking the incision-lines (D and E), the C-flaps within the
prolabial island are designed laterally leaving a philtrum of nearly normal shape and
dimension. The prolabial vermilion remains untouched. Sometimes, especially in patients
with a very wide premaxilla, it is necessary to extend the incision into the nasal vestibulum
along the piriform aperture, to mobilize the alar bases, which has to be positioned on top of
the premaxilla and to be fixed to the anterior nasal spine.
When all edges and all flaps are cut and mobilized (F), the first stage of the repair is to fix the
alar bases onto the premaxilla at the anterior nasal spine. By pulling together the alar bases to
the midline the cleft margins close in the prolabium, so that the vermilion edges can be closed
and form the back of the preliminary lip repair (G). The next step is to insert the C-flaps into
the subalar gap (H and I).
Finally the skin of the lateral lip elements is sutured together with two or three mattress
sutures, which run across the prolabial island. The most cranial cross-suture has to be slung
around the anterior nasal spine (K and L).
There is no need for suture removal because the quality of the scar is irrelevant. It is even
better to leave the sutures, to avoid the slightest risk of wound break down. (20)
14
Figure 6: The surgical procedure of lip adhesion according to Millard in a patient with bilateral cleft lip
and palate (A – C). After marking the incision-lines (D and E), the C-flaps within the prolabial island are
designed laterally leaving a philtrum of nearly normal shape and dimension. When all edges and all flaps are cut
and mobilized (F), the first stage of the repair is to fix the alar bases onto the premaxilla at the anterior nasal
spine. By pulling together the alar bases to the midline the cleft margins close in the prolabium, so that the
vermilion edges can be closed and form the back of the preliminary lip repair (G). The next step is to insert the
C-flaps into the subalar gap (H and I). Finally the skin of the lateral lip elements is sutured together with two or
three mattress sutures, which run across the prolabial island. The most cranial cross-suture has to be slung
around the anterior nasal spine (K and L). (20)
15
The surgical repair of bilateral cleft lip was initially staged with no respect to repair the nose.
This leaded to dissatisfaction with the appearance of the bilateral cleft nasal deformity after
primary labial repair. Some surgeons e.g. Mulliken and Cutting shifted their focus from
secondary to primary nasal repair. This led to new surgical strategies for attaining an ideal
primary nasolabial repair. (13)
1.6 Treatment protocols
The treatment protocol of a patient with bilateral cleft lip and palate differs depending on the
cleft centre. Table 1 describes the dental treatment protocol of the University Hospital in
Ghent and AH Saint Jan in Bruges.
UH Ghent AH Saint Jan Bruges
Nasoalveolar moulding appliance 0-3 months 6 to 8 weeks
Lip adhesion /
Definitive closure of the lip 9 months 3 to 4 months
Definitive closure of the soft palate 1 to 1,5 years
1 year
Definitive closure of the hard palate 4 years
Bonegraft 8 to 11 years 8 to 10 years
Orthodontic treatment (with or
without orthognatic surgery) 11 years and older 11 years and older
Table 1: Dental treatment protocol in UH ghent and AH Saint Jan Bruges
In some surgical centres lip adhesion is used as a standard protocol. However, other surgeons
find the benefits of lip adhesion negligible and don’t apply this technique. Therefore, there’s a
need for a systematic review to see if lip adhesion is an advantage over other therapies such as
PNAM appliance, Latham appliance, etc. The aim of this systematic review is to investigate
the effects of lip adhesion on the maxillary growth of bilateral cleft lip and palate patients.
16
2 Review of the literature
2.1 Material and methods
A PICO was used to specify the present review question in an attempt to identify all relevant
studies:
P (patients with) bilateral cleft lip and palate
I lip adhesion
C no lip adhesion
O 3-dimensional position of the premaxilla in relation to the maxillary lateral
segments
A search strategy was used to identify the articles concerning lip adhesion performed by
patients with bilateral cleft lip and palate. There was no MeSH term available for “lip
adhesion” and “bilateral cleft lip and palate”, so the following search terms were used: “Cleft
Lip”, “Cleft Palate”, “Lip/surgery”, “lip adhesion”, adhesion, Infant, (bilat* OR 2-sid* OR “2
sides” OR “both sides” OR two-sided) and different combinations of these search terms
(Table 4, Table 5 and Table 6). Several electronic databases (Medline, Cochrane and Web of
Science) were searched by two independent investigators (LT and LVQ) for the years 1985
until 2013. The search was restricted to English literature only.
Searching other sources:
Google: search terms are “bilateral cleft lip and palate” AND “lip adhesion”
Reference lists of included studies were screened for further relevant articles.
The titles and abstracts (when available) of all the retrieved papers were screened
independently by the same two investigators in a non-blind fashion. The articles that appeared
to be irrelevant for the research, case reports and duplicates were eliminated.
The inter-reliability between the two investigators was calculated after this first selection for
the Medline database.
17
Afterwards, studies appearing to be relevant, or for which insufficient data existed in the title
or abstract to make a clear decision, the full text was retrieved. A second selection was made
according to the following inclusion criteria.
The reference lists of included studies were screened for further relevant articles.
After the second selection, a quality assessment was completed for every article
independently by the two reviewers and any disagreement on the eligibility of included
studies was resolved through discussion, and by a third review author if necessary.
Table 3: Quality assessment tool
METHOD
Is there a clear study design?
Yes No Unknown
Study design
Duration of the study
Sample size calculation (power)
DEFINITION OF STUDYGROUPS
Is there a clear definition of all study groups?
Yes No Unknown
Setting
Age
Gender
Number
Is there a matched control group?
Inclusion criteria
Exclusion criteria
Inclusion criteria
Bilateral cleft lip and palate
Clinical trial concerning more than 5 patients
Human
Publication date from 1985 to 2013
English
Table 2: inclusion criteria
18
INTERVENTION
Is there a clear definition of the intervention?
Yes No Unknown
Intervention
Control group
OUTCOME
Is there a clear definition of the outcome and is the method of reporting the outcome adequate?
Yes No Unknown
Changes T1-T2 (mm)
Measuring method
Standard deviation
Error of method
Measuring method: on dental casts, radiographic, clinical photographs
BIAS
Risk of bias?
Bias Author’s judgement Support for judgement
Error of method
Blinding
Incomplete outcome data
Selective reporting
Retrospective / prospective
Equipment
Other bias
OVERALL JUDGMENT
Are the results of the study valid and suitable?
19
2.2 Results
2.2.1 Search results
The same filters, publication date from 1985/01/01 to 2012/12/31 and English literature, were
used in al the databases.
