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Abstract

Background:To date, there is little guidance regarding current adjuvant therapies for primary surgical repair of cleft lip. There are studies on the effect of botulinum toxin type A, revision fat grafting, silicone gel and sheeting, intense pulsed light, and carbon dioxide lasers to ameliorate contracture and hypertrophic scar formation, but a comprehensive review of these options is lacking. The aim of this scoping review is to examine adjuvant techniques and therapies that modulate scar outcomes for primary cleft lip repair outcomes in the perioperative period. Methods: PROSPERO, PubMed/MEDLINE, SCOPUS, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrial.gov were searched for studies that evaluated adjuvant therapies for primary cleft lip repair. Results: The initial search resulted in 688 studies, with 48 studies including relevant key terms in the title and abstract screening. After the full-text screening, 11 studies were included in the final scoping review. These included 3 studies about use of botulinum toxin injection, 2 studies about fat grafting, 2 studies about nasal stents, and 4 studies about various topical treatments. In the Jadad quality index evaluation and MINORS assessment of the methodological quality of the included papers, there was a strong level of agreement among the 2 raters respectively (weighted κ = 1, κ = 0.817, both P-value < .0001). Conclusion: From this scoping review, adjuvant therapies such as utilizing botulinum toxin and immediate fat grafting intraoperatively and nasal stents and topical treatments including antibiotic ointment, lidocaine, hydrogen peroxide, and silicone gels postoperatively are worthwhile to consider as a combination of adjuvant treatments to prevent adverse scar formation in patients undergoing primary cleft lip repair. The most robust evidence lies with botulinum toxin use.

Keywords

cleft lip repair cleft lip scar scar prevention botox fat grafting

Introduction

Cleft lip is among the most common congenital anomalies affecting the head and neck, with an incidence of 0.1% in the general population.¹ Delivery of effective care requires a multidisciplinary approach to meet the needs of this complex patient population. From a treatment standpoint, emphasis has always been placed on the surgical approach for defect and structural correction. While various surgical techniques for cleft lip repair have been analyzed to provide tangible guidelines and recommendations for physicians, the surgical approach is only one aspect of the treatment plan^2,3 Intraoperative and post-operatively adjuvant therapy for primary cleft lip repair has the potential to optimize surgical recovery, mitigate adverse scar formation, and improve the psychosocial well-being of patients.

A variety of protocols exist to discuss management after surgical repair including feeding protocols, pain management, and prophylactic antibiotics.^2,4-6 However, guidance regarding adjuvant therapies for primary surgical repair is limited. Independent studies have examined the use of botulinum toxin type A, revision fat grafting, silicone gel and sheeting, intense pulsed light, and carbon dioxide (CO₂) lasers to ameliorate contracture and hypertrophic scar formation.^7-12 Other studies have attempted to use fat grafting, fillers, or autologous tissue transfers to achieve the desired contour and improve volume deficiencies.^13,14 To date, a comprehensive review of such adjuvant treatment options to inform the cleft provider has yet to be published. Therefore, the aim of this scoping review is to examine different adjuvant techniques and therapies that modulate scar healing to improve the esthetic outcome for primary cleft lip repair outcomes in the perioperative period.

Methods

This scoping review was conducted in accordance with the JBI SUMARI methodology for scoping reviews.¹⁵ All reviews and meta-analyses were excluded. Study quality was assessed using the Jadad et al and Methodological Index for Nonrandomized Studies instruments.^16,17 All included studies were Level of Evidence I-IV.¹⁸

Search Strategy

The search strategy, including all identified keywords and index terms, was adapted for each database. PROSPERO, PubMed/MEDLINE, SCOPUS, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrial.gov were searched. Only studies published in English were included. There was no restriction on the publication date range. Experimental, quasi-experimental, and analytical observational studies including prospective and retrospective cohort studies, case-control studies, and analytical cross-sectional studies were included.

