Effectiveness of nasoalveolar molding treatment for babies with nonsyndromic complete unilateral cleft lip, alveolus, and palate: A systematic review and meta-analysis

Abstract

Introduction

This systematic review aimed to compare the effectiveness of nasoalveolar molding (NAM) treatment with no NAM group for babies with nonsyndromic unilateral cleft lip, alveolus, and palate.

Methods

All relevant studies from 1946 to February 2024 were identified using several sources, including The Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, LILACS, Scopus, EMBASE, MEDLINE (Ovid), and ePUB ahead of publications and nonindexed citations. The criteria for this review were as follows: (1) studies with a randomized controlled trial (RCT) and controlled clinical trial (CCT) design; (2) the target population included patients with nonsyndromic complete unilateral cleft lip, alveolus, and palate; (3) the intervention group received NAM treatment before lip repair, whereas the comparison group did not; and (4) the primary outcome was nasolabial esthetics measured using Asher McDade index. All articles were screened for the title, abstract, and full text independently and in duplicate by 2 reviewers. The quality assessment of RCT was performed using Cochrane’s risk of bias tool, and the CCT was assessed using the Risk Of Bias In Nonrandomized Studies of Interventions tool.

Results

Out of the 1432 studies retrieved, 2 RCTs and 3 CCTs were included. One RCT was assessed as having a high risk of bias, whereas the other had an unclear risk. All included CCTs were rated as having a high risk of bias. The studies showed a statistically significant reduction in cleft width favoring the NAM group, and 1 study with a high risk of bias reported significantly better long-term intercanine width for NAM. However, none of the included studies examined long-term or short-term nasolabial esthetics or other functional or esthetic outcomes over the long term.

Conclusions

No conclusions can be drawn on the nasolabial esthetics as none of the included studies evaluated this primary outcome in the short or long term. There is low certainty of evidence supporting the short-term effectiveness of NAM for cleft width reduction in patients with complete unilateral cleft lip, alveolus, and palate. Further high-quality studies are needed to evaluate the long-term effectiveness of NAM treatment, enabling clinicians and patients to make informed decisions.

Registration

The protocol for the systematic review was registered with the International Prospective Register of Systematic Reviews from the National Institute for Health Research database (Prospero No. CRD42024503388).

Funding

This work was supported by the DBT/Wellcome Trust India Alliance Grant (No. IA/CPHS/20/1/505255; awarded to Badri Thiruvenkatachari). (Am J Orthod Dentofacial Orthop 2025;■:■-■)

Introduction

Cleft lip and palate (CLP) is one of the most prevalent congenital anomalies, affecting approximately 1 in 700 live births.¹ CLP is associated with various dental and skeletal anomalies that can significantly impact facial esthetics, function, and self-esteem over the long term. Affected children often require multiple surgeries throughout their lives, beginning with primary cheiloplasty in infancy.

Presurgical infant orthopedic (PSIO) procedures were introduced to improve the alignment of soft and bony tissues around the cleft before lip repair. Initially proposed by McNeil,² these techniques have led to the development of several presurgical orthopedic devices over time. These devices include both active models with screws and pins for retention, as well as passive models, some of which use extraoral strapping or nasal stents.^3,4

The nasoalveolar molding (NAM) appliance is a type of PSIO device designed to correct alveolar segments while simultaneously shaping the nose and enhancing nasal symmetry. The appliance has 2 main components: alveolar molding and nasal molding. The objectives of the former include aligning and approximating the alveolar segments as closely as possible to reduce the post-surgical relapse and to make it possible for a gingivoperiosteoplasty. The nasal molding is performed to reduce nasal deformity, improve the projection of the nasal tip, increase the columella length, and correct the septal position.⁴

The NAM appliance is intended for full-time use, with the primary caregiver responsible for its maintenance and the orthodontist conducting weekly adjustments. Despite its potential benefits, the limited long-term evidence supporting this technique has made it a subject of debate, with some practitioners advocating for its use whereas others remain opposed.