95 articles were identified in Medline using the following search term: (“Lip/surgery”[MeSH]
OR “lip adhesion”[tiab] OR adhesion[tiab]) AND (“Cleft Lip”[MeSH] OR “Cleft
Palate”[MeSH] OR “cleft lip” OR “cleft palate”) AND (bilat*[tiab] OR 2-sid*[tiab] OR "2
sides"[tiab] OR "both sides"[tiab] OR two-sided[tiab]). “Infant”[MeSH] was not used in the
search term because of the restriction of the number of articles. ([tiab] = title and abstract)
Table 4: Medline
Search terms Number
#1 "Lip/surgery"[Mesh] 1239
#2 "lip adhesion"[tiab] OR adhesion[tiab] 116804
#3 ("Cleft Lip"[Mesh]) OR "Cleft Palate"[Mesh] OR “cleft lip” OR “cleft
palate” 11604
#4 "Infant"[Mesh:NoExp] 324157
#5 bilat*[tiab] OR 2-sid*[tiab] OR "2 sides"[tiab] OR "both sides"[tiab] OR
two-sided[tiab] 148169
#6 #1 OR #2 124647
#7 #3 AND #6 351
#8 #7 AND #5 95
#9 #8 AND #4 42
20
36 articles were identified in Web of Science using the following search term:
(Topic=(lip/surgery) OR Topic=("lip adhesion") OR Topic=(adhesion)) AND (Topic=(Cleft
Lip) OR Topic=(Cleft Palate)) AND (Topic=(bilat*) OR Topic=(two-sid*) OR Topic=(both
sides) OR Topic=(2-sid*)). Topic=(Infant) was also not used in the search term because of the
restriction of the number of articles.
In the Cochrane Library, one systematic review en 7 clinical trials were found using the
following combination of search terms: (lip/surgery OR "lip adhesion" OR adhesion) AND
(“Cleft Lip” OR “Cleft Palate”) AND (bilat* OR ”two-sided” OR both sides OR “2-sided”).
Table 5: Web of Science
Search terms Number
#1 Topic=(Lip/surgery) 70
#2 Topic=(lip/surgery) OR Topic=("lip adhesion") OR Topic=(adhesion) 231360
#3 Topic=(Cleft Lip) OR Topic=(Cleft Palate) 10664
#4 Topic=(Infant) 213834
#5 Topic=(bilat*) OR Topic=(two-sid*) OR Topic=(both sides) OR Topic=(2-
sid*) 259439
#6 #3 AND #5 1321
#7 #2 AND #3 231
#8 #2 AND #3 AND #5 36
#9 #8 AND #4 10
Table 6: The Cochrane Library
Search terms Review Trials
#1 lip/surgery OR "lip adhesion" OR adhesion 36 2650
#2 “Cleft Lip” OR “Cleft Palate” 7 253
#3 bilat* OR ”two-sided” OR both sides OR “2-sided” 552 23708
#4 “Infant” 774 27906
#5 #2 AND #3 2 31
#6 #1 AND #2 1 19
#7 #1 AND #2 AND #3 1 7
#8 #7 AND #4 1 4
21
2.2.2 Flow diagram of study inclusion
Figure 7: flow diagram. Hundred and thirty-eight articles were found by searching electronic databases and 22
by hand. After reading all titles and abstracts, 40 potentially relevant articles were identified. Seven articles
remained after applying the selection criteria on the full articles. A quality assessment was performed on the
remaining articles and 5 articles were selected for the review.
Electronic search
Medline 95 articles
Web of Science 36 articles
The Cochrane Library 7 articles
Potentially relevant studies identified and
screened for retrieval (after reading all
titles and abstracts)
22 articles
6 articles
Hand search & Google
Hand search of all the reference
lists of the included articles out
of the electronic search
18 articles
1 article
Selection criteria on full articles
7 articles
Quality assessment
5 articles
22
2.2.3 Inter-reliability (Kappa-coefficient)
Medline
LVQ.
LT + -
+ 14 3 17
- 4 72 76
18 75 93
There were 14 articles that were granted by both reader LVQ and reader LT, and 72 articles
that were rejected by both readers. Thus, the observed percentage agreement is Io = (14 + 72) /
93 = 0.92. To calculate the probability of random agreement we note that:
Reader LVQ said "Yes" to 18 articles and "No" to 75 articles. Thus reader LVQ said
"Yes" 19,35% of the time.
Reader LT said "Yes" to 17 articles and "No" to 76 applicants. Thus reader LT said
"Yes" 18,28% of the time.
Therefore the probability that both of them would say "Yes" randomly is 0.19 * 0.18 = 0.03
and the probability that both of them would say "No" is 0.81 * 0.82 = 0.66. Thus the overall
probability of random agreement is Ie = 0.03 + 0.66 = 0.69.
After applying the formula for Cohen's Kappa (
), the inter-observer agreement is
0,74. According to Landis & Koch (1977) this means that there is a substantial agreement.
But there has been noted that this guideline is of little value.
Observed agreement rate (Io) = 0,92
Expected agreement rate (Ie) = 0,69
Kappa (κ) = 0,74
23
2.2.4 Characteristics of excluded studies
Study Reason for exclusion
Bartzela, Katsaros (36) No lip adhesion performed
Berkowitz, Mejia (35) Both groups were treated with lip adhesion
Bitter (20) No primary data, descriptive study
Bitter (25) No primary data, descriptive study
Bitter (37) No primary data, descriptive study
Bitter (38) No primary data, descriptive study
Brogan (39) Only presurgical nasoalveolar moulding, no lip adhesion
performed
Harila, Ylikontiola (40) Prevalence and severity of clefts
Heidbuchel and
Kuijpers-Jagtman (41)
Only presurgical nasoalveolar moulding, no lip adhesion
performed
Heidbuchel, Kuijpers-
Jagtman (42)
Only presurgical nasoalveolar moulding, no lip adhesion
performed
Heidbuchel, Kuijpers-
Jagtman (43)
Only presurgical nasoalveolar moulding, no lip adhesion
performed
Honda, Suzuki (44) No lip adhesion performed
Kim, Kim (45) Different treatments were evaluated together
Liao, Huang (46) No lip adhesion performed
Lisson, Schilke (47) No lip adhesion performed
Marsh and Martin (48) No primary data, descriptive study
Oh (49) Descriptive study about the surgical approach
Opitz and Kratzsch (50) No lip adhesion performed
Penfold and Dominguez-
Gonzalez (51) Review about the surgical approach
Perlyn, Brownstein (52) No primary data, descriptive study
Tindlund and Rygh (53) Orthopedic protraction of the maxilla, no lip adhesion performed
Table 7: characteristics of excluded studies after the second selection
24
2.2.5 Characteristics of included studies
Longitudinal study effects of Hotz’s plate and lip adhesion on maxillary growth in
Bilateral cleft lip and palate patients. Hak, Sasaguri (54)
Effect of lip adhesion on maxillary arch alignment and reduction of a cleft’s width
before definitive cheilognatoplasty in unilateral and bilateral complete cleft lip. Gatti,
Lazzeri (55)
Cleft lip and palate treated by Presurgical orthopaedics, gingivoperiosteoplasty, and
lip adhesion (POPLA) compared with previous lip adhesion method: a preliminary
study of serial dental casts. Millard, Latham (56)
The effect of the lip adhesion procedure on the alveolar arch. With special reference to
the type and width of the cleft and the age at operation. Rintala and Haataja (33)
Effects of lip adhesion and Presurgical orthopaedics on facial growth: an evaluation of
four treatment protocols. Van der Beek, Hoeksma (57)
25
Mea
sure
men
ts
Impre
ssio
n w
ere
taken
under
gen
eral
anes
thes
ia. T
he
wid
th o
f th
e cl
eft
was
mea
sure
d o
n
den
tal
pla
ster
model
s
wit
h a
com
pas
s w
ith
the
tips
poin
ted t
o
the
max
imum
dis
tance
bet
wee
n t
he
alveo
lar
segm
ents
.