Key terms included a combination of Medical Subject Headings (MeSH) terminology including cleft lip or harelip, cleft lip therapy, injections, Botox, botulinum toxin, platelet rich plasma, silicone, hydrocolloid bandage, scar massage, nasal stents, nasoalveolar molding or NAM therapy, presurgical orthopedics or Latham device or Dynacleft, hydrogels, perioperative care, newborn or infant or child or pediatric, and English language.¹⁹ For additional details including the full search strategy, please refer to the Supplemental Materials.

Patients with syndromic and non-syndromic cleft lip, including unilateral and bilateral, who underwent primary cleft lip repair were included. Patients undergoing secondary cleft lip repair or revision were excluded. Interventions had to be performed either intraoperatively or immediately postoperatively. There were no minimum or maximum follow-up duration and no standardized measurement of the outcomes. Studies that examined operative techniques, revision techniques, flap designs, antibiotics, nursing care, feeding techniques, hospital care, nasoalveolar molding, and other forms of presurgical orthopedics were excluded.

Study Selection

Upon search completion, all identified citations were collated and uploaded into JBI SUMARI.¹⁵ Two independent reviewers (M.L., J.P. || medical students) screened studies by title and abstract for assessment against the inclusion criteria for the review. After screening for relevant abstracts, the full text of selected citations was assessed in detail against the inclusion criteria by 2 independent reviewers. Reasons for exclusion of papers at the full-text stage were recorded. Any disagreements that arose between the reviewers at each stage of the selection process were resolved with an additional reviewer (M.J.P. || craniofacial surgeon). The results of the search and the study inclusion process were reported in full in the final review and presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram (Figure 1).²⁰ Data was extracted by 2 independent reviewers using a standardized data extraction tool.¹⁵ Extracted data included patient demographics, study methodology, study location, context, interventions, and cleft lip surgical outcomes.

Figure 1.

Results from literature search in the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram.

Results

Study Inclusion

The review resulted in 688 studies, with 48 studies including relevant key terms in the title and abstract screening. After the full-text screening, 11 studies were included in the final scoping review (Figure 1). Reasons for exclusion included ineligible participant characteristics and ineligible intervention. Included studies were then grouped into 4 groups by associated intervention methods: botulinum toxin studies, fat grafting, nasal stents, and dressings and topical treatments.

Using the Jadad quality index evaluation of the included papers, there was perfect agreement among the 2 raters (weighted κ = 1, P-value < .0001). Using the MINORS assessment of methodological quality on the included papers, there was a strong level of agreement among the 2 raters (κ = 0.817, P-value < .0001).

Characteristics of Included Studies

Characteristics of included studies are tabulated in the Table 1. Four randomized controlled trials, one quasi-experimental multi-center study, 2 case series, and 4 case control studies met inclusion criteria. The included studies took place in the United States of America (3), Taiwan (3), Belgium, Germany, Latvia, Lithuania, Estonia, Mexico, India, and Nigeria. Adjuvant therapies evaluated included botulinum toxin (3), dressings and topicals (3), nasal stent (2), fat grafting (2), care package, silicone gel. There were no studies found that used platelet rich plasma or scar massage alone. The studies were grouped by associated intervention methods: Botulinum Toxin, Fat Grafting, Nasal Stents, and Dressing and Topical Treatments.

Table 1.

Study Characteristics and Data From Included Studies.