Globally, the Eurocleft project reported that 51.7% of cleft teams in Europe do not implement any form of maxillary infant orthopedics.⁵ In the United Kingdom, a centralized care system for patients with cleft has led to the discontinuation of NAM treatment across all centers.^6,7 A 2011 survey of 117 cleft centers in the United States revealed that 37% offered NAM treatment,⁸ but a more recent survey showed a significant increase, with 86% of centers now providing NAM treatment.⁹

Proponents of NAM argue that these appliances enhance nasolabial esthetics, reduce cleft severity, minimize scarring, lower the need for secondary surgeries, and promote palatal growth.^10–14 Conversely, some studies suggest that NAM may adversely affect future facial growth and increase the caregiver’s burden.^4,15 Furthermore, most studies, including systematic reviews, report no significant long-term differences in speech, facial growth, or esthetics among these children.^3,4 Not only are the findings inconsistent, but many of the studies are of low quality and retrospective in nature. In addition, there is a notable lack of high-quality, long-term studies to substantiate these claims. A previous study on systematic reviews in the field of CLP reported that 77% of published reviews had a high risk of bias, with 58% being graded as low quality.¹⁶ This issue is also evident in earlier systematic reviews on NAM, in which studies of poor quality were included, compromising the overall reliability of the results.^17,18

Given the considerable burden of care borne by children with cleft conditions, it is imperative to thoroughly justify every treatment option offered. Therefore, this systematic review aimed to evaluate the existing literature on the short and long-term effectiveness of NAM treatment in patients with nonsyndromic unilateral CLP (UCLP).

Material and Methods

This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Guidelines 2020.¹⁹

Protocol registration

The protocol for the systematic review was registered with the International Prospective Register of Systematic Reviews from the National Institute for Health Research database (No. CRD42024503388).

Eligibility criteria

Study design

Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing NAM treatment before lip repair with a nontreatment control group were included in this systematic review.

Population

Nonsyndromic patients with complete unilateral cleft lip, alveolus, and palate.

Intervention

NAM treatment before lip repair.

Comparison

No NAM treatment before lip repair.

Primary outcome

Nasolabial esthetics measured using the Asher McDade index.

Secondary outcomes

(1) Cleft width before lip surgery measured in millimeters, (2) arch length measured in millimeters, (3) number of revision surgeries, (4) intercanine width, (5) breakages (yes or no), (6) complications (yes or no), and (7) cost-effectiveness.

Information sources, search strategy, and study selection

Several databases such as The Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, Scopus, EMBASE, MEDLINE (Ovid), Web of Science, and ePUB were searched from 1946 to February 29, 2024, for all relevant studies to be included in the systematic review. The studies were included without restrictions on language and date of publication. Google Scholar and PubMed were also searched for completion, including all relevant articles. In addition, the ongoing and unpublished studies were searched using Dissertation data (www.theses.com), Grey literature (www.opengrey.eu), ClinicalTrials.gov (http://www.ClinicalTrials.gov), and ISRCTN registry (http://www.controlled-trials.com). A sample search strategy is shown in Supplementary Table I.

To identify unpublished studies and ongoing trials, the respective first-named authors were contacted. From the identified articles, the reference lists and relevant review articles were also checked for further possible studies to be included.

The potentially relevant articles were screened for the title and abstract independently and in duplicate by 2 reviewers (S.C. and B.T.) after the removal of the duplicates. The reviewers were not blinded to the authors or the results of the research. The full-text articles were examined for eligibility independently by 2 authors (S.C. and B.T.), and disagreements were resolved after discussion.

Data items and collection

Data extraction was performed for the selected articles using a prepiloted data extraction form (Supplementary Table II). The data extraction was completed for all the included studies independently and in duplicate by 2 reviewers (S.C. and B.T.). Discrepancies in the extracted data were resolved through discussions. Details included in the data extraction form were as follows: (1) general information such as extractor details, time, etc.; (2) study information such as title, year, authors, etc.; (3) study eligibility including Population, Intervention, Comparator, and Outcome assessment; (4) risk of bias; (5) characteristics of included studies such as details of the trial, participants, interventions, etc.; and (6) outcomes such as short-term and long-term nasolabial esthetics, cleft width before lip surgery, arch length, breakages, complications, quality of life, and cost-effectiveness.