The
den
tal
cast
s
wer
e la
bel
ed w
ith
smal
l fl
aps
of
tran
spar
ent
adhes
ive
tape
wit
h b
lack
pin
poin
t m
arks
and
wer
e sc
anned
by a
lase
r 3D
sca
nner
syst
em.
Mea
sure
men
ts w
ere
done
wit
h 3
D-R
ugle
III
soft
war
e.
Con
trol
gro
up
No c
ontr
ol
gro
up
avai
lable
10 5
-yea
r
old
chil
dre
n
wit
hout
clef
ts
Inte
rven
tion
Lip
adhes
ion b
y
Ran
dal
l an
d
Gra
ham
’s
met
hod a
t a
mea
n a
ge
of
44
day
s
Ho
tz’s
pla
te:
pal
atal
pla
te
mad
e of
com
pound s
oft
and h
ard a
cruli
c
resi
n
Lip
adhes
ion
was
per
form
ed
acco
rdin
g t
o
Ran
dal
l (1
965)
Nu
mb
er o
f p
ati
ents
10 p
atie
nts
wit
h
com
ple
te B
CL
P
4 p
atie
nts
wit
h B
CL
wit
h o
ne
side
com
ple
te
and t
he
oth
er
inco
mple
te
53 p
atie
nts
wit
h B
CL
P:
11:
no H
otz
’s p
late
(H
-)
24:
Hotz
’s p
late
(H
+)
18:
Lip
adhes
ion a
nd
Hotz
’s p
late
(L
A-H
)
Age
44 d
ays
(ran
ge
24 –
87
)
LA
: 2 m
onth
s
H:
appli
ed 2
to
3 w
eeks
afte
r
bir
th
Sex
7 M
&
3 F
w
ith
com
ple
te B
CL
P
3 M
& 1
F
wit
h
asym
met
rica
l
BC
L
H-:
8M
& 3
F
H+
: 11M
& 1
3F
LA
-H:
13M
& 5
F
C :
8M
& 2
F
Sel
ecte
d
refe
ren
ces
Gat
ti,
Laz
zeri
(55
),
2010
Hak
,
Sas
aguri
(54),
2012
26
Mea
sure
men
ts
Den
tal
cast
s w
ere
obta
ined
at
ages
3, 6
and 9
yea
rs (
± 6
month
s) a
nd
dif
fere
nt
landm
arks
wer
e dig
itiz
ed.
Anal
ysi
s on d
enta
l
radio
gra
phs
wer
e
also
do
ne.
Photo
gra
phs
and
algin
ate
impre
ssio
ns,
imm
edia
tely
cas
t in
pla
ster
of
Par
is
mould
s, w
ere
taken
pre
oper
ativ
ely, 1 a
nd
4 m
onth
s
post
oper
ativ
ely.
Met
hod o
f
mea
sure
men
ts i
s not
des
crib
ed.
Con
tro
l
gro
up
Lip
adhes
ion
ver
sus
lip
adhes
ion a
nd
pre
surg
ical
ort
hopae
dic
s
No c
ontr
ol
gro
up
avai
lable
Inte
rven
tion
Gro
up I
: su
rgic
al
closu
re o
f th
e so
ft
pal
ate
and l
ip
adhes
ion a
t ag
e 3
month
s
Gro
up I
I: e
last
ic
chai
n p
rem
axil
lary
reposi
tionin
g
appli
ance
and l
ip
adhes
ion
Lip
adhes
ion w
as
per
form
ed u
nder
gen
eral
anes
thes
ia
at t
he
age
of
1 t
o 5
month
s in
one
stag
e on b
oth
sid
es.
The
oper
ativ
e
pro
cedu
re i
s
clea
rly d
escr
ibed
.
Nu
mb
er o
f p
ati
ents
Gro
up I
: 63 p
atie
nts
of
whom
22 B
CL
P
Gro
up I
I: 6
1 p
atie
nts
of
whom
25 B
CL
P
17 p
atie
nts
Age
Gro
up I
: 8y 1
1m
Gro
up I
I: 2
2y 3
m
Age
of
1 t
o 5
month
s
Sex
Unknow
n
No
info
rmat
ion
Sel
ecte
d
refe
ren
ces
Mil
lard
,
Lat
ham
(56),
1999
Rin
tala
and
Haa
taja
(33),
1978
27
Mea
sure
men
ts
Mea
sure
men
ts w
ere
done
on c
eph
alogra
ms
and t
he
dif
fere
nt
landm
arks
wer
e
dig
itiz
ed
Con
trol
gro
up
Contr
ol
gro
up:
lip a
dhes
ion
ver
sus
Hotz
’s
appli
ance
Inte
rven
tion
Lip
adhes
ion
was
per
form
ed
wit
hin
the
firs
t
wee
k a
fter
bir
th
and p
ropose
d b
y
Wal
ker
and
Mei
jer
Nu
mb
er o
f p
ati
ents
28 p
atie
nts
wit
h B
CL
P:
4:
Hotz
’s p
late
; har
d
pal
ate
closu
re a
t 2,5
yea
rs
8:
Hotz
’s p
late
; no
closu
re h
ard p
alat
e
8:
lip a
dhes
ion;
def
init
ive
lip/s
oft
pal
ate
closu
re s
epar
atel
y
8:
Lip
adhes
ion;
repai
r
lip/
soft
pal
ate
sim
ult
aneo
usl
y
Age
Age
rangin
g
from
3 y
ears
and 4
month
s
to f
ou
rtee
n
yea
rs a
nd s
ix
month
s.
Sex
No
info
rmat
ion
Sel
ecte
d
refe
ren
ces
Van
der
Bee
k,
Hoek
sma
(57
),
1992
Ta
ble
8:
cha
ract
eris
tics
of
incl
ud
ed
stu
die
s. T
he
tab
le d
esc
rib
es a
ge,
sex
an
d n
um
ber
of
the
rese
arch
po
pu
lati
on
. In
terv
entt
ion
, co
ntr
ol
gro
up
an
d m
easu
rem
ents
are
also
ex
pla
ined
.
28
2.2.6 Description of included articles
In the study of Gatti et al. (55), 49 patients were treated with lip adhesion, of whom 10
patients had complete bilateral cleft lip and palate and 4 patients had bilateral cleft lip with
one side complete and the other incomplete. All patients were treated in the period between
2000-2007 in the Plastic and Reconstructive Surgery Unit at the hospital of Pisa (Italy). Lip
adhesion was performed by the method of Randall and Graham. The repair was done in one
stage at both sides, in the cases with one side incomplete, lip adhesion was done on the side of
the complete cleft. Afterwards, the clefts were corrected with Mulliken’s cheiloplasty and
bilateral gnathoplasty using Massei’s method at the mean age of 88 days. Impressions of the
maxillary arch were taken under general anaesthesia at the time of lip adhesion and
cheiloplasty. The dental plaster models were examined with a compass and the maximum
distance between the alveolar segments was measured on both sides. There was no control
group available. The population had a Gaussian distribution so a Student’s paired t test was
used to analyse the differences in the width of the clefts before and after lip adhesion.
