Is Cleft Severity Related to Maxillary Growth in Patients with Unilateral Cleft Lip and Palate?

Abstract

Objective

To study the relationship of cleft severity and maxillary growth in patients with unilateral cleft lip and palate.

Design

A systematic literature review.

Methods

A literature survey from the PubMed database from January 1966 to December 2008 used the Medical Subject Headings terms facial growth, unilateral cleft lip palate, cephalometry, and cleft severity or cleft width. The Cleft Palate–Craniofacial Journal from 1964 to November 2008 was hand searched. Studies published as full-length articles reporting quantitative data on the relationship of cleft severity and written in English were selected. Two reviewers selected and extracted the data independently and also assessed the quality of the studies.

Results

Four studies met the selection criteria and were included in the review. All were retrospective and longitudinal. Quality analysis revealed medium to low level of the included studies. Heterogeneity of the studies prevented major conclusions about the relationship of a severe cleft and unfavorable maxillary forward growth.

Conclusions

The review has highlighted the importance of further research. Further well-designed controlled studies and long-term studies are needed, and researchers have to consider combined assessment of cleft size and palate size. Further studies should also focus on the cleft severity at birth and at the time of palate repair.

Keywords

cleft severity maxillary growth maxillary morphology unilateral cleft lip and palate

Midface retrusion is often seen in patients with repaired unilateral cleft lip and palate (UCLP). Two factors have been suggested to influence the growth deficiency (Ross, 1987). One such factor is the intrinsic factor, including developmental deficiency leading to the formation of a cleft and the growth potential of midfacial skeleton. The other factor is the iatrogenic factor, mainly introduced by surgical repair. The influence of surgical repair of the lip and palate has been the focus of many studies (Ross, 1987; Williams and Sandy, 2003; Liao and Mars, 2005a, 2005b; Liao et al., 2006). However, the degree of midface retrusion differs in patients with UCLP, even when the same surgeon has performed the uniform surgical procedures. This suggests that cleft severity may play a role in the later growth of the maxilla.

Cleft severity is usually evaluated from its appearance at birth. Initial cleft severity in patients with UCLP varies. This is reflected in the sizes of the cleft and the palate. Only a few studies have been published on the relationship of maxillary growth (Suzuki et al., 1993; Peltomaki et al., 2001; Honda et al., 2002; Nakamura et al., 2005). Peltomaki et al. (2001) reported that patients with a small cleft have better maxillary forward growth when compared with those with a large cleft. However, the bulk of the literature suggests that presurgical infant orthopedics that is able to reduce the cleft size has no bearing on later growth of the maxilla (Ross, 1987; Chan et al., 2003; Bongaarts et al., 2004, 2006). To study the relationship of cleft severity and maxillary growth in patients with UCLP, a systematic review was undertaken with special focus on maxillary length, height, width, and protrusion. We aimed to answer the following questions: In patients with UCLP, is cleft severity related to later growth of the maxilla? Is a severe cleft related to unfavorable maxillary forward growth? Furthermore, a quality analysis of the methodological soundness of the studies in the review was performed.

Methods

Search Strategy

To identify all studies that examined the relationship of cleft severity and maxillary growth, a literature survey was performed using the following criteria: (1) the Medline database (EntrezPubMed, www.ncbi.nim.nih.gov) from January 1966 to December 2008 was searched using the Medical Subject Headings terms maxillary growth, unilateral cleft lip palate, cephalometry, and cleft severity or cleft width; (2) the Cleft Palate–Craniofacial Journal (formerly the Cleft Palate Journal) from 1964 to November 2008 was hand searched; and (3) the reference lists of all relevant publications were reviewed to identify any publications not already identified using the above two search strategies. Two independent reviewers assessed all the articles with respect to the inclusion and exclusion criteria. Interexaminer conflicts were resolved by discussion of each article to reach a consensus.

Selection Criteria

Studies published as full-length articles reporting quantitative data on the relationship of cleft severity and maxillary growth were selected. No restrictions were placed on sample size, but case reports, abstracts, and letters were not considered. Only articles written in English were included.

Data Collection and Analysis

Data were extracted on the following items: year of publication, sample size, material and age, methods and measurements, and outcome. In addition, to document the methodological soundness of each article, a quality evaluation modified by the methods described by Jadad et al. (1996) and Antczak et al. (1986) was performed with respect to pre-established characteristics. The following nine characteristics were used: sample size, selection description, cleft completeness, withdrawals declared, valid methods, confounding factors considered, method error analysis, blinding in measurements, and adequate statistics. The quality of each article was categorized as low (three or fewer characteristics fulfilled), medium (four to seven characteristics fulfilled), or high (eight or nine characteristics fulfilled). The data were extracted from each article by two independent evaluators and without blinding. Interexaminer conflicts were resolved by discussion of each article to reach a consensus.

