Effects of various surgical protocols on maxillofacial growth in patients with unilateral cleft lip and palate: a systematic review

Eligibility criteria

This systematic review focused on UCLP patients and their treatment, more precisely the timing of surgical protocols and their effect on maxillofacial growth. For selection of the articles, the following inclusion criteria were applied: non-syndromic UCLP patient population; study population had to be over 6 years old; timing of each surgical procedure had to be known; no orthodontic procedures or orthognathic surgery was performed in the study population after surgical repair and before assessment; a control or comparison group had to be present, the outcome of the article had to be on maxillofacial growth; and evaluation of growth had to be at least based on a cephalogram. From the literature, it was clear that a great variety of landmarks were used in the different studies. The outcome parameters for this review were based on the maxillary position given by the sella-nasion-A-point angle (SNA), the mandibular position given by the sella-nasion-B-point angle (SNB) and the intermaxillary relationship [A-point-nasion-B-point angle (ANB)]. Articles had to provide measurements for at least SNA to be included in this review. Articles were excluded in which other forms of cleft lip and/or palate (cleft lip without cleft palate, cleft palate without cleft lip, bilateral cleft lip and palate) were analyzed. Furthermore, the following studies were excluded: case reports, literature reviews, systematic reviews and meta-analysis. Studies included in this review had to be written in English or Dutch and published after 2005. The goal of this systematic review was to compare various surgical protocols and to conclude which surgical protocol provides the most benefits regarding maxillofacial growth, functionality and aesthetics in UCLP patients of 6 years and older. Factors that would be assessed included: age of assessment, use of presurgical orthopedics, surgical timing, surgical approach (one-stage surgery, one-stage palatoplasty and two-stage palatoplasty), and ethnicity.

Information sources

A search of PUBMED and Web of Science was conducted in December 2019. The keywords used were “UCLP” and “Maxillofacial growth” or “Facial growth”. As a search limit, the publication date was set to 2005 or later. The results obtained were stored in a single database (EndNote X9; Thomson Reuters, Philadelphia, USA). Additionally, a hand search of references of included articles in this systematic review was performed.

Study selection

After removal of duplicates, all articles were screened on title and abstract. This was performed independently by two authors to augment reliability. Any disparity in selected articles was discussed until a consensus was reached. Full-text articles were analyzed regarding our aforementioned inclusion and exclusion criteria. The articles used in the systematic reviews and literature review found through PubMed and Google Scholar were hand searched. The same protocol and eligibility criteria were applied as described above.

Quality assessment and level of evidence

The included articles were reviewed for good quality based on a checklist adopted from Liao et al.^[7]. This checklist was adjusted for our review on the basis of the theory of Greenhalgh^[8] and can be found in the left column of Table 1^[6,9-18]. Studies were considered to be of adequate size if their study population exceeded 100 people; this number was based on the quality assessment applied in the systematic review of Liao et al.^[7]. Using the Oxford Centre for Evidence-Based Medicine 2011 v2.1 the qualified articles were assessed for their level of evidence by two independent reviewers. The levels could be downgraded on the basis of study quality, imprecision, indirectness, or inconsistency between studies, or because the effect size was very small. Disagreements were discussed until the two reviewers gave their consent.

Data extraction

From the final selection of articles, the following information was retrieved: author(s), publication year, study design, population studied, identification of the study groups, number of patients per group, mean age at time of assessment of facial growth, presurgical orthopedics (yes/no), lip closure technique and timing, soft palate closure technique and timing, hard palate closure technique and timing, alveolar cleft closure technique and timing, and final conclusions. The data were extracted from each article by one author and then checked by the second author before being collected in a database. Disagreements were resolved by discussion of each article to reach a consensus.