Figure 8: Reduction in the size of the cleft. The chart illustrates the number of patients as a function of the
reduction of the cleft at the left and right side. (55)
Lip adhesion resulted in a reduction of cleft width of 61% for left-sided clefts and 61% for
right-sided clefts after a mean of 45 days (SD = 13,7). The width of the cleft was reduced with
5,2 (SD = 2,1) and 4,6 mm (SD = 2,5) respectively and this reduction was significant. The
wider side of the cleft was more mouldable than the less severe side, and in cases where the
cleft was symmetrical, lip adhesion gave less effect.
29
So, Gatti et al. concluded that lip adhesion united the soft tissues of the superior lip and
essentially converted a wide complete cleft (generally > 7mm) to an incomplete cleft in
bilateral cleft patients.
In the prospective, longitudinal study of Hak et al. (54) 3 different treatment protocols were
compared mutually long-term and to a control group at the age of 5 years. Fifty-three patients
could be treated, according the specific treatment schedule, at the Cleft Lip and Palate Centre
at the hospital in Jakarta (Indonesia). Of all 53 patients, 24 were treated with a Hotz’s plate (H
(+) group), 11 patients did not receive a Hotz’s plate (H (-) group), whereas 18 patients who
had relatively wider clefts with premaxillary protraction underwent lip adhesion along with a
Hotz’s plate (LA-H group). Impressions were taken at four time points: first visit, at
labioplasty, palatoplasty and 5 years of age.
Figure 9: Landmarks on maxillary arch. The anatomic points were I: papilla insiciva / top of the premaxilla,
A: most dorsal point of the premaxillary contour, C/C’: cuspid points, T/T’: tuberosity points, Pr1: projection of
point I on line CC’ and Pr2: projection of I on line TT’. (54)
The dental casts were labeled with small flaps of transparent adhesive tape with black
pinpoint marks and were scanned by a laser 3D scanner system. Linear and angular
measurements were performed three times and the average values were used for analyses.
Linear measurements were CC’, TT’, I-Pr1 and I-Pr2. The premaxilla angle is formed by the
plane TT’C and AI. Growth rates were also calculated as annual increments (mm/year) of the
linear dimension and the premaxillary angle. The analysis of variance (ANOVA) was used to
compare the average of linear measurements and the growth values among the four groups.
30
The anterior width (CC’) was significantly wider in the LA-H group than in the H (+) group
at labioplasty and at 5 years of age CC’ in all cleft groups was significantly smaller than that
in the non-cleft group. The LA-H and H (-) group showed a significantly wider posterior arch
width (TT’) than the H (+) group at labioplasty. At palatoplasty, TT’ was not different
between the 3 groups. Furthermore, TT’ in the non-cleft group was not significantly different
from that in the three cleft groups. Hak et al. concluded that lip adhesion had temporary
negative effects on the growth of dental arch dimensions, probably synergistically with
labioplasty but this effect became negligible after palatoplasty.
The study of Millard et al. (56) compared the effects of a new treatment protocol (POPLA)
with those of the previous method, lip adhesion alone (group II). POPLA means ‘Presurgical
Orthopaedics followed by Perioplasty and Lip Adhesion’ and this new protocol was
developed in 1978 (group I). At the University of Miami, school of Medicine, 124 patients
were treated. Of these, 22 patients with BCLP belonged to group I (POPLA) and 25 BCLP
patients belonged to group II. In group I, the presurgical orthopaedics was an elastic chain
premaxillary repositioning appliance worn over a period of 3 to 5 weeks. Dental casts were
routinely obtained at birth and at ages 3, 6 and 9 years (± 6 months) and. They were used to
determine the prevalence of anterior and buccal crossbite, to determine the need for a
velopharyngeal flap or a bony graft, and to evaluate the dental arch length and width. X-ray
studies evaluated the bony bridge. After treatment, the alveolar gap was negligible in the
group I patients. Lip adhesion also reduced the alveolar gap but the difference with POPLA
was significant. The incidence of anterior crossbite was higher in group I than in group II at
each age. As age increased, the incidence of anterior crossbite was increased in group I.
However, the anteroposterior distance of the upper arch is continually reduced in group II
after 9 years of age. The incidence of posterior crossbite was less in group I than in group II at
each age because the transverse distance of the upper dental arch was wider in group I than in
group II. Only 30 percent of patients received orthodontic treatment in group I, but this was
69 percent of patients in group II. The incidence of new bony bridge formation was 83.3
percent in group I. The average width of the bony bridge was 2.95 mm and the average bony
height was 7.4 mm. Millard et al. concluded that there was a good alignment of the premaxilla
and the arch form was stable after 16 months when BCLP patients were treated with POLPA.
In group II, the maxillary segments had rotated towards the midline (collapse).
31
At the FCR Cleft Centre in Helsinki (Finland) 102 lip adhesions were performed from 1972 to
1976. A total of 89 cleft patients, of whom 17 bilateral clefts remained for final evaluation.
Rintala et al. (33) used photographs and alginate impressions, who were taken preoperatively
and 1 and 4 months postoperatively. The width of the cleft, segmental deviation and the
premaxillary protrusion were measured on dental plaster models. Width of the cleft was
defined as the shortest distance between the lateral maxillary segments and the premaxilla,
and premaxillary protrusion is the sagittal distance of the premaxilla to the lateral segments.
Segmental deviation was considered as positive when the lateral segment was outside an
imaginary corresponding normal arch and negative when it was inside this normal arch. The
material was divided into two groups (2 and 4 months) to evaluate the influence of the age at
operation. The width of the cleft was decreased approximately 40 – 50% more on the wider
side but there was an explicit individual variation. The segmental deviation was always
negative and diminished by approximately 40% on average. The protrusion of the premaxilla
diminished only about 8-23 %, with very wide individual variations. In patients, operated at
an earlier age there was an insignificantly better effect upon both width of the cleft and
segmental deviation.
To compare the effects of lip adhesion and presurgical orthopaedics on facial growth, Van
der Beek et al. (57) used four different treatment protocols. Twenty-six Dutch children were
treated with preoperative orthopaedics (Hotz’s appliance) at the Academic centre for
Dentistry in Amsterdam and were divided into 2 groups. Group I consisted of children who
had hard palate closure at 2,5 years, while the children in group II still needed the hard palate
to be closed. At Saint Barbara’s Medical Centre in New Jersey, 35 American children
underwent lip adhesion within the first week of life. They were also divided into two groups.
Group III consisted of children for whom the definitive lip and soft palate repair were done
separately, in group IV this was done simultaneously. Different landmarks were digitized on
the cephalograms and measurements were done to evaluate the maxilla, mandibula and the
relation between both. Differences between the four groups were tested after adjusting the
measurements for age and for timing of lip and palate closure if appropriate. The relative
length of the maxilla (PNS-ANS), after correcting for chronological age and for the age at
definitive lip and soft palate repair, was significant different for the four operation schemes.
SNA was larger for operation schemes I, II and III, while the reverse was true for group IV.
32
The relative length of the mandibula (Po-Go) was 64% for patients treated with lip adhesion
and 72% for those treated with a Hotz’s appliance. There were no significant differences
between the four groups regarding the relation between the maxilla and mandibula
(AB/occlusal plane). Van der Beek concluded that mean maxillary lengths were generally
larger for individuals who received Hotz’s appliance than for those who received lip adhesion.