Authors	Published Year	Country	Type of Study	Level of Evidence	Intervention Category	Participant characteristics	Intervention and Groups	Measured Outcomes	Description of Main Results	Follow up Assessment
Chang CS, Wallace CG, Hsiao YC, Chang CJ, Chen PK.	2014	Taiwan	Randomized Controlled Trial	I	Botox	59 patients (average age of 3.13 mo) with unilateral cleft lip	Experimental (botulinum toxin): 30 patients (19 male:11 female) Control (saline): 29 patients (19 male:10 female)	Width of scars (Vancouver Scar Scale) and Visual Analog Scale	Measurements of scar widths at two defined points in the experimental group revealed significantly better visual analog scale scores (P < .001). Vancouver scar scale assessments were similar between groups (P > .05).	6 mo
Sonane J, Sharma RK, John JR, Sharma R.	2022	India	Randomized Controlled Trial	I	Botox	28 patients (aged 6 mo and older) with unilateral cleft lip	Experimental: Primary lip repair with botulinum toxin injections Control: Primary lip repair with saline injections	Vancouver Scar Scale (VSS) and Visual Analog Scale (VAS)	Botox group had a statistically significantly better VAS score and lesser scar width compared to the control group but no statistically difference between VSS scores. No improvement was seen in the scar pigmentation.	6 mo
Navarro-Barquín DF, Lozada-Hernández EE, Tejeda-Hernández M, DeLeon-Jasso GA, Morales-Rescalvo FE, Flores-González E, et al.	2019	Mexico	Randomized Controlled Trial	I	Botox	22 patients (3 mo to 3 y old) with unilateral or bilateral cleft lip with or without palate	Experimental: 11 patients with cleft lip and palate who received 8 IU Botox injection prior to primary cleft lip repair Control: 11 patients who received saline prior to cleft lip repair	Width of scar (Vancouver scar scale)	Clinical and statistical difference between the experimental and control group in the width of the scar in 3 mo and 6 mo and Vancouver Scar Scale. The difference between groups from 3-months post-operation was a scar width (mean ± SD) of 1.70 ± 0.67 mm and 4 ± 1.65 mm, (p=0.003). After 3-months, the experimental group showed a mean of 2.0 ± 1.05 and 3.78 ± 1.20 (P = .004) for the control group.	3 and 6 mo
Gbolahan OO, Ogunmuyiwa SA, Osinaike BB.	2015	Nigeria	Randomized Controlled Trial	II	Dressings and Topicals	40 patients with cleft lip -/+ palate	Experimental: 20 patients who received primary cleft lip repair did not have any dressing cover Control: 20 patients who received primary cleft lip repair with traditional wound dressing cover	Wound outcome complications and cosmetic appearance of cleft lip repair (patient satisfaction, scar diameter)	1/20 of no-dressing group had a wound infection with gram-positive staphylococcus aureus culture. No infections occurred in the dressing group. Minor wound dehiscence occurred 3/20 in the dressing group and 4/20 in the no-dressing group. No statistically significant difference between groups for scar diameter and patient satisfaction. The diameter of scar with dressing was 3.29 mm and 3.62 mm without dressing, at the fifth to eighth week review.	5-8 wk
Nagy K, Mommaerts MY.	2011	Belgium	Case series (prospective cohort)	IV	Dressings and Topicals	Patients from 1991 to 2009 who underwent primary unilateral or bilateral cleft lip repair at the Bruges Cleft and Craniofacial Centre (199 unilateral and 103 bilateral cleft lip patients).	Patients who had wound ointment applied (Tetracycline HCl, water, Sorbitan monooleate, paraffin, white Vaseline, Lidocaine HCl)	Post-operative course, including infection, readmission, dehiscence, secondary operations.	Over 19 y, 2.6% showed postoperative infection and/or dehiscence. 1% required readmission for reoperation. 1.6% was treated with oral antibiotics from a post-operative inflammatory reaction.	Follow up period not specified.
Chang CS, Wallace CG, Hsiao YC, Huang JJ, Chen ZC, Chang CJ, et al.	2018	Taiwan	Case Control (mixed prospective and retrospective)	III	Dressings and Topicals	57 patients who underwent primary cleft lip repair	Experimental: 29 age-matched patients (3.17 mo average) received self-dry silicone Control: 28 patients (average age of 3.36 mo) received standard postoperative silicone sheeting	Vancouver scar scale, visual analog scale, scar width assessments	The Vancouver scar scale, visual analog scale and photographically assessed scar width assessments were the same in both groups at 6 mo after surgery. However, silicone gel has the safety advantage that it cannot be swallowed by young patients.	6 mo