Study selection

The process of data collection and selection is shown in Figure 1. A total of 314 records were found among the databases investigated and 79 additional records, published after 2005, were identified through hand search of the articles included in this systematic review or provided by specialists on the subjects. After removal of duplicates (n = 103), 290 articles remained that had their titles and abstracts assessed in accordance with the inclusion and exclusion criteria. From this initial reading, 221 records were eliminated. After reading the full texts of the remaining 69 records, 58 articles were excluded for the following reasons: case reports (n = 3); systematic review and meta-analysis (n = 5); literature review (n = 1); other forms of cleft (cleft lip without cleft palate, cleft palate without cleft lip, bilateral cleft lip and palate) were studied (n = 3); patients were younger than 6 years old and therefore not yet in mixed dentition (n = 10); there was no control population (n = 5); no cephalometric analysis was performed (n = 5); surgical timing of lip and palate repair were not known (n = 6); the study did not examine the skeletal maxillary growth pattern (n = 7); angle SNA was not measured (n = 2); or the patient had undergone orthodontic treatment and/or orthognathic surgery after surgical repair and before assessment (n = 11). Therefore, 11 eligible articles were found for this review.

Figure 1. Flow chart showing the number of records identified and removed at each stage of the review. SNA: sella-nasion-A-point angle

Study characteristics

Most studies included in this review (73%) were published after 2010^[6,12-18][Table 2]. Six studies were conducted in Asia (55%) and 5 were conducted in Europe (45%). The variety of treatment protocols that were administered in the different studies in the articles, as well as whether or not presurgical orthopedics was performed, is shown in Table 2. Sample sizes consisted of 10 subjects^[12] to 128 subjects^[18]. Seven articles included a healthy, noncleft control group in their study^{[10,11,13-17]}. The authors used a variety of surgical techniques. Regarding cheiloplasty, the following techniques were used: (modified) Millard rotation-advancement technique^[9-12,15,16], triangular technique (by Tennison with modifications)^[9,11,13,18] and modified Delaire technique^[12]. Three articles did not specify the technique used for lip repair^[6,14,17]. Concerning closure of the palate several techniques are listed, which can be categorized as follows: (modified) von Langenbeck^[9,12,13], pushback palatoplasty^[10], cranial or caudally pedicled vomer flap^[9,12-14,18], intravelar veloplasty^[11], modified Pigott technique^[12] and two-flap palatoplasty^[14-16]. Khanna et al.^[6] provided no description of the technique used for palate repair.

Three different surgical techniques were described for alveolar cleft closure: gingivoperiosteoplasty^[11,12], primary bone grafting^[14] and secondary bone grafting^{[11,12,16,18]}. Three studies declared that the patients in the samples had not undergone bone grafting surgery^[9,10,17], whereas three studies had no information on whether or not bone grafting surgery had been done^[6,13,15].

The mean age at the time of surgical repair in patients with repaired UCLP varied according to the surgical protocol: lip repair before 15 weeks^[6] until 2 years^[15]; soft palate closure from 4 months^[12] to 5 years^[9]; hard palate closure from 3 months^[12] to 4 years^[9] and alveolar cleft repair from 6 months^[14] to 11 years^[12,16].

In 3 studies, the surgical protocol consisted of the primary one-stage surgery of UCLP: simultaneous repair of cleft lip, palate, and alveolus in a single surgical session^[13,14,18]. Five studies applied one-stage palatoplasty^[6,10,15-17] and 2 studies applied both one-stage and two-stage palatoplasty^[9,11]. Meazzini et al.^[12] compared early anterior palate closure by vomer flap during lip repair at 3 months and a two-stage palatoplasty.

The mean age at assessment of maxillary growth through cephalometric analysis varied from 6 to 20 years. The cephalometric values described for each study are summarized in Table 3 and Table 4, classified according to the study population. Cephalometric values of UCLP patients with operated cleft lip and palate (OCLP) in each study were compared with the following groups: UCLP patients treated according to a different protocol^[11-13,18]; UCLP patients with operated cleft lip and unoperated cleft palate^[9,10,15,17]; and non-treated UCLP patients^[6,16], mean value from all centers that completed the Eurocleft study^[14]. In seven studies^{[10,11,13-17]} noncleft children served as normal controls. Among the abovementioned groups, 10 of the 11 included articles^{[6,9-11,13-18]} reported a P-value less than 0.05 for one or more of the cephalometric values SNA, SNB and ANB, whereas one study^[12] did not report a corresponding P-value. A P-value less than 0.05 was regarded as significant.