Risk of bias/quality assessment in individual studies

Cochrane Collaboration’s risk of bias 2, as described in the Cochrane Handbook for Systematic Reviews of Interventions, was used to assess the risk of bias in the included RCTs.²⁰ Risk Of Bias In Nonrandomized Studies of Interventions I tool was used to assess the risk of bias for non-RCTs.²¹ The risk of bias was assessed separately by 2 independent reviewers (S.C. and B.T.). Any potential disagreements were resolved by discussion between the 2 reviewers. The overall risk of bias for each study was summarized as low, unclear, or high.

Summary measures, approach to synthesis, and analysis

The data collection was completed for the eligible studies, and the authors were contacted if further information was needed. The data were grouped and classified into 2 categories: RCTs and CCTs. The RevMan software (version 5.3; The Nordic Cochrane Centre, Cochrane Collaboration; Copenhagen, Denmark) was used to assess the collected data quantitatively.

Mean differences (MD) with 95% confidence intervals (CIs) were calculated for continuous outcomes. In the instance of dichotomous outcomes, risk ratios with 95% CIs were shown. Random effects model was planned as clinical, and statistical heterogeneity was anticipated.

The study protocol and methodology, treatment interventions, timing of data collection, measurement techniques, and measured outcomes were all reviewed to assess and gauge the clinical heterogeneity of the included studies. The Cochrane’s test for heterogeneity and the I2 test were used to assess statistical heterogeneity.

Publication bias

Standard funnel plots and contoured enhanced funnel plots would be drawn to identify publication bias if >10 studies were included in the meta-analysis.

Additional analyses

Sensitivity analyses were planned to address studies at higher risk of bias, publication bias, and other potential sources of heterogeneity. All analyses were undertaken using the RevMan software version 5.4.

Summarizing findings

A summary of findings table was created to record the results of the main outcomes. The Grading of Recommendation, Assessment, Development, and Evaluation instrument was used to assess the quality of the resultant evidence for each outcome.²²

Results

Study selection

The search strategy identified 1432 articles, of which, after removal of duplicates and screening for relevant articles, 20 full-text articles were retrieved for further evaluation. The full-text articles retrieved were assessed for our inclusion criteria, and 15 articles were excluded for specific reasons (Table I). Finally, a total of 5 studies (2 RCTs and 3 CCTs)^23–27 were included for the final analysis. The process of selection of articles is shown in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis flowchart (Fig 1).

Table I. Excluded studies and their reasons for exclusion.

Study No.	Author (y)	Reason for exclusion
1	Alhayyan (2018)	Retrospective
2	Bhutiani (2020)	DSIC-BCLP included
3	Broder (2016)	DSIC-questionnaire study
4	Fuchigami (2017)	DSIC-retrospective
5	Gomez (2012)	DSIC-no control
6	Hui Xi (2014)	DSIC-not prospective
7	Liang (2017)	DSIC-retrospective
8	Mariqueo (2018)	DSIC-retrospective
9	Nuryilmaz (2018)	DSIC-retrospective
10	Quast (2018)	DSIC-grading study
11	Shen (2015)	DSIC-no control
12	Singh (2005)	DSIC-no control

DSIC, does not satisfy inclusion criteria; BCLP, bilateral CLP.

Fig 1.

PRISMA flowchart. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analysis.

Study characteristics

Five studies (2 RCTs^23,26 and 3 CCTs^24,25,27) that included 262 participants evaluated the effectiveness of the NAM appliance before lip surgery (Table II). The 2 RCT studies^23,26 included 68 participants, 42 males and 26 females. Both studies were performed in Egypt. Saad et al²³ used broad inclusion criteria and included Egyptian infants with complete UCLP aged <2 weeks. It was a prospective, 2-arm RCT in which 40 patients were randomly allocated to NAM and non-NAM groups through closed envelope concealment and were analyzed at the end of the study. The maxillary casts were blindly analyzed at 3-time points (initial visit, 3 weeks, and after 6 weeks) to check for the amount and rate of maxillary changes, including the cleft gap in horizontal and transverse dimensions and rotation of the alveolar segments.

Table II. Characteristics of included study.