Strong AL, Nauta AC, Kuang AA.	2015	United States	Case series (retrospective)	IV	Dressings and Topicals	146 patients between age 0 and 4 who underwent primary cleft lip repair and cleft rhinoplasty from 2006 to 2011 patients.	Patients who had immediate postoperative application of half-strength hydrogen peroxide and bacitracin, and scar massage at wound site. Nearly 85% of patients had cosmetically pleasing scars, including no hypertrophy or discoloration less than 1 y after surgery. Additionally, 2% of patients were revised upon after 1 y.	Postoperative outcomes, including absence of incisional dehiscence, hypertrophic scar formation, or discoloration at the surgical site.	124 patients had favorable cosmetic outcome and 3 patients developed suboptimal outcomes necessitating secondary surgical revision.	<1 y
Zellner EG, Pfaff MJ, Steinbacher DM.	2015	United States	Case Control (retrospective)	III	Fat grafting	35 children (44 sides) between 2 and 20 mo (average, 4.9 mo; SD, 3.8 mo) who underwent unilateral or bilateral cleft lip repair with or without autologous fat grafting. Twenty-six clefts were unilateral and nine were bilateral, and 19 were incomplete and 17 were complete cleft lips.	Experimental: 19 patients who underwent primary cleft lip repair with autologous fat grafting Control: 16 patients who underwent primary cleft lip repair without autologous fat grafting	Postoperative photographic assessment of cleft-related stigmata of face, upper face, mid face, nose by blind reviewers.	Patients scored at >6 mo showed that areas were improved in the fat-grafted cohort, and upper lip improvement reached statistical significance. The experimental group showed a ((P < .01) in the full face, (P < .01) in the upper lip, and (P < .01) in the midface. There was not an improvement in the nose, (P = .06), in which only the upper lip maintained its significance after the 6-month review at (P < .02).	>6 mo
Balkin DM, Samra S, Steinbacher DM.	2014	United States	Case Control (retrospective)	III	Fat grafting	30 children (37 sides), 1.5 to 6.4 mo old (mean 3.5 mo) who underwent cleft lip repair with or without simultaneous fat grafting, aged 1.5 to 6.4 mo. 7 bilateral, 13 left, 10 right cleft lip.	Experimental: 20 infants who underwent cleft lip repair with primary fat grafting Control: 10 infants who underwent cleft lip repair without primary fat grafting	Complications, post-operative photographic assessment for left stigmata (overall, upper lip, nose, midface)	No complications in operative and post-operative period. Post-operative photographic assessment in fat grafted patients showed improved overall appearance of face (P = .0013), (P = .0001) in the upper lip, (P = .0003 in the nose, and (P = .0013) in the midface. Each ordinal score was statistically significant compared fat grafted repairs to those without fat grafting (p < 0.05).	6 and 12 mo
Lenz JH, Akota I, Zaleckas L, Soots M, Bagante I, Rogovska I, et al.	2021	Baltic Cleft Network: Germany, Latvia, Lithuania, Estonia	Quasi-Experimental Study (multi-center clinical trial)	III	Nasal Stent	All non-syndromic patients with complete unilateral cleft lip, alveolus, and palate born in 2000 onward.	Center 1: 42 patients who had nasoalveolar molding and Hotz plate starting within 2 wk Center 2: 19 patients who had Hotz plate starting within 2 wk and nasal stents at 3 mo post-operatively. Also had primary anterior rhinoplasty. Center 3: 15 patients who did not have pre-surgical orthodontics or nasal stents	Evaluation of photographs at 10 y old of the nose, white lips, scar, and vermillion.	The nasal scores did not differ much between center 1 and center 2, although noses of center 3 declined (P = .0078). The scars of center 3 were rated better than those from the other centers (P = .0036). In contrast, no statistical differences have been found regarding white lips and vermilia. The results following NAM were not better than results following primary anterior rhinoplasty plus postoperative nasal stents.	10 y
Yeow VK, Chen PK, Chen YR, Noordhoff SM.	1999	Taiwan	Case Control (retrospective)	III	Nasal Stent	60 patients with complete unilateral cleft lip and palate patients (3-6 mo old when surgery was performed). Photos of patients were taken when between 5 and 8 y old.	Experimental: 30 patients with cleft lip repair and post-operative silicone nasal stents for at least 6 mo Control: 30 patients with cleft lip repair and no nasal stents	Postoperative photographic analysis (residual deformity scale and appearance scale 1-5)	Nostril symmetry, cartilage slump, alar base, and columella tilt were statistically significantly different between the two groups, with nasal stents making a meaningful difference in outcomes.	Between 5 and 8 y