Figure 10: Landmarks on cepfhalogram. The following landmarks were digitized for the maxilla: ANS, PNS,
A and for the mandibula: B, Po, Gn, M and Go. (57)
33
3 Discussion
Lip adhesion received a lot of criticism in the past. The opponents assumed that lip adhesion
caused more tension on the premaxilla and maxillary segments with a higher risk of collapse
and scar tissue. In most cases, lip adhesion could not replace presurgical orthopaedics, and
was most effective on small clefts. The effect on nasoalveolar tissue was not yet demonstrated.
They suggested that young children should not be exposed to an additional surgical treatment.
(58) On the other hand, the advocates concluded that lip adhesion converted a complete wide
cleft lip to an incomplete cleft with better position of the maxillary segments and premaxilla.
(55, 59)
Lip adhesion resulted in a reduction of the width of the cleft at both sides, but Rintala and
Haataja found approximately 40 à 50% more reduction at the most severe side. (33) This was
confirmed by Gatti et al. who found that the wider side of the cleft was more mouldable than
the less severe side. In cases where the cleft was symmetrical, lip adhesion gave less effect.
(55) Rintala and Haataja were disappointed by the relatively modest effect of lip adhesion in
patients with a heavily protruded premaxilla. Simultaneous widening of the collapsed lateral
segments by an orthodontic plate is necessary to produce space for the protruded premaxilla.
(33)
Rintala and Haataja (33) evaluated the influence of the age at operation and divided the
material into two groups. The first group was treated with lip adhesion at 2 months of age, the
second one when the patients were 4 months old. In patients who were operated at 2 months
old, an insignificantly better effect was found upon both the width of the cleft and the
segmental deviation, but not upon the maxillary protrusion. Gatti et al. (55) concluded that the
younger the patient was at lip adhesion, the faster it took for the maxillary segments to mould
themselves.
For children treated with preoperative orthopaedics compared to lip adhesion, the length of
the maxilla was longer. Ross and MacNemara (60) indicated that presurgical orthopaedics
does not have any influence on facial growth and development, so in the study of Van der
Beek et al. (57) the smaller maxillary length could have been induced by the early lip
adhesion procedure. When lip adhesion in combination with a Hotz’s appliance is compared
to a Hotz’s appliance only, Hak et al. (54) found that the anterior and posterior width of the
34
maxilla was significantly wider at the first visit and at labioplasty at age 4 months. This might
be attributed to the selection of patients with a wider cleft and a greater premaxillary
protrusion in the LA-H group. The selection was not randomized and the results could be
easily influenced by this selection bias. They concluded that lip adhesion had a temporary
negative effect on the growth of dental arch dimensions. This could be explained by a smaller
growth rate of I-Pr2 and a greater growth rate of the premaxillary angle in LA-H group than in
the H (+) group between the first visit and labioplasty.
Millard et al. (56) compared the effects on maxillary arch and dental occlusion of BCLP
patients treated with a new technique (POPLA, presurgical orthopaedics and lip adhesion)
to a previous lip adhesion method. They concluded that the incidence of anterior crossbite was
higher in the POPLA group, but the incidence of posterior crossbite was lower. Less posterior
crossbite could be explained by the increase of the intercuspid width between 3 and 9 years of
age in group POPLA. However, in the lip adhesion group, they observed an increase of the
dental arch width at deciduous molars and permanent first molars, while group POPLA
patients failed to show any increase in dental arch width. The conclusion about the anterior
and buccal crossbite in group POPLA should be interpreted with caution due to the small
sample. Only 8 out of 22 patients remained for follow-up. When age increased, the incidence
of anterior crossbite also increased in group POPLA. In comparison with the POPLA group,
the patients treated with lip adhesion only showed a rotation of the maxillary segments to the
midline. This collapse was not observed in the patients treated with POPLA due to the support
of the maxillary segments by the presurgical orthopaedics. In many cases simultaneously
widening of the collapsed lateral segment by an orthodontic plate is necessary in order to
produce space for retruding the premaxilla. Cho (34) used the same technique to achieve a
normal position and stabilise the arch in a symmetrical platform. However, presurgical
orthopaedics have not been shown to improve the surgical aspect of lip repair at this time, and
more well-controlled studies are required.
Perlyn, Brownstein (52) the correlation between initially maxillary arch dysmorphology in
BCLP patients and the occlusal relationship in early mixed dentition. In early mixed
dentition, approximately three-fourths of patients with complete BCLP had favorable
occlusion and one-fourth unfavorable occlusion. The occlusal status seemed unrelated to the
initial maxillary arch dismorphology, the use of early passive alveolar moulding appliance, or
35
surgical premaxillary setback. Berkowitz, Mejia (35) found that the frequency of anterior and
buccal crossbite was significantly higher in patients with BCLP who were treated with
presurgical orthopaedics, ginivoperiostoplasy and lip adhesion compared to those treated with
nonpresurgical orthopaedics only.
When the effect of lip adhesion in bilateral cleft lip patients are compared with those in
unilateral clefts, Rintala et al. (33) concluded that the effect upon the width of the bilateral
cleft was clearly less significant than in the unilateral ones and the individual variations were
more pronounced. Unlike that study, Gatti et al. (55) achieved almost the same reduction in
the width of the cleft. This could be explained by the younger age at lip adhesion that they
studied, as the maxillary segments were better moulded. The study of Van der Beek et al. (57)
found that the maxillary length was generally larger for children with a bilateral cleft lip, but
the angle between the upper incisors and the spinal plane was significantly lower. SNA was
larger for bilateral clefts for group I, II and III and the reverse was true for group IV. There
was a significant difference in the position of the mandible and the maxilla relative to the
occlusal plane between the cleft type, but no significant differences were found in the
mandibular length..
Due to the small number of articles found in this review, no powerful conclusion can be made.
There is a high need for prospective randomized clinical trials about lip adhesion in patients
with bilateral cleft lip and palate.
36
4 Conclusion of the review
Lip adhesion unites the soft tissues of the superior lip and converts a wide complete cleft to an
incomplete cleft in bilateral cleft patients. Lip adhesion gives a better alignment of the
premaxilla with the lateral maxillary segments. The most effect is seen on the wider side of
the cleft and when the operation is performed at a younger age. It’s advisable to combine lip
adhesion with a passive moulding appliance to achieve a normal position and maintain a
stable arch form and to avoid an inwards rotation of the maxillary segments. One article
mentions that lip adhesion had temporary negative effects on the growth of dental arch
dimensions, probably synergistically with labioplasty, but this effect became negligible after
palatoplasty.
37
5 Pilot study
In the past, most research about lip adhesion in bilateral cleft lip and palate patients was done
from an ooclusal point of view. No authors paid attention to the vertical aspect of the
premaxilla and the lateral maxillary segments. There is reason to assume that the vertical
dimension between the premaxilla and the lateral segments changes when lip adhesion and/or
presurgical orthopaedics is used. This pilot study explains the protocol and measuring method
for future research. A first try-out of the measuring method was done on anonymous existing
records.
5.1 Protocol for future research
5.1.1 Aim
The purpose is to compare the effects of lip adhesion with preoperative orthopaedics sc. a
passive nasoalveolar moulding appliance on the vertical dimensions of the premaxilla and
lateral maxillary segments of bilateral cleft lip and palate patients.