Results

A total of four studies (Suzuki et al., 1993; Peltomaki et al., 2001; Honda et al., 2002; Nakamura et al., 2005) met the above criteria and were included in the following review. All studies were retrospective and longitudinal. Three studies were conducted by the same group (Suzuki et al., 1993; Honda et al., 2002; Nakamura et al., 2005). Summarized data of the four studies are listed in Table 1. The variables used to describe the cleft severity in the four studies are provided in Table 2. The variables used to describe the maxillary growth in the four studies and the significant variables from statistical analysis are presented in Table 3.

Table 1

Details of Included Studies Regarding Cleft Severity and Maxillary Growth in Patients With Unilateral Cleft Lip and Palate^*

					Surgery			Assessment
Study No./Author(s)	Design	No. of Patients	Cleft Type/Subtype	Population Studied	Sequence (Mean Age at Surgery in Months)	Hard Palate Repair Technique	No. of Surgeon (s)	Age	Method
1. Suzuki et al. (1993)	Longitudinal	39 (22M)	CUCLP	Japan	L (3–7) å P (21–28)	Modified pushback	3	21–28 mo, 3.9–4.6 y	• Clinical exam • Dental cast ceph (Lat, PA)
2. Peltomaki et al. (2001)	Longitudinal	24 (?M)	CUCLP	?	L+N+A^† (3–4) P (12–14)	Cutting's technique	1	26 d, 5–6 y	• Dental cast • Ceph (Lat)
3. Honda et al. (2002)	Longitudinal	31 (?M)	CUCLP	Japan	L (4.8) å P (23.3)	Modified pushback	≥4	145 d, 16.5 y	• Dental cast ceph (Lat) • Ceph (Lat)
4. Nakamura et al. (2005)	Longitudinal	20 (?M)	UCLP (16 CUCLP, 4 IUCLP)	Japan	L (4.4) å P (24)	Modified pushback	?	135 d >15y	• Facial cast • Ceph (Lat)

M = male; ? = not available; (I)(C)UCLP = (incomplete)(complete) unilateral cleft lip and palate; L = lip; P = palate; N = nose; A = alveolus; d = days; m = months; y = years; Ceph = cephalometric radiograph; Lat = lateral; PA = posteroanterior.

†

All had presurgical nasoalveolar molding.

Table 2

Variables Used in Included Studies Relating Cleft Severity (Study Numbers as per Table 1)^*

	Cleft Severity
	Cleft Size		Palate Size				Face Deformity
Study No.	Anterior	Posterior	Total	Greater	Lesser	Difference	Nose	Upper Lip
1		h–h'
2	G-L		Arch C	Arch L
3				S	S	S
				V	V
4	CL width						AB depth difference	L difference
							AB height difference	S
							NB width difference	S difference
							CB deviation

h–h' = posterior cleft width; h = intersection of interhamular line and margin of cleft (‘denotes cleft side); G-L = anterior cleft width; G = anterior endpoint of the alveolar crest of the greater segment; L = anterior endpoint of the alveolar crest of the lesser segment; C = circumference; L = length; S = surface; V = volume; CL = cleft lip; AB = alar base; NB = nose base; CB = columella base.

Table 3

Relationship of Cleft Severity and Maxillary Growth in Included Studies (Study Numbers as per Table 1)^*

	1	2		3		4
	Cleft Size	Cleft Size	Palate Size	Palate Size		Face Deformity
Maxilla	Posterior	Anterior	Total	Greater	Lesser	Nose	Upper Lip
Length	×	-a	+a	+b	×	-b	×
Height
Anterior	×			×	×	×	+c
Posterior	×			+d	+d	×	×
Width	+e
Protrusion	×	-f	+f	+g	-h	×	×

X = no significant correlation; + = significant positive correlation; - = significant negative correlation; a = Co-A, ANS-PNS; b = A depth, A'-Ptm'; c = _{ANS-y; d} = PNS-y; e = J-J'; f = SNA, Ba-N-A; g = SNA in adolescence; h = SNA at cheiloplasty.