Measured primary and secondary outcomes from adjuvant therapies varied by study, including the Vancouver Scar Scale (VSS), Visual Analog Scale (VAS), complications and patient safety, patient compliance, and general cosmetic appearance or photographic assessment for cleft stigmata.

Botulinum Toxin

Three randomized controlled studies used botulinum toxin as adjuvant therapy and reported outcomes using the VAS, VSS, and scar-width scales.^21-23 In all 3 studies, the VAS score and scar width measurements were significantly improved postoperatively after 6 months, and some showing improvement in 3 months. Two of the 3 randomized controlled trials did not show significant improvement in the VSS scale after 6 months.^21,22

Fat Grafting

Two perioperative, primary cleft lip repair studies, which were categorized into a prospective study and retrospective analysis respectively, both showed significant improvement in overall patient satisfaction with fat grafting.^24,25 Weeks after the operation, independent reviewers were asked to assess the full face, upper lip, nose, and midface on a five-point scale (ranging from “invisible stigmata” to “very visible” stigmata) for cleft-related facial stigmata postoperative photos on a five-point scale. In both studies, results showed significant improvements in the full face, upper lip, midface.^24,25 In the retrospective study, there was lasting significant improvement in all regions after 6 months for unilateral cleft lip and 12 months for bilateral cleft lip while the prospective study only showed improvement in the lip region after 6 months.^24,25

Nasal Stents

Two studies examined nasal stents, with one study retrospectively comparing the application of postoperative nasal stents alone and the other examining the use of nasal stents in combination with other inventions compared to other presurgical and postoperative methods in a multicenter trial.^26,27 With at least 6 months of nasal stent use, 5-to-8 years postoperative photographs showed that nostril symmetry, alar cartilage slump, alar base level, columella tilt, and overall esthetic appearance were significantly improved compared to the group that did not use it.²⁶ In the multicenter clinical trial, 3 centers had different interventions: center 1 consisted of 42 patients that had presurgical nasoalveolar molding (NAM) and presurgical Hotz plates, center 2 consisted of 19 patients who had a presurgical Hotz plate and postoperative nasal stents, and center 3 consisted of 15 patients without presurgical orthodontics or postoperative nasal stents.²⁷ Postoperative photographs were evaluated using a visual rating scale of the nose, lip skin, lip scar, and vermillion. Nose evaluations were comparable from NAM (center 1) and nasal stents (center 2).²⁷ However, lip scars from operations without NAM or nasal stents (center 3) were rated better compared to operations with NAM and nasal stents.²⁷ All centers experienced no statistical difference regarding lip skin and vermillion.²⁷