5.1.2 Null hypothesis
There is no difference in the vertical position of the premaxilla in bilateral cleft patients after
lip adhesion compared with presurgical orthopaedics.
5.1.3 Method
Study design
The standard method to test the efficacy and/or effectiveness of various types of medical
interventions within a patient population is a RCT aka Randomized Controlled (Clinical) Trial.
Randomization eliminates bias in treatment assignment, specifically selection bias and
confounding. But randomization is not always possible in cleft patients because every
treatment has specific indications and both parents and surgeons want the best solution for the
child. The study needs to be a prospective blinded Randomized Clinical Trial. Prospective
research is recommended to assure proper data gathering and to exclude bias. Blinded means
that both surgeons, patients and researchers don’t know which treatment a patient underwent.
38
Sample size calculation
It is important to consider the statistical power of a hypothesis test when interpreting its
results. A test's power is the probability of correctly rejecting the null hypothesis when it is
false; a test's power is influenced by the choice of significance level for the test, the size of the
effect being measured, and the amount of data available. A hypothesis test may fail to reject
the null, for example, if a true difference exists between two populations being compared by a
t-test but the effect is small and the sample size is too small to distinguish the effect from
random chance. (61)
Data collection
Impressions of the maxillary arch in bilateral cleft patients were made at the time of lip
adhesion or presurgical orthopaedics and at cheiloplasty. All plaster study models date from
1999 to 2008 and were scanned by an industrial CT scanner in a lab in the Netherlands. The
maxillary landmarks were digitized with Geomagic Qualify® 12 Software by one researcher
(LVQ). In total, 16 plaster models of the maxillary arch in bilateral cleft patients treated with
lip adhesion were available for this pilot study.
In the future, impressions of the maxillary arch should be made with AlgiNote, a alternative
impression material. In the different cleft centres there is also need for compatible data
collection to secure further research. The following scheme (Table 9) shows the
recommendations of the WHO regarding the data collection in cleft patients.
Timing Casts Cephalogram Clinical
photographs Speech Audiometry Questionnaire
Primary
surgery ✔ ✔
3 years ✔* ✔*
5/6 years ✔ ✔ ✔ ✔
10 years ✔ ✔ ✔ ✔ ✔
+18 years ✔ ✔ ✔ ✔ ✔
Table 9: recommendation of the WHO regarding the data collection in cleft patients.
(* when the hard palate is closed)
39
Landmarks
Landmarks on the maxillary arch
I Incisal point Intersection of the crest of the alveolar ridge and the line
drawn from the labial frenulum to the incisive papilla
P/P’ Cleft edge points of the
premaxilla
Cleft edges of the crest of the alveolar ridge of the
premaxilla
C/C’ Cuspid points Intersection point of the distal canine sulcus and the
alveolar ridge line
A/A’ Alveolar ridge point Point on top of the alveolar ridge (lateral view of the
model)
Table 10: Reference points in the maxillary arch of patients with BCLP
Figure 11: Landmarks on maxillary arch. Different landmarks were digitized on the maxillary arch. I, P and P’
on the premaxilla stand for incisal point, cleft edge point on the premaxilla right and left resp. On the maxillary
segments cuspid point right and left were digitized and A and A’ represent the top of the alveolar ridge right and
left resp.
An average plane was created using 2 lines through (C and A’) and (C’ and A) (Figure 11).
This plane was referred to as XY in the co-ordinate system with C set as origin and the x-axis
according to the direction of CC’(Figure 12).
Y
X
40
Figure 12: co-ordinate system in Geomagic Qualify® 12. An average plane was created using 2 lines
through (C and A’) and (C’ and A). This plane was referred to as XY in the co-ordinate
system with C set as origin and the x-axis according to the direction of CC’.
Measurements
Points coordinates X Y Z
I / plane
Transversal position
of I, P and P’
Sagittal position
of I, P and P’
Vertical position
of I, P and P’ P / plane
P’ / plane
The measurements (in mm) were done to evaluate the changes of the premaxilla in the
transversal, sagittal en vertical dimensions in children treated with lip adhesion and/or
presurgical orthopaedics. (Geomagic Qualify® 12)
41
5.1.4 Statistical analysis
For assessment of the combined method error in locating and measuring the changes of the
different landmarks, 10 randomly selected casts were again denoted and re-measured by the
same researcher after 2 months. The following formula was used for the method error
calculation: formula of Dahlberg ( √∑
) where d is the difference between two
measurements of a pair and n is the number of double measurements.
The SPSS (Statistical Package for the Social Sciences, SPSS Inc. 20, Chicago, IL) for
Windows 7 Software package was used for the statistical analysis of the data.
The Students paired t-test was used to compare the differences between T1 and T2 for the
different measurements, because it was possible to guarantee normal distribution. The
population was distributed Gaussian according to the test of normality by Shapiro and Wilk.
The results were assessed in 95% confidence intervals and considered significant when
p < 0.05.
In the results, the following shortenings were used to describe the statistical results.
* < 0.05 (marginal significant)
** < 0.01 (significant)
*** < 0.001 (high significant)
ns not significant
42
5.2 Results
5.2.1 Error of the method
The highest error of method (Table 11) was found in the vertical measurements (mean 0,60).
Overall, the error of method was relatively small ranging from 0,20 to 0,64 mm with a mean
of 0,43 mm. Brief et al. (62) investigated the intra- and interobserver error for landmark
positioning on digitized casts of patients with unilateral cleft lip and palate. They concluded
that the error of method was 0.34 to 1.30 mm for the intraobserver investigation. Most authors
accepted an error of method of 0,8 mm (63). But there was no gold standard and the error of
method must be examined depending on the outcome of the measurements. Literature also
proved that there’s a learning curve and that the error of method decreased with routine.
The measuring method used in this pilot study results in an error of method within the limits
described in the literature. So this technique can be used in future research.
Measurement
(mm) ME
Ix 0.56
Iy 0.35
Iz 0.60
Px 0.28
Py 0.21
Pz 0.64
P’x 0.46
P’y 0.20
P’z 0.57
Table 11: Error of method (ME) for the different measurements. The highest error of method was found in
the vertical measurements (mean 0,60). Overall, the error of method was relatively small ranging from 0,20 to
0,64 mm with a mean of 0,43 mm.
43
5.2.2 Vertical changes of the premaxilla (z-value)
Lip adhesion
T1 T2 T2-T1
I 0.82 (2.72) 1.88 (2.75) 1.06 (3.27)ns
P -4.05 (3.64) -2.27 (2.41) 1.78 (3.43)ns
P’ -3.66 (2.85) -1.98 (2.60) 1.68 (3.98)ns
Table 12: Vertical changes in mm (SD).
There were no statistically significant differences in the vertical position of the premaxilla
before and after lip adhesion. The vertical movement of all three points amounted to 1 mm
and the results were both statistically and clinically not relevant.
Figure 13, Figure 14 and Figure 15 are box-and-whisker plots and illustrate the insignificant
differences in vertical position of point I (Iz), P (Pz) and P’ (P’z) respectively before and after
lip adhesion. The box itself represents the middle 50% of all data and the thick line represents
the median. Twenty-five percent of the data is below the lower boundary of the box and 75%
is above the upper boundary. The whiskers represent the greatest and least value excluding the
outliers.