Study	Participants	Age	Inclusion criteria	Exclusion criteria	Interventions	Outcomes
Saad et al23 Alexandria University, Alexandria, Egypt Prospective, 2-arm RCT	SG: 20 (11 M, 9F) CG: 20 (12 M, 8 F)	SG Initial visit: 13.5 ± 1.6 d After 3 wk: 36.5 ± 2.2 d After 6 wk: 60.9 ± 2.7 d CG Initial visit: 13.3 ± 1.6 d After 3 wk: 36.1 ± 2.3 d After 6 wk: 60.3 ± 2.6 d	Egyptian infants Complete UCLAP Age ≤2 wk Family consented	Non-Egyptian Syndromic CLP Congenital malformations and soft-tissue bands	SG: NAM CG: non-NAM	Changes in cleft width between NAM and non-NAM
Abd El-Ghafour et al26 Cairo University, Cairo, Egypt Prospective, 2-arm RCT	SG: 17 CG: 17 Total: 28 (19 M, 9 F)	SG: 12.58 ± 8.24 CG: 12.74 ± 7.28	Infants UCLAP Aged 1-30 d Medically fit	No information available	SG: D-NAM CG: notreatment	Changes in maxillary arch dimensions between NAM and non-NAM group
Shetty et al25 Nitte University, Mangalore, India Prospective, 3-arm study	60 participants	SG subgroups NAM initiated <1 mo NAM initiated at 1-6 mo NAM initiated 6-12 mo CG subgroups Lip repair at 6 mo Lip repair 6-9 mo Lip repair 9-15 mo	No information available	No information available	SG: NAM CG: non-NAM	Intersegment distance Intercanine width Posterior arch width
Yu et al24 Jiao Tong University, China Prospective CCT Funding: National Natural Science Foundation of China (grant No. 81271 182)	SG: 15 (7 M, 8 F) CG: 15 (7 M, 8 F)	SG: 17.53 d CG: 116.64 d	Nonsyndromic UCLP Complete medical record	No information available	SG: CAD-NAM therapy CG: non-NAM	Maxillary morphologic changes
de Souza et al27 Prospective trial Curitiba, Brazil	SG: 26 (18 M, 8 F) CG: 12 (7 M, 5 F)	No information available	Nonsyndromic UCL/P	No information available	SG: NAM CG: non-NAM	Symmetry of face and maxillary arch Changes in arch perimeter, arch length, and labial frenum angle measured in digital models

SG, study group; M, males; F, females; CG, control group; UCLAP, unilateral cleft lip, alveolus, and palate; D-NAM, digital NAM; CAD, computer-aided design.

Abd El-Ghafour et al²⁶ performed a prospective, balanced, randomized, single-blinded controlled trial with 34 nonsyndromic infants with UCLP (19 males and 9 females) randomly assigned to NAM and non-NAM groups using sequence generation and opaque sealed envelopes. The NAM group received a digitally designed NAM appliance, whereas there was no treatment with the control group. The plaster casts were scanned and analyzed to determine the maxillary arch changes at the start of treatment and after D-NAM but before lip closure to determine the effectiveness of the NAM appliance.

Yu et al²⁴ performed a prospective CCT with 30 patients (14 males and 16 females) grouped into NAM and control groups. Participants in the NAM group received computer-aided design–NAM, whereas the control group did not receive any treatment before lip surgery. The digital models were then analyzed to determine the maxillary alveolar segment changes and compare the results between the computer-aided design–NAM and the nontreatment control group.

Shetty et al²⁵ conducted a CCT in India with 120 patients with UCLP grouped into NAM and nontreatment control groups. Subjects were followed up until 6 years old. The NAM (treatment) group was further subdivided into 3 subgroups (20 patients per group) based on the age at which NAM was initiated: <1 month, 1-6 months, and 6-12 months. Similarly, the non-NAM (control) group was further subdivided into 3 groups based on the age at which undergoing lip surgery was initiated: 6 months, 6-9 months, and 9-15 months. Patients were evaluated at the first visit, before cheiloplasty, and at 6 years old. The intersegment distance, intercanine width, and posterior arch width were analyzed for the groups.

De Souza et al²⁷ evaluated 26 infants with UCLP who were grouped into NAM and nontreatment control groups. The babies were photographed in 2 stages (first month of life and post-NAM but pre-lip surgery) to determine the facial symmetry, and their digital models were analyzed to evaluate the effect of the NAM appliance. The frontal and basilar photographs were taken using a tripod placed from a constant distance using a macro lens digital single-lens reflex camera. The facial symmetry was calculated by measuring the nasal width/intercanthal length ratio, mouth width/interpupillary distance ratio, and columella angle measurement was taken from the standard photographs.