Quality assessment and level of evidence

The methodological quality of the 11 articles was evaluated using the aforementioned checklist, which can be seen in Table 1. None of the included articles were of perfect methodological quality, they showed different deficiencies, but overall, they were deemed of good quality. Only 4 studies^[9,10,17,18] were deemed large enough, this showing that there is a need for more research with a substantial study population. All included studies were retrospective (level 3 evidence).

Surgical repair and maxillofacial growth

Six out of 11 included articles evaluated the effect that surgery itself has on maxillofacial growth in children with UCLP^{[6,9,10,15-17]}. Khanna et al.^[6] compared a group of treated UCLP patients with a group of non-treated UCLP patients between the age of 12 and 20 years old. They found different values by comparing the cephalometric measurements of the two groups, and they concluded that surgical intervention does interfere with growth in the facial region due to scar tissue in the lip and palate.

Four articles identified the effects of palate repair on maxillary morphology^[9,10,15,17]. These studies recruited patients with non-syndromic UCLP who had lip repair only (OCL) and patients with non-syndromic UCLP who had lip and palate repairs (OCLP). Palate repair at an early stage in patients with UCLP seems to result, in the long run, in a larger retrusion of the maxilla (SNA) and smaller anteroposterior jaw relation (ANB) than in the OCL group, who demonstrated an almost normal maxillary growth^[9,15,17]. Opposed to this view, Li et al.^[10] reported a smaller SNA angle in both OCL and OCLP groups than the normal control group and concluded that lip repair is primarily responsible for the midfacial hypodevelopment in cleft patients.

However, Zheng et al.^[16] attributes the difference in cephalometric results to the intrinsic effect of UCLP on the maxilla resulting in a developmental deficiency and claims that surgery has minor effects on growth disturbances. They discovered that the tendency in patients with UCLP (with or without surgical repair) toward a less protruded alveolar maxilla (SNA) and a more protruded alveolar mandible (SNB) gave rise to the low anteroposterior jaw relation at the alveolar level (ANB).

Surgical technique and maxillofacial growth

Five of the 11 included articles evaluated the effect of different surgical techniques and protocols on maxillofacial growth in children with UCLP^[11-14,18]. Three of the 11 studies looked into the implementation of a one-stage surgery and compared their results with a healthy control population^[11,13,14]. Considering the age at the time of assessment in these 3 studies, the results concerning sagittal growth were very diversified when comparing the outcomes. The study of Zemann et al.^[11] showed no significant difference regarding the angles SNA, SNB and ANB at the age of 6 years old when comparing patients treated according to various one-stage protocols. Furthermore, the acquired values were equivalent to those in a healthy control group. However, Mueller et al.^[14] concluded that maxillary protrusion (SNA) and anteroposterior jaw relation (ANB) in the one-stage groups differed significantly from those of the noncleft, healthy control group, but the degree of disturbance in growth was similar to mean values of multistage approaches in the Eurocleft study. Kulewicz et al.^[13] conducted comparative research into 3 different techniques of palate repair applied to a one-stage surgical approach and checked this against healthy controls. Cephalometric parameter comparison analysis demonstrated significant differences between the 4 groups regarding maxillary prominence (SNA) and maxillo-mandibular relationship (ANB). This indicates that the technique of hard palate closure has a substantial influence on maxillofacial growth and development.

Meazzini et al.^[12] did a comparison between UCLP patients treated with 3 different protocols to evaluate the long-term results between closure of the hard palate at 18-36 months together with early secondary gingivoalveoloplasty (ESGAP) and alveolar cleft repair at 9-11 years of age. Using a longitudinal cephalometric evaluation, they found that patients who underwent ESGAP had a decreased maxillary prominence (SNA) and showed an inhibition of maxillary growth compared with the 2 secondary bone graft groups, while mandibular prominence (SNB) increased in the 3 groups. Nonetheless, performing alveolar bone grafting before 8 years of age is suspected to interfere with anterior maxillary growth, and the timing of bone grafting can be essential to maxillofacial growth. Studies suggested that performing the surgery at a later age would prove the most beneficial^[14,18].