Figure 13: Vertical position of the incisal point before and after lip adhesion. No significant difference was
found in the position of the incisal point of the premaxilla.
Iz
T1
T2
44
Figure 14: Vertical position of point P before and after lip adhesion. No significant difference was found in
the position of the right cleft edge of the premaxilla.
Figure 15: Vertical position of point P' before and after lip adhesion. No significant difference was found in
the position of the left cleft edge of the premaxilla.
Pz
P’z
T1
T1
T2
T2
45
5.2.3 Sagittal changes of the premaxilla (y-value)
Lip adhesion
T1 T2 T2-T1
I 15.83 (2.50) 12.47 (2.89) -3.36 (2.63)***
P 12.45 (3.62) 9.29 (3.88) -3.17 (3.28)**
P’ 13.38 (4.34) 9.96 (3.06) -3.42 (4.65)**
Table 13: Sagittal changes in mm (SD).
In patients treated with lip adhesion, all three points moved significantly backwards in the
direction of the co-ordinate system. This means there was a significant reduction of the width
of the alveolar cleft at both sides and the premaxilla was aligned in between the maxillary
segments. I, P and P’ moved backwards in equal proportions which indicated a paralell
movement with no rotation. These results were confirmed by the previous research on the
same population. (64)
5.2.4 Transversal changes of the premaxilla (x-value)
Lip adhesion
T1 T2 T2-T1
I 13.90 (5.86) 14.75 (4.75) 0.85 (5.75)ns
P 6.67 (5.21) 5.79 (3.76) -0.88 (4.90)ns
P’ 23.69 (6.52) 23.29 (5.52) 0.24 (5.68)ns
Table 14: transversal changes in mm (SD).
There were no statistically significant differences in the transversal position of the premaxilla
before and after lip adhesion These results were also confirmed by the previous research on
the same population. (64)
46
5.3 Discussion
Nowadays, impressions of the maxillary arch in patient with clefts are made with AlgiNote
FS. Nassar, Hussein (65) investigated the dimensional accuracy and stability of this
alternative impression material with immediate and delayed pouring and compared it to a
traditional irreversible hydrocolloid material. With immediate pouring, AlgiNote exhibited
minimal dimensional changes, which were maintained or reduced with 4-hour pouring. For
both pouring times, these changes were less than 0.5%. In the past, different types of materials
like VPS impression materials were used to make the dental casts. Katyayan, Kalavathy (66)
found that the dimensional changes for 2 different VPS materials were well within ADA
standards of minimal shrinkage value of 0.5% under wet and dry conditions. Therefore, it can
be accepted that the shrinkage of the impression material in the pilot study is negligible when
assumed that the materials were handled under the right conditions.
In the literature, three-dimensional virtual models of neonatal cast models of BCLP patients
can be used reliably and validly to perform linear measurements between existing reference
points on the surface of the model. (67) However, Abizadeh et al (68) decided that digital
study models have a role for clinical applications although cannot yet replace other current
methods for scientific research. On the other hand, Sousa, Vasconcelos (69) found that
measurements of arch width and length on digitized models showed high accuracy and can be
used for research with satisfactory degrees of accuracy and reproducibility. Santoro et al. (70)
concluded that since the shrinkage was uniform the diagnostic capacity of the software is not
affected, especially when comparing proportional measurements. In this pilot study, data is
compared before and after a certain therapy, so there could be assumed that the error of
method was equal and therefore negligible.
Geomagic Qualify® 12 was used instead of the software that comes with the scanner
(Digimodel), although Naidu, Scott (71) found a good validity and an excellent reliability and
reproducibility of Digimodel. But it is impossible to determine the vertical distance between a
point and the occlusal plane with Digimodel.
47
The error of the measurements in this pilot study was between 0,20 en 0,64 mm. The
highest error of method was found in the vertical measurements. This might be attributed to
the difficulty to set the vertical position of point P and P’. When the data were interpreted, the
error of method was taken into account.
The vertical movements of the premaxilla were very small and statistically not significant in
patients treated with lip adhesion. Position of the incisal point was before and after therapy
near the occlusal plane. In the literature, no research was performed on the vertical position of
the premaxilla so no comparison could be made. There is a high need for prospective clinical
trial about the vertical aspects of treatment in patients with bilateral cleft lip and palate.
In patients treated with lip adhesion, the protrusion of the premaxilla diminished about 8 to 23
percent according to Rintala. (33) In the present study the sagittal results showed a retraction
of the premaxilla about 3 mm. The significant retraction of the premaxilla after lip adhesion
could be explained by the higher tension on the premaxilla when lip adhesion was done.
There were no statistically significant differences in the transversal position of the
premaxilla before and after lip adhesion.
Previous research at our University (64) investigated the effect of lip adhesion and PNAM
on the maxillary growth within the same population. The patients treated with lip adhesion
showed a significant reduction in width of the alveolar cleft at both sides and in proposition of
the premaxilla. These results were confirmed by the present study and also showed by other
authors like Rintala and Haataja (33), Gatti, Lazzeri (55). This study also concluded that there
was a significant increase in width of the premaxilla, decrease in width of the palatal cleft
and a significant increase in the most ventral width of the lateral segments. Those who were
treated with a nasoalveolar moulding appliance only showed a significant reduction in width
of the cleft at the left side and a significant increase in width of the premaxilla. When the two
treatments were compared, they concluded that patients treated with lip adhesion showed a
significant higher reduction in width of the alveolar cleft only at the right side. At the left side,
no significant differences were found. They also decided that there was a not statistical
significant increase in width of the lateral maxillary segments in patients treated with the
moulding appliance, while those who were treated with lip adhesion showed a not significant
decrease of these distances.
48
The conclusions about the present study should be interpreted with caution due to a small
sample size. There is a high need for prospective clinical trial about the vertical aspects of
treatment in patients with bilateral cleft lip and palate. Randomization is not always possible
and might be defined as morally irresponsible.
49
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7 Attachments
7.1 Attachment 1: Quality assessment included articles
7.1.1 Hak, Sasaguri (54)
Longitudinal study effects of Hotz’s plate and lip adhesion on maxillary growth in Bilateral
cleft lip and palate patients.
METHOD
Is there a clear study design? YES
Yes No Unknown
Study design Prospective longitudinal
study
Duration of the study 2000 – 2005
Sample size calculation (power) 57,1%
DEFINITION OF STUDYGROUPS
Is there a clear definition of all study groups? YES
Yes No Unknown
Setting CLP centre, Jakarta,
Indonesia
Age 2 months
Gender H-: 8M & 3F
H+: 11M & 13F
LA-H: 13M & 5F
C : 8M & 2F
Number 53 patients
Is there a matched control group? Control
group
was not
matched
Inclusion criteria Patients treated according
the treatment shedule
Exclusion criteria Simonart’s band and
syndromes
INTERVENTION
Is there a clear definition of the intervention? YES
Yes No Unknown
Intervention Hotz’s plate versus lip
adhesion
Control group 10 5 year old children with
no cleft
OUTCOME
Is there a clear definition of the outcome and is the method of reporting the outcome adequate?