A quality analysis of the four studies is presented in Table 4. None of the four studies were methodologically ideal. All but one (Peltomaki et al., 2001) had several methodological deficiencies. Three studies used sufficient sample size (i.e., n > 20; Suzuki et al., 1993; Peltomaki et al., 2001; Honda et al., 2002). The selection description was inadequate in all studies. The common deficiency included sampling strategy and gender distribution (Table 1). Withdrawals (dropouts) were not declared in any of the studies. In all studies, the methods used to detect and analyze the cleft severity or maxillary growth were valid and well known. However, method error analysis was done only in two of the studies (Peltomaki et al., 2001; Honda et al., 2002), and none provided information as to whether the measurements were taken blindly. The used statistical method was judged as inadequate in two studies (Honda et al., 2002; Nakamura et al., 2005). The errors were different. Honda et al. (2002) analyzed repeated measurements independently at two time points. Nakamura et al. (2005) used a parametric method for data that were nonnormal. None of the studies considered possible confounders. Two of the studies (Suzuki et al., 1993; Peltomaki et al., 2001) did not continue long enough (i.e., at least in preadolescence) to provide convincing results (Table 1).

Table 4

Quality Analysis of the Included Studies (Study Numbers as per Table 1)

Study No.	Sample Size	Selection Description	Cleft Completeness	Withdrawals Declared	Valid Method	Confounding Factors Considered	Method Error Analysis	Blinding in Measurement	Adequate Statistics Provided	Judged Quality Standard
1	Sufficient	Inadequate^*	Yes	No	Yes	No^†	No	No	Yes	Medium
2	Sufficient	Inadequate^‡	Yes	No	Yes	No^§	Yes	No	Yes	Medium
3	Sufficient	Inadequate^∥	Yes	No	Yes	No^∥	Yes	No	No	Medium
4	Insufficient	Inadequate^‡	No	No	Yes	No^#	No	No	No	Low

Lack of sampling strategy and description of excluding syndromic patients.

†

Possible confounders included gender, number of surgeons, and age at clinical examination.

‡

Lack of patient population and gender distribution.

Possible confounders included gender and age at cast.

∥

Lack of sampling strategy, gender distribution, and description of excluding syndromic patients.

∥

Possible confounders included gender, number of surgeons, and age at cast.

Possible confounders included gender, cleft completeness, number of surgeons, age at cast, and age at cephalometry.

Maxillary Length

All studies that met the selection criteria examined the cleft severity and the maxillary length (Suzuki et al., 1993; Peltomaki et al., 2001; Honda et al., 2002; Nakamura et al., 2005). The results from the relevant studies are conflicting. Peltomaki et al. (2001) concluded that cleft size is related to the maxillary length, whereas Suzuki et al. (1993) opposed this view. Two studies (Peltomaki et al., 2001; Honda et al., 2002) concluded that palate size is related to the maxillary length. On the other hand, Nakamura et al. (2005) reported that nose deformity is related to the maxillary length (Table 3).

Maxillary Height

Of the four studies that met the selection criteria, three (Suzuki et al., 1993; Honda et al., 2002; Nakamura et al., 2005) examined the cleft severity and the maxillary height. Suzuki et al. (1993) concluded that cleft size is unrelated to the anterior height. On the other hand, Honda et al. (2002) concluded that palate size is related to the posterior height. Nakamura et al. (2005) showed that upper lip size is related to the anterior height (Table 3).

Maxillary Width

Only one study (Suzuki et al., 1993) that met the selection criteria examined the cleft severity and the maxillary width and reported that cleft size is related to the maxillary width (Table 3).

Maxillary Protrusion

All studies that met the selection criteria examined the cleft severity and the maxillary protrusion (Suzuki et al., 1993; Peltomaki et al., 2001; Honda et al., 2002; Nakamura et al., 2005). Two studies agreed that palate size is related to the maxillary protrusion (Peltomaki et al., 2001; Honda et al., 2002). On the other hand, Peltomaki et al. (2001) concluded that cleft size is related to the maxillary protrusion, whereas Suzuki et al. (1993) opposed this view. Nakamura et al. (2005) reported that face deformity is unrelated to the maxillary protrusion (Table 3).

Discussion

This systematic review was undertaken to answer the following questions: Is cleft severity related to later growth of the maxilla? Is a severe cleft related to unfavorable maxillary forward growth? To answer these questions, an exhaustive literature search was performed in an attempt to find all studies involving cleft severity and facial growth. Overall, only four studies were reviewed. The small number of studies may be related to the bias in location and selection of the studies for inclusion in the review. Studies with significant results are more likely to get published than studies without significant results (i.e., publication bias); among published studies, those with significant results are more likely to get published in English and more likely to be cited (i.e., English-language bias and citation bias, respectively). According to the selected studies, we found cleft severity to be related to later growth of the maxilla. The relationship of a severe cleft and unfavorable maxillary forward growth has not been established. However, the finding about the cleft severity and the later growth of the maxilla is far from robust because of the poor quality of most selected studies.

