Introduction
Cleft lip and palate (CLP) is the most common congenital malformation caused due to variation in development of facial structure during gestation resulting in discrepancy in form and function with varied severity.1 The maxillary component in patients with CLP is segmented by the cleft involving palate and alveolus. The extraoral clinical features in unilateral cleft defect are characterised by wide base of the nostril and clefting of the upper lip on the affected side. The nasolabial deformities are a major challenge for the initial surgical procedures and affect the final aesthetic outcome.
Presurgical Infant Orthopaedics (PSIO) is defined as “use of forces to reposition tissues secondarily displaced due to a cleft deformity”. 2 The aim of PSIO is to decrease the width of the cleft gap, to achieve a favourable alignment in the cleft segments within the initial few months of infancy prior to cheiloplasty, and to allow surgical repair with minimal tension.3, 4
PSIO has been used in treatment of patients with CLP for centuries, however it was Hoffmann in the year 1689, who demonstrated that the cleft can be narrowed with the usage of facial binding and thereby prevent postsurgical dehiscence.5, 6 Adhesive tape binding usage 7 and strapping the premaxilla 8, 9 gradually evolved. The modern school of PSIO using a series of plate system was introduced by McNeil. 10, 11, 12 followed by Latham’s appliance, Hotz plate.13, 14 Matsuo’s (1988-91) series of research on neonatal molding on nasal cartilage and nostril with help of silicone tubes was the gateway to invent newer modern methods. 15, 16, 17 The paradigm shift in PSIO treatment in patients with CLP was with introduction of Nasoalveolar molding (NAM) by Grayson and Cutting in 1993, a novel technique in which presurgical molding of the alveolus, lip and nose is done in infants born with CLP.18
The ultimate goal of PSIO is to reduce the cleft width so to ease soft tissues under tension, thus helping in surgical repair of lip for better aesthetic results. The other added benefits are improvement and ease in feeding, increased volume of fluid intake, subsequently weight gain, improvement in functioning of tongue, reduced risk of aspiration, nasal symmetry, improvement in airway, and reduction in severity of dental & skeletal deviations.19, 20, 21
The aim of present systematic review is to thoroughly evaluate clinical evidence necessary to critically appraise and systematically summarize the long term outcome of PSIO in patients with CLP.
Materials and Methods
Protocol development and eligibility criteria
A comprehensive protocol was considered and accordingly Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines were followed. 22 Study protocol was registered on International Prospective Register of Systematic Reviews (CRD42020195879). The following focused question formulated in the Patient, Intervention, Comparison and Outcome format was developed: “Does PSIO have long term positive outcome on patients with CLP?”
Information sources and search strategy
The evidences were searched using internet sources and manual search for suitable papers, cross references satisfying eligibility criteria of study. The electronic database of National Library of Medicine (MEDLINE PubMed), Cochrane, and manual search using institutional library resources was carried out. The keywords or the Medical subject headings (MeSH) that were used to recognize pertinent articles and full electronic search strategy for each database are illustrated in Table 1 respectively.
Study Records and Selection Criteria
Inclusion criteria and exclusion criteria
PICOS format was utilized for formulating inclusion and exclusion criteria (Table 2).
Inclusion criteria
Full text English articles published till Feb 2021
Studies from January 2011 to 2021 were included (previous systematic review published in 2011 included articles from 1963 to 2010.23
Randomised Control Trails (RCT) that reported data on treatment outcome of PSIO with controls without PSIO.
Prospective and retrospective controlled clinical trials (CCTs) that reported data on treatment outcome of PSIO with controls without PSIO.
Studies with follow-up period of minimum of 5 years
Study Selection and Data Collection Process
The selection of articles at each stage is presented in Figure 1 in which the flow diagram is adapted from PRISMA -2009. 22 A positive exclusion method was used, whereby publications that did not meet one or more of inclusion criteria were excluded. In step 1, only titles and abstracts were collected from the records from Jan 2011 till Jul 2020. Step 2 involved removal of duplicated articles. In step 3, the copies of full articles were reviewed from those selected in step 1 and the ones which did not qualify inclusion criteria were excluded. Both steps of the review process were done twice by author AB.15 articles which satisfied the selection criteria were included in the present study 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37. The distribution of the journals in which these articles are published is tabulated in Table 4.
Exclusion of studies
Twenty four studies were excluded from the review because they did not satisfy the selection criteria [A1-A24].(Table 5 and reference as per Appendix A).
Data extraction and quality analysis
The data in the form year of publication, study design, materials (study sample, control sample), type of presurgical appliance, methods of measurement, outcome and authors’ conclusions were summarised. (Table 5 ) A quality evaluation of the methodological soundness of each article was performed for the studies according to ‘‘The Oxford Centre for Evidence-Based Medicine Levels of Evidence’’ criteria. 38 The following characteristics were used to evaluate accordance with the standards: study design, sample selection description, blinding in measurements, and provision of adequate statistics (Table 6 ).