Risk of bias in RCT studies

The methodological quality assessment of 2 RCTs, Abd El-Ghafour et al²⁶ and Saad et al²³ are given in Figures 2 and 3. Saad et al²³ raised concerns because of the lack of information on sequence generation. Abd El-Ghafour et al²⁶ also raised concerns because of the high risk of bias related to uneven intergroup and intragroup gender distribution. In addition, the authors failed to perform an intention-to-treat analysis.

Fig 2.

Risk of bias 2 summary for RCTs. Green, low risk of bias; yellow, unclear risk of bias; red, high risk of bias.

Fig 3.

Risk of bias graph for RCTs. Specific domains are presented as percentages.

Risk of bias for CCTs

The risk of bias for the included CCTs performed using the Risk Of Bias In Nonrandomized Studies of Interventions tool is shown in Figures 4 and 5. All 3 CCTs^24,27 were assessed to be of critical risk. The bias because of the selection of participants was judged as critical in 2 studies as they all used convenience sampling. Shetty et al,²⁵ did not report their sampling technique. Bias in the measurement of outcome was assessed as serious as Yu et al²⁴ and de Souza et al²⁷ did not perform blinding with a high risk that the outcome measure will be influenced by the knowledge of an intervention. In 2 studies, Yu et al²⁴ and Shetty et al²⁵ did not follow an a priori protocol and, thus, introduced selection bias in the reported result.

Fig 4. Risk Of Bias In Nonrandomized Studies of Interventions tool summary for CCTs.

Fig 5.

Risk of bias graph of CCTs. Specific domains are presented as percentages.

Summary of the results

None of the included studies reported on the primary outcome, the short-term or long-term nasolabial esthetics.

Cleft width before lip surgery

All the included studies, except for de Souza et al,²⁷ investigated cleft width before lip surgery and favored the NAM group. Saad et al²³ studied 40 patients and reported a statistically significant change of −13.668 6 0.559 mm in the NAM group and −0.499 6 0.073 mm in the non-NAM group for cleft width at the end of NAM treatment (P <0.001). Abd El-Ghafour et al²⁶ reported a statistically significant change favoring the NAM group with a difference of 6.7 mm (95% CI, 4.28-9.11) between the NAM and non-NAM groups (P <0.001). Shetty et al²⁵ had a sample size of 40 patients and reported a statistically significant difference favoring the NAM group with a difference of −11.45 mm (95% CI, −12.54 to −10.37) between the groups (P <0.001). Yu et al²⁴ had a sample size of 30 subjects and reported a statistically significant difference between the NAM and non-NAM control groups (MD, 4.23; P <0.001).

Arch length before lip surgery

Only 1 of the included studies,²⁷ investigated changes in arch length before lip surgery in NAM and non-NAM groups. The authors defined arch length as the distance from the labial frenum to the center point of the line drawn between the left and right posterior points on the maxillary arch. The results showed a similar arch length in both the NAM and non-NAM groups at the pre-lip surgery time point. However, the pre-NAM baseline arch length was higher in the non-NAM group.

Intercanine width

One study²⁵ evaluated intercanine width at baseline, pre-lip surgery, and 6 years old. The results showed a statistically significantly increased arch length for the NAM group at (3.30 mm; P <0.001) at 6 years old. However, the results were not significant at the post-NAM/pre-lip surgery time point between the NAM and no NAM group (− 0.30 mm; P = 5 0.52).

Other outcomes

Abd El-Ghafour et al²⁶ reported that no significant harms were observed in the treatment group. None of the other outcomes, such as the number of revision surgeries, complications, breakages, quality of life, and cost-effectiveness, were reported in the included studies.

Meta-analysis

Considering the heterogeneity, the CCTs and RCTs were subgrouped for meta-analysis.

Cleft width

The results of the RCTs^23,26 comparing cleft width in NAM and non-NAM groups showed that the cleft width in the NAM group was reduced significantly more than in the non-NAM group (MD, 11.00 [95% CI, 11.88-10.11]; I² 98%) (Fig 6).