Dressings and Topical Treatments

In a randomized controlled trial in Nigeria, dressings did not have an impact on scar formation as there was no statistically significant difference between the 2 groups on postoperative complications and scar diameter.²⁸ Topical treatments for primary cleft repair include ointments, silicone sheets, and hydrogen peroxide application. One center described their specific postoperative regimen and examined their incidence of postoperative complications and scar appearance after primary cleft lip repair. This regimen included intravenous amoxicillin for 2 days postoperatively, and oral amoxicillin during feeding, Logan bar with adhesive tape, immediate post-operative local anesthetic solution, saline cleaning, elbow restraints, and custom ointment, including tetracycline, sorbitan monooleate, paraffin, white Vaseline, and lidocaine, which was applied twice daily at the hospital and for 2 weeks after discharge. The results showed that 2.6% of patients had a postoperative infection and/or dehiscence, 1% had a secondary operation, and 1.6% had a post-operative inflammatory reaction that was treated successfully with oral antibiotics over 19 years.²⁹ In another study comparing standard silicone sheet and self-drying silicone gel on the incision site immediately postoperatively, after 6 months, VSS and VAS scores were not different between the 2 groups.¹² In a retrospective study examining the application of hydrogen peroxide, where primary cleft lip incision sites were treated with half-strength hydrogen peroxide, bacitracin, and a scar massage in all patients, about 85% of patients had cosmetically favorable scars, which includes no hypertrophy or discoloration at the surgical site, at less than 1 year postoperatively.³⁰

Discussion

As demonstrated in this review, adjuvant surgical techniques can improve cosmesis, aid healing, and prevent fibrosis after primary cleft lip repair. Many of the current adjuvant therapies are derived from adult scar revision and modulation. However, the pediatric population presents unique challenges such that stability of the wound and adherence to treatment cannot be guaranteed. The results of our scoping review have illustrated many of the options available to surgeons for primary cleft lip repair, including botulinum toxin, fat grafting, use of nasal stents, silicone gel, hydrogen peroxide, antibiotic ointment.

Botulinum Toxin

Preventing adverse scar formation in the lip area is challenging due to essential role of the orbicularis oris in feeding and speaking. Since tensile and mechanical forces are key players in the formation and widening of scars, the injection of botulinum toxin in the early phases of healing can help to immobilize the local area until collagen matures. Botulinum toxin blocks the presynaptic release of acetylcholine, temporarily paralyzing the muscle to reduce tensile forces on the repair.³¹ Additionally, botulinum toxin directly inhibits the release of inflammatory molecules, such as serotonin, that can mitigate scar hypertrophy.³² For over 25 years, botulinum toxin has been used safely and successfully in the pediatric population, mainly for cerebral palsy and other spastic muscle conditions. While botulinum toxin has been shown to successfully improve facial scars during revision surgery of hypertrophic and depressed scars, it has not been widely adopted for use in primary cleft lip repair.^33,34 In our review, the measured outcome played a large role in the success of the botulinum toxin intervention, with all studies showing scar improvement when measured by scar width and VAS scale, and not all showing improvement with VSS scale, which was also confirmed in a recent systematic review of botulinum toxin treatment for scar prevention in primary cleft lip repair.³⁵ Given these results, botulinum toxin injection in combination with other scar modulating treatments is a promising adjuvant treatment for primary cleft lip repair. Botulinum toxin injections have also been successfully used for cleft lip revisions in adults immediately after wound closure, resulting in significant improvement of lip scarring.¹¹ However, a limitation for widespread use is insurance coverage and the cost of each treatment.

Fat Grafting

Fat grafting has been found to improve skin quality and scar appearance while enhancing contour and structure, and incorporating this procedure into primary cleft lip repair is believed to help mitigate potential postoperative complications.³⁶ Mechanically, fat grafting helps to mitigate physical depressions and balance the contours of the nasolabial complex. Previous research has shown that pediatric and adult patients who had additional lip irregularity after primary cleft lip repair and underwent a revision operation with fat grafting had significantly improved satisfaction, cosmetic outcome, and decreased cleft stigmata.^13,37-41 Some studies have even examined how fat grafting can improve functional and speech outcomes for patients with velopharyngeal insufficiency.^42,43 The studies in our review have shown that fat grafting does have a lasting impact on both scar appearance and contour. However, fat retention and contour retention over long periods vary, so additional fat grafting procedures may have to be performed. In addition to its structural and functional impact, fat grafting can also have regenerative benefits, as adipose tissue contain adipose-derived stem cells (ADSC) can support wound healing and regeneration.^44-51 Therefore, fat grafting techniques have the potential to assist in the correction of asymmetry by soft tissue augmentation and provide a milieu for tissue regeneration, making it an attractive option in primary cleft lip repair.⁵² However, higher level of evidence studies are needed to further define its role in primary cleft lip repair.