Results
The search strategy resulted in 111 articles, of which 15 were qualified for the final analysis. The studies included in this review, characteristics of participants, type of interventions, outcome measures are summarized in Table 5.
The meta-analysis
Although a total of 15 studies were included in this review, meta-analysis was possible to be performed for only 05 of them due to heterogeneity of material, method and type of PSIO used. Figure 2 shows the Meta-analysis for mean difference of parameters (Study group versus control group). In the meta-analysis, a statistical test of heterogeneity was performed. 40, 41 The test of heterogeneity seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in the published findings is compatible with chance alone (homogeneity). From the results obtained through meta analysis, it is clear that there is a significant heterogeneity reported in the literature in terms of mean difference between study group and control group being included in this review study (Q Statistic : 569.52523, P-value<0.001, I² 99.3% (Table 8). A forest plot (blobbogram) of estimated results using 5 selected studies addressing the same question, along with the overall results was formulated (also called pooled effect). Forest plot, that includes the effect-sample size with 95% CI found in the studies included in the meta-analysis. The funnel plot along with Begg-Mazumdar’s statistically non-significant Kendall tau value shows clear evidence of non-existence of publication bias (P-value>0.05).
Table 1
Search strategy database
Table 2
PICOS criteria for selection of studies
Table 3
Distributionof the journals in which the 15 selected articles were published
Table 4
Referencesof excluded studies with rationale for exclusion
Table 5
ClinicalSummaries of the selected articles
|
Author and year of publication |
Study design |
Study sample |
Appliance |
Outcome |
Conclusion |
|
Astani et al23 |
Cross-sectional retrospective study |
40 patients with CLP 26 with NAM, 14 without NAM |
NAM |
Pharyngeal Airway |
There is an effective enlargement in nasopharyngeal airway size in patients with CLP after NAM, more apparent in BCLP than UCLP individuals after NAM |
|
Bonanthaya et al24 |
Cross-sectional retrospective study |
121 patients with CLP 59 with NAM 62 without NAM |
NAM |
Nasolabial aesthetics |
Nasolabial aesthetics at post cheiloplasty were significantly better in patients who had undergone NAM in infancy. |
|
Broder et al25 |
Nonrandomized, prospective, multicenter Study |
110 infants with CLP 62 with NAM 48 without NAM |
NAM |
Nasolabial aesthetics |
Infants who underwent NAM were perceived by caregivers to have better post surgical outcomes than those who underwent lip repair without NAM |
|
Hosseini et al 26 |
A systematic review and meta-analysis of randomized controlled trials |
118 patients with unilateral complete CL/P and 16 with cleft of the soft and at least two thirds of the hard palate. |
PSIO |
Feeding, general body growth, facial esthetics, speech and language evaluation, caregiver-reported outcomes, economic evaluation, as well as, adverse effects and problems |
No significant effect of investigated PSIO protocol on outcome |
|
Jodeh et al 27 |
Meta analysis |
1241 patients with CLP from 15 studies |
PSIO |
Development of oronasal fistula |
Multiple benefits in relation to facial and nasal form with PSIO in patients with CLP . |
|
Liang et al 28 |
Prospective, randomized clinical trial |
84 patients with CLP 42 with NAM 42 without NAM |
NAM |
Nasolabial aesthetics |
NAM is beneficial when used as an early-stage adjunctive therapy during nasal deformity correction before primary cheiloplasty; however it is lacks long-term nostril symmetry maintained after primary cheiloplasty. |
|
Liu et al 29 |
Systematic review of Cohort studies and RCT |
756 patients with CLP |
NAM |
Surgical, esthetic, functional, and socioeconomic effects |
NAM appliance therapy can offer positive outcome on patients with UCLP when performed before primary repair surgeries |
|
Maillard et al 30 |
Systematic review of RCTs, prospective , retrospective studies |
1893 patients with CLP |
PSIO |
Surgical, esthetic, functional, and socioeconomic effects and the three-dimensional technology |
NAM appliance therapy can offer positive outcome on patients with UCLP before the primary repair surgeries. Three-dimensional technology results in a more efficient and predictable NAM treatment. |
|
Noverraz et al 31 |
Prospective two-arm randomized controlled trial (DUTCHCLEFT) |
43 patients with CLP wearing Passive plate, 46 patients with CLP not wearing plate |
Passive maxillary plate |
Maxillary transverse arch relation |