Fig 6. Meta-analysis of parallel-group RCTs evaluating cleft width change with treatment.

The results from CCTs^24,25 on cleft width measurement between NAM and non-NAM control group at precheiloplasty showed a statistically significant difference (MD, 10.57 [95% CI 11.52-9.61]; I² 95%), favoring the NAM group (Fig 7).

Fig 7. Meta-analysis of CCTs evaluating cleft width change with treatment.

Intercanine width

The intercanine width in the long term (6 years) was reported in Shetty et al.²⁵ The results showed a statistically significant difference favoring the NAM treatment group (MD, 3.30 [95% CI, 2.58-4.02]) (Fig 8).

Fig 8. Meta-analysis of CCTs evaluating intercanine arch width at 6 years.

Publication bias was not attempted, as there were not enough studies included in the meta-analysis

Summary of findings

The Grading of Recommendation, Assessment, Development, and Evaluation assessment of the quality of the collected evidence for cleft width immediately post-NAM treatment found low-quality evidence in favor of the NAM group compared with the non-NAM group (Table III). The quality of evidence was down-graded because of the high risk of bias in 1 of the 2 included studies and high heterogeneity.

Table III. Summary of findings for the difference in cleft width between pre-NAM and post-NAM (pre-lip surgery) treatment^†.

Outcomes	Anticipated absolute effects‡ (95% CI)		Relative effect (95% CI)	No. of Participants (studies)	Certainty of the evidence (GRADE)$	Comments
	Risk with no NAM control	Risk with NAM treatment
Cleft width difference	Tire inean cleft width difference was 0 mm	MD was 10.64 lower (11.49 lower vs 9.8 lower)	–	68 (2 RCTs)	⊕⊕◯◯ Low¶#	There is some evidence that NAM width reduces cleft width, but the quality of evidence is low

GRADE, Grading of Recommendation, Assessment, Development, and Evaluation.

^†NAM treatment compared with non-NAM control for patients with UCLP. Patient or population: health problem or population. Intervention: NAM treatment. Comparison: non-NAM control; ^‡The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI); ^§GRADE Working Group grades of evidence: (1) high certainty—we are very confident that the true effect lies close to that of the estimate of the effect; (2) moderate certainty—we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different; (3) low certainty—our confidence in the effect estimate is limited: the true effect may be sub-stantially different from the estimate of the effect; and (4) very low certainty—we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect; ^¶Downgraded as 1 of the 2 studies that were at high risk of bias; ^#Downgraded because of high heterogeneity (χ² = 58.33; degrees of freedom = 1; P <0.00001; I² + 98%).

Discussion

The NAM treatment performed before lip surgery significantly reduces the width of the cleft. However, none of the studies included in this review specifically addressed the primary objective of NAM treatment, which is to facilitate nasal molding and enhance nasolabial esthetics. The review does not provide any data on long-term outcomes, as none of the included studies assessed meaningful long-term results.

Quality of studies included

This systematic review included 2 RCTs^23,26 and 3 CCTs.^24,25,27 One RCT²⁶ was considered to have a high risk of bias because of the lack of reporting on sequence generation, significant gender bias, and failure to perform an intention-to-treat analysis. The other RCT²³ was assessed as having a low risk of bias. All included CCTs^24,25,27 were judged to be at high risk of bias, primarily because of improper participant selection and a lack of assessor blinding.

A previous study on systematic reviews in the field of CLP reported that 77% of published reviews had a high risk of bias, with 58% being graded as low quality.¹⁶ This issue is also evident in earlier systematic reviews on NAM, in which studies of poor quality were included, compromising the overall reliability of the results.^17,18 In contrast, this review exclusively includes prospective studies (CCTs and RCTs) that evaluate the effectiveness of NAM.