The article review provided inconclusive evidence about the relationship of a severe cleft and unfavorable maxillary forward growth in patients with UCLP. The reasons for discordant results from the studies include the heterogeneity of the studies, as shown by the variety of the ages or methods used in evaluating cleft severity and maxillary growth (Table 1); extended variables used in describing cleft severity (Table 2) and maxillary growth (Table 3); and methodological deficiencies (Table 4). These are described in more detail as follows.

The cleft severity is usually evaluated from its appearance at birth. Peltomaki et al. (2001) evaluated the cleft severity at birth. On the other hand, Honda et al. (2002) and Nakamura et al. (2005) evaluated the cleft severity when lip repair was undertaken; Suzuki et al. (1993) evaluated at the time of palate repair (Table 1). In a recent study, Berkowitz et al. (2005) demonstrated that a small cleft at the time of palate repair leads to favorable maxillary forward growth, suggesting cleft size at the time of palate repair is a predictor of growth outcome.

Many methods have been used to evaluate the cleft severity, ranging from manual measurement of mouth (Suzuki et al., 1993) and dental casts (Peltomaki et al., 2001) to computer-aided measurement of dental (Honda et al., 2002) and facial (Nakamura et al., 2005) casts. The cleft severity was described in terms of cleft size, palate size, or face deformity (Table 2). Suzuki et al. (1993) measured the cleft size (i.e., posterior cleft width) intraorally. Peltomaki et al. (2001), using dental casts, measured the cleft size (i.e., anterior cleft width) and palate size (i.e., arch circumference, arch length). More recently, the introduction of the surface laser scanning of dental (Honda et al., 2002) or facial (Nakamura et al., 2005) casts has made it possible to capture three-dimensional (3D) models of casts and make accurate 3D measurements. Honda et al. (2002) described the method as accurate and reliable when they measured the palate size (i.e., palate area, palate volume). Nakamura et al. (2005) measured the face deformity on the nose (alar base, nasal base, columellar base) and upper lip (length, width, surface) in distances, angles, and areas.

Results from Peltomaki et al. (1993), Honda et al. (2002), and Nakamura et al. (2005) all showed that the cleft severity is related to the maxillary growth. However, the cleft severity indicator and its effect differ (Tables 2 and 3). Also, the age at cephalometric assessment for maxillary growth varies (Table 1). Peltomaki et al. (2001) found both the cleft size (i.e., anterior cleft width) and palate size (i.e., arch circumference) have an influence on maxillary forward growth in early childhood. The smaller the anterior cleft width and the larger the arch circumference, the longer and more protruded the maxilla. The negative correlation between anterior cleft width and maxillary forward growth might be explained by the fact that all the patients had undergone gingivoperiosteoplasty before lip repair. Honda et al. (2002) reported that the palate size (i.e., greater segment area, greater segment volume) has an effect on the maxillary forward and downward growth in adolescence. The larger the greater segment, the longer and more protruded the maxilla. The larger the greater segment, the longer the posterior maxillary height. On the other hand, Nakamura et al. (2005) revealed that both the nose and upper lip deformities have an influence on the maxillary forward and downward growth in adolescence, respectively. A small difference of alar base height is related to a long maxilla. In addition, a large upper lip is related to a long anterior maxillary height.

Although we aimed to perform a meta-analysis of the included studies, this appeared to be impossible because of heterogeneity of the studies, as discussed above. Also, because three of the four studies were conducted by the same group (Suzuki et al., 1993; Honda et al., 2002; Nakamura et al., 2005), independency of the three samples is highly unlikely.

To our knowledge, this is the first systematic review reporting on the relationship of cleft severity and maxillary growth in patients with UCLP. After assessing the selected studies, several conclusions can be drawn.

Because of contradictory results and the poor quality of most selected studies, the scientific evidence was too weak to answer the question whether a severe cleft is related to unfavorable maxillary forward growth.

Further well-designed controlled studies as well as long-term studies are needed, and researchers have to consider combined assessment of cleft size and palate size. Further studies should also focus on the cleft severity at birth and at the time of palate repair.

Researchers should also consider confounding variables (e.g., cleft subtype, age, gender, and surgeon), use correct statistical methods and reliable outcome variables (e.g., SNA and S-N-ANS for maxillary forward growth), and perform method error analysis and blinding in measurements.

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