Passive maxillary plate does not show significant changes in transverse dental arch relationships in patients with CLP. |
|
Papadopoulos et al 32 |
Systematic review and meta-analysis of randomized controlled trials |
200 patients with CLP |
PSIO |
Feeding, general body growth, facial esthetics, speech and language evaluation, caregiver-reported outcomes, economic evaluation, as well as, adverse effects and problems |
Evidence cannot support the short or long-term effectiveness of PSIO treatment in patients with CLP |
|
Saad et al 33 |
Prospective randomized controlled clinical trial |
40 infants with nonsyndromic UCLP 20 NAM-treated group 20 non–NAM treated group |
NAM |
Maxillary arch dimensions |
NAM in patients with CLP minimizies cleft severity, and realigns the maxillary arch segments with no worsening in transverse and vertical arch growth. . |
|
Shetty et al 34 |
Nonrandomized, prospective, Study |
150 patients with CLP |
NAM |
Nasolabial dimensions |
Improvement in Nasolabial dimensions was seen with the NAM protocol. . |
|
Shetty et al 35 |
RCT |
60 patients with CLP |
NAM |
Maxillary arch dimensions |
PNAM aids in improving the maxillary arch symmetry as well as stability, and helps in preventing arch collapse in the long term. |
|
Thierens et al 36 |
Systematic review |
587 patients with CLP |
Labial adhesion and lip strapping |
Alveolar and palatal cleft width |
There is an effective reduction in alveolar and palatal cleft width with usage of labial adhesion with or without infant orthopedics. However the long term effect on nasolabial esthetics remains uncertain |
|
Van der Heijden et al |
Systematic review |
212 patients with CLP |
NAM |
Nasal symmetry |
Positive effect is appreciated in respect to nasal symmetry with the usage of NAM. |
Table 6
ROBI Sassessment of systematic reviews
|
Study |
Study eligibility criteria |
Data collection and study appraisal |
Synthesis and findings |
Risk of bias in the review |
|---|---|---|---|---|
|
Hosseini et al 26 |
High |
High |
High |
Low |
|
Papadopoulos et al32 |
High |
High |
Low |
Low |
|
Maillard et al 30 |
High |
High |
Low |
Low |
|
Liu et al 29 |
Low |
Low |
Low |
Low |
|
Thierens et al 36 |
High |
Low |
Low |
Low |
|
Van der Heijden et al 37 |
Low |
High |
Low |
Low |
Table 7
|
Article
|
Study Design
|
Selection Description
|
Blinding in Measurements
|
Adequate Statistic Provided
|
Oxford Centre Level of Evidence-2010
|
|
Astani et al23 |
Retrospective study |
Adequate |
Mentioned |
Yes |
2b |
|
Bonanthaya et al 24 |
Retrospective study |
Adequate |
Mentioned |
Yes |
2b |
|
Broder et al 25 |
Prospective study |
Adequate |
Mentioned |
Yes |
2b |
|
Hosseini et al 26 |
Systematic review and meta-analysis |
Adequate |
- |
Yes |
1a |
|
Jodeh et al 27 |
Meta analysis |
Adequate |
Mentioned |
Yes |
1a |
|
Liang et al 28 |
RCT |
Adequate |
Mentioned |
Yes |
1b |
|
Liu et al 29 |
Systematic review |
Adequate |
- |
Yes |
1a |
|
Maillard et al 30 |
Systematic review |
Adequate |
- |
Yes |
1a |
|
Noverraz et al 31 |
RCT |
Adequate |
Mentioned |
Yes |
1b |
|
Papadopoulos et al 32 |
Systematic review and meta-analysis |
Adequate |
- |
Yes |
1a |
|
Saad et al 33 |
RCT |
Adequate |
Mentioned |
Yes |
1b |
|
Shetty et al 34 |
Prospective, Study |
Adequate |
Mentioned |
Yes |
2b |
|
Shetty et al 35 |
RCT |
Adequate |
Mentioned |
Yes |
1b |
|
Thierens et al 36 |
Systematic review |
Adequate |
- |
Yes |
1a |
|
Van der Heijden et al 37 |
Systematic review |
Adequate |
- |
Yes |
1a |
Table 8
Meta-analysis of Effect sizes of Mean difference ofpost-op parameters (PSIO Group vs Control Group).
Discussion
PSIO concept for treating the patients with CLP has been integrated as the standards of care in many treatment protocols teams around the world. The definitive treatment for patients with CLP is followed after the development of face. 24 The PSIO treatment being one of the first approaches in treatment protocol (NAM being the commonest method), it is imperative to study the long term outcome of the procedure keeping in mind the variation of growth in the face of the individual. Thus, the focused question of this systematic review was about the long-term outcome of PSIO in patients with CLP, which require a relevant, evidence-based evaluation in various outcome parameters like feeding, general body growth, facial and nasolabial aesthetics, airway, maxillary arch dimension, speech as well as adverse effects and problems. The studies included in the present review were with the long term effect of PSIO on various parameters. The longest follow up period among the studies selected was an RCT with follow up of 12 years. 31 However the selection of a large sample of untreated control group is not easy and comparing the true effect of PSIO is very difficult.