NAM appliance design and technique

There was a huge variation in the NAM appliance technique and protocol used; of the 5 included studies, 3^24,26,27 used digitally manufactured NAM appliances with nasal stent addition during treatment, whereas the remaining 2 studies^23,25 employed conventional acrylic NAM fabrication using Grayson’s technique. Patient follow-up was conducted weekly in 3^23,24,27 of the 5 studies. Shetty et al²⁵ did not report the frequency of follow-up, whereas Abd El-Ghafour et al²⁶ followed up with patients biweekly. Two studies^23,24 initiated nasal stent use around 3 weeks after starting treatment, 1 study began nasal molding from the outset, another study²⁶ started nasal molding when the cleft width was under 4 mm, and 1 study²⁵ reported beginning nasal correction when the cleft width was between 8 and 10 mm.

Outcomes

Cleft width before lip surgery

Numerous studies have examined the effect of NAM on alveolar cleft width reduction before lip surgery, although most of these are short-term and retrospective. A previous systematic review on NAM highlighted the need for high-quality studies to better inform clinicians about the long-term benefits of NAM treatment.²⁸ This systematic review provides moderate evidence of short-term cleft width reduction; however, no long-term data are available to justify the lasting benefits of the NAM appliance.

Short-term improvements in cleft width do not guarantee that these results will be maintained over time to provide superior esthetic and functional outcomes. Long-term, meaningful data on the functional, dentofacial, and esthetic outcomes of NAM are crucial. It is also important to note that the long-term benefits should outweigh the significantly increased burden placed on caregivers by NAM treatment.

Nasolabial esthetics

Several retrospective studies (refer) have demonstrated that NAM treatment improves nasolabial esthetics in the long term.^13,15,29,30 However, this review included 5 prospective studies, none of which reported on nasolabial esthetics in either the short or long term. This lack of high-quality studies poses a challenge for clinicians when advising patients about the long-term benefits of NAM. This review highlights the urgent need for well-designed prospective studies to evaluate the long-term impact of NAM on nasolabial esthetics.

Arch width

One study²⁵ reported a significant improvement in arch width among NAM patients in the long term. However, these results should be interpreted with caution, as the study was assessed to have a high risk of bias. In contrast, previous studies have reported no significant improvement in intercanine width in the deciduous dentition or arch length.^31,32 The discrepancies among these studies may be attributed to differences in follow-up duration and sample sizes among the studies.

Other secondary outcomes

The other secondary outcomes of this systematic review were the number of revision surgeries, as well as the harms, complications, and breakages associated with the NAM appliance. Although these outcomes are crucial for caregivers in their decision-making process, it is unfortunate that none of the prospective studies reported on them. Although some retrospective studies have claimed a reduction in revision surgeries with NAM,^33,34 these findings have not been substantiated by high-quality studies.

Studies on NAM treatment have reported lip and cheek/skin irritation because of taping and gingival ulceration because of excessive pressure.^35,36 Although Abd El-Ghafour et al²⁶ reported having no significant harm in their population with no further information, none of the studies investigated these outcomes. It has been shown that these side effects are temporary and do not affect the overall outcome or cause long-term effects on patients.³⁶

NAM treatment has a considerable financial burden on caregivers. Although the total direct medical costs associated with the PSIO group are likely higher than the nontreatment group, some studies have reported that the overall cost is less as there is less likely need for further revision surgeries with NAM, and this out-weighs the cost for NAM treatment.^37,38 Unfortunately, none of the studies included in this review reported on this outcome.

Limitations

Because of the difference in study designs and heterogeneity in the outcome measures used, the review was restricted to the number of studies included in the meta-analysis. The other main limitation of this review was the lack of data from the included studies on the primary outcome, nasolabial esthetics. In addition, there was a lack of data on most of the secondary outcomes and a serious lack of data on long-term results from NAM treatment. This shows the urgent need for long-term prospective, high-quality studies on NAM treatment to allow patients to make informed decisions.

Conclusions

1. This review included 5 studies, 4 of which were judged to have a high risk of bias and 1 a low risk of bias.

2. No conclusions can be drawn on the nasolabial esthetics as none of the included studies evaluated this primary outcome in the short or long term.

3. There is low evidence for cleft width reduction with NAM treatment in patients with complete unilateral cleft lip, alveolus, and palate.

4. Further high-quality long-term studies evaluating the effectiveness of NAM appliances are required to inform clinicians and patients globally.

Supplementary Material

Supplementary Data

Supplementary data associated with this article can be found, in the online version, at https://doi.org/10.1016/j.ajodo.2025.01.012