YES
Yes No Unknown
Changes T1-T2 Were measured in mm
Measuring method On dental casts
Standard deviation Always mentioned
Error of method Measurements were done
twice and the mean was
used
Measuring method: on dental casts, radiographic, clinical photographs
BIAS
Risk of bias? Moderate
Bias Author’s judgement Support for judgement
Blinding Lip adhesion was done by
patients with a cleft >
7mm
Incomplete outcome data Unknown
Selective reporting Unknown
Retrospective / prospective Prospective
Equipment Clearly described
Other bias /
7.1.2 Gatti, Lazzeri (55)
Effect of lip adhesion on maxillary arch alignment and reduction of a cleft’s width before
definitive cheilognatoplasty in unilateral and bilateral complete cleft lip.
METHOD
Is there a clear study design? YES
Yes No Unknown
Study design Clinical trial
Duration of the study 2000 - 2007
Sample size calculation (power) ✔
DEFINITION OF STUDYGROUPS
Is there a clear definition of all study groups? YES, but no control group available
Yes No Unknown
Setting Pisa, Italy
Age 44 days (24 – 87)
Gender Complete cleft: 3 females,
7 males
Incomplete cleft: 1 female,
3 males
Number 14 patients
Is there a matched control group? ✔
Inclusion criteria Cleft > 7mm
Malposition maxillary
segments
Severe protrusion of the
premaxilla
Exclusion criteria ✔
INTERVENTION
Is there a clear definition of the intervention? YES
Yes No Unknown
Intervention LA: Randall and Graham’s
method (44days)
CG: Tennison’s technique
modified by Massei (102
days)
P: Veau-Wardill-Nylen
palatoplasty (5 to 6 months)
Control group ✔
OUTCOME
Is there a clear definition of the outcome and is the method of reporting the outcome adequate?
YES
Yes No Unknown
Changes T1-T2 (mm) Expressed in mm and
percents
Measuring method On dental plaster casts (LA
and CG) with a calliper
Standard deviation Always mentioned
Error of method ✔
Measuring method: on dental casts, radiographic, clinical photographs (were taken at LA,
GC and several months later)
BIAS
Risk of bias? Was not taken into account
Bias Author’s judgement Support for judgement
Blinding Could not be done Ethical not possible
Incomplete outcome data Unknown
Selective reporting Unknown
Retrospective / prospective Retrospective
Equipment Shortcoming about
impression material, etc were
not mentioned
Other bias /
7.1.3 Millard, Latham (56)
Cleft lip and palate treated by Presurgical orthopedics, gingivoperiosteoplasty, and lip
adhesion (POPLA) compared with previous lip adhesion method: a preliminary study of
serial dental casts.
METHOD
Is there a clear study design? YES
Yes No Unknown
Study design Retrospective clinical trial
Duration of the study 1983 – present
Sample size calculation (power) ✔
DEFINITION OF STUDYGROUPS
Is there a clear definition of all study groups? YES
Yes No Unknown
Setting University of Miami, school
of Medicine
Age Group I: 8y and 11 months
Group II: 22y and 3 months
Gender ✔
Number Group I: 63 (22 BCLP)
Group II: 61 (25 BCLP)
Is there a matched control group? Lip adhesion without
orthopaedics
Inclusion criteria ✔
Exclusion criteria ✔
INTERVENTION
Is there a clear definition of the intervention? YES
Yes No Unknown
Intervention Lip adhesion and presurgical
orthopaedics
Control group Lip adhesion without
orthopaedics
OUTCOME
Is there a clear definition of the outcome and is the method of reporting the outcome adequate?
YES
Yes No Unknown
Changes T1-T2 (mm) ✔
Measuring method On dental casts and X-rays
Standard deviation ✔
Error of method Not performed
Measuring method: on dental casts, radiographic, clinical photographs
BIAS
Risk of bias? Moderate
Bias Author’s judgement Support for judgement
Blinding Could not be done Ethical not possible
Incomplete outcome data High drop-out because of
follow-up but patients
were initially not included
in study
Selective reporting Unknown
Retrospective / prospective Retrospective
Equipment Shortcoming about
impression material, etc
were not mentioned
Other bias /
7.1.4 Rintala and Haataja (33)
The effect of the lip adhesion procedure on the alveolar arch. With special reference to the
type and width of the cleft and the age at operation.
METHOD
Is there a clear study design? YES
Yes No Unknown
Study design Clinical trial
Duration of the study Patients were followed until 4
months postoperative
Sample size calculation (power) ✔
DEFINITION OF STUDYGROUPS
Is there a clear definition of all study groups? YES
Yes No Unknown
Setting FCR cleft centre
Age LA: 1 to 5 months
Gender ✔
Number 89 patients (17 with BCLP)
Is there a matched control group? ✔
Inclusion criteria Wide alveolar cleft with
severely malpositioned
maxillary segments
Exclusion criteria Dehiscence and lack of
information
INTERVENTION
Is there a clear definition of the intervention? YES
Yes No Unknown
Intervention The operative procedure of
lip adhesion is clearly
described.
Control group ✔
OUTCOME
Is there a clear definition of the outcome and is the method of reporting the outcome adequate?
Moderate
Yes No Unknown
Changes T1-T2 (mm) Results showed on graphs,
not expressed in mms
Measuring method On plaster models
Standard deviation Showed in graphs but not
clear
Error of method ✔
Measuring method: on dental casts, radiographic, clinical photographs
BIAS
Risk of bias? Moderate
Bias Author’s judgement Support for judgement
Blinding Could not be done Ethical not possible
Incomplete outcome data Unknown
Selective reporting Unknown
Retrospective / prospective Retrospective
Equipment Impressions were
immediatly cast in plaster
Other bias /
7.1.5 Van der Beek, Hoeksma (57)
Effects of lip adhesion and Presurgical orthopaedics on facial growth: an evaluation of four
treatment protocols.
METHOD
Is there a clear study design?
Yes No Unknown
Study design Retrospective clinical trial
Duration of the study ✔
Sample size calculation (power) ✔
DEFINITION OF STUDYGROUPS
Is there a clear definition of all study groups? YES
Yes No Unknown
Setting The Netherlands versus
USA
Age Ranging from 3y and 4 m to
14y and 6m
Gender ✔
Number Group I: 4 patients
Group II/III/IV 8 patients
Is there a matched control group? Hotz’s appliance versus lip
adhesion
Inclusion criteria Similar treatment
Exclusion criteria ✔
INTERVENTION
Is there a clear definition of the intervention? YES
Yes No Unknown
Intervention The operative procedure of
lip adhesion is clearly
described.
Control group Hotz’s plate
OUTCOME
Is there a clear definition of the outcome and is the method of reporting the outcome adequate?
Yes No Unknown
Changes T1-T2 (mm) Expressed in percentages;
figures in mms
Measuring method Clearly described
Standard deviation ✔
Error of method Percentage of the distance
N-Me / BA-N
Measuring method: on dental casts, radiographic, clinical photographs
BIAS
Risk of bias?
Bias Author’s judgement Support for judgement
Blinding Could not be done Ethical not possible
Incomplete outcome data Unknown
Selective reporting Unknown
Retrospective / prospective Retrospective
Equipment Unknown
Other bias /
7.2 Attachment 2: License agreement (Elsevier)
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Licensed content title Repair of bilateral clefts of lip,
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Licensed content author Klaus Bitter
Licensed content date February 2001
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