Feeding and general body growth
PSIO in the form of active or passive appliances seems to have no evident positive effects on feeding function and successive effect on growth and development outcomes in the form of height and weight. There seems to be no considerable differences between patients with CLP who received PSIO treatment in comparison with patients with CLP who did not receive such treatment. 26, 32
Facial and nasolabial aesthetics
The long term effect of PSIO seems to have no lasting effect on facial aesthetics when assessed by full-face and nasolabial photographs. 32 Treatment of patients with CLP with PSIO performed before primary repair in infancy enhances nasolabial aesthetics by improving its symmetry due to active nasal molding of the lower lateral nasal cartilage. 24, 26, 29, 30, 34 Better results in facial appearance and aesthetics were reported after primary cleft lip and nasal repair in the infants who underwent PSIO compared with the control group. 25 The repositioning and approximation of cleft segments benefited surgeons in marking and dissection during the operation, with a less invasive surgery leading to reduction in recovery time 28, 37
Airway
The patients with CLP who underwent PSIO treatment during infancy were assessed for the long term outcome in relation to upper airway parameters. Nasopharyngeal, oropharyngeal, and total airway volumes of all the patients with CLP were calculated with the help of 3D CBCT. There were statistically significant differences in nasopharyngeal volume in PSIO group compared to control group. The oropharyngeal and total pharyngeal airway were not statistically significant. The amount of nasopharyngeal, oropharyngeal, and total pharyngeal airway size in patients with BCLP of PSIO group was significantly more than that of patients with BCLP of control group. Thus it was concluded that PSIO can effectively enlarge the nasopharyngeal airway size in patient with CLP. 21
Maxillary arch dimension
The patients with CLP who underwent PSIO treatment with passive maxillary plate during infancy showed that the long term transverse dental arch relationships at 9 and 12 years of age had no statistically significant difference between children with UCLP treated with or without PSIO 32. It was concluded that the orthodontic requirement to perform PSIO in infants with UCLP with an aim for maxillary transverse expansion is not necessary. However PSIO improves arch symmetry and stability by reducing the cleft width, minimizing cleft severity, realigning maxillary segments without the deterioration of the transverse and vertical arch growth. Thus, it may prevent arch collapse in the long term. 33, 35, 36
Speech
The patients with CLP who underwent PSIO treatment had positive effects on speech and further associated language development. In comparison to patients who were not treated with PSIO, treated infants had a considerable normal phonetics development, improved production of alveolar contoids & oral plosives, superior intelligibility, and longer utterances in their speech. The improvement changes in speech were temporary as the effects faded away in long term. The long term assessment of speech at the age of 6 years did not show any significant effects when compared to no treatment. 26, 32
Adverse effects /unfavourable/ pitfalls and problems
The patients with CLP undergoing PSIO treatment generally do not present significant adverse effects when compared to each other or to no treatment. However minor reports of tissue and skin ulceration due to application of pressure by intra oral appliances, irritated mucosa and skin over the cheek region, dislodgement of intra oral plates, excessive alar expansion leading to mega nostril are also documented. Sometimes due to the poor and unmonitored molding process, wherein the greater segment of cleft moves more rapidly, without the change in position of the lesser segment, resulting the lesser segment to get locked out behind the greater segment known as locked-out segments. 26
Strengths and limitations
The strengths of the present review include systematic approach using standard protocol and guidelines of search strategy, risk of bias, and summarizing the evaluation of various PSIO outcome parameters like feeding, general body growth, facial and nasolabial aesthetics, airway, maxillary arch dimension, speech as well as adverse effects & problems. Limitations of the review included the heterogeneity of the level of study in various parameters for outcomes of PSIO.
Recommendations
The definitive long-term outcomes of PSIO protocols are of utmost importance in patients with CLP; however it can only be recognized after completion of facial development. The level of evidence varies in long term outcomes of various parameters of PSIO. Further research with equal selection of level of evidence can justify the different parameters for long term outcome of PSIO.
Conclusions
The zeal for PSIO is increasing among orthodontists working on patients with CLP, so as to look for better surgical outcomes with minimal requirement of surgery.
The PSIO in patients with CLP shows significant positive changes in nasolabial aesthetics and pharyngeal airway in long term.
These results should be considered with caution as the heterogeneity of included studies cannot be denied.
Hence, more controlled and well conducted studies should be performed, focussing on the individual parameters for long term outcome of PSIO.
Article DOI