Nasal Stents

Nasal stents or splints are often used immediately postoperatively after primary cleft lip repair for at least 6 months, as they help to prevent the lower lateral cartilage and alar of the nostrils from collapsing during the wound healing process. A nasal stent or splint is comprised of 2 hollow tubes made from silicone, rubber, or other pliable materials, with a connection between the 2 tubes that will lie along the columnar bridge of the nose.²⁶ The literature mainly consists of studies examining the effect of nasal stents in combination with preoperative regimens such as presurgical orthopedic devices, NAM, the Latham appliance, and Dyna cleft, so evidence is limited on the effect of nasal stents alone. While nasal splints have been used in other fields such as trauma or burns to keep the nasal airway open, their use in cleft lip care is limited to the last 2 decades. However, the limited studies have been impactful, impacting postoperative care guidelines for all cleft lip and palate patients. Nasal stents or splints are also inexpensive and easily understood by caretakers, likely facilitating compliance.

Dressings and Topicals

Postoperative wound dressings are utilized as a simple, cost-effective physical barrier to enhance wound healing, reduce pain, protect the wound from foreign material and bacteria, and reduce healing time.⁵³ The variety in effectiveness and benefits of dressings is centralized on maintaining the correct amount of moisture in the wound bed. Effective mediums and materials such as topical pain medication, silicone gel sheets, and antibiotic ointments can also be beneficial tools in cleft lip post-operative care to impact healing and scar formation. Semi-permeable dressings serve as a barrier for infection while allowing for moisture regulation and evaporation. Hydrogels, which provide a moist environment for wounds to heal, are shown to have high patient satisfaction when utilized in primary cleft lip repair.⁵³ Silicone products have also been described to be an effective therapeutic strategy to prevent pathologic scarring. A review of randomized controlled trials of silicone products compared to onion extract gel (Contratubex^®; Merz Therapeutics; Frankfort, Germany) illustrated that silicone products, including both silicone sheets and gel, were superior in the treatment of hypertrophic scars.⁵⁴ However, in more recent systematic reviews studying the efficacy of silicone gel sheeting for prevention of abnormal scarring, there has been limited evidence demonstrating its effectiveness.^55,56 Although the exact mechanism of action has not been defined, proposed theories include providing bacterial and barrier protection, modulation of inflammation, and hydration to the wound bed.⁵⁷ The benefits of silicone gel include its comparable efficacy profile, inability to be ingested (unlike silicone sheets), and its easy application to irregular surfaces.^29,55,58,59 As another proposed topical treatment, hydrogen peroxide is a useful adjunct in postoperative care; however, its efficacy and potential toxicities are heavily debated in other wound use cases.⁶⁰ However, the study included in our review found significantly reduced rates of wound dehiscence, hypertrophic scar formation, or discoloration at the surgical site.³⁰ This benefit, in combination with the low cost and accessibility of hydrogen peroxide, can make it an effective option for wound care management.

Limitations

From this scoping review, it can be concluded that there are many effective adjuvant treatments that can be implemented for scar modulation in primary cleft lip repair. However, these studies are varied in measured outcomes, typically combined with other treatments, and limited in strong evidence for each of the reviewed interventions. Many of these studies have therapies without a control group, are retrospective, have small sample sizes, or combine multiple treatments, such as scar massage, silicone gel, and ointments, some that are unreported, so it is difficult to definitively conclude a specific treatment’s efficacy alone. Our review only found a few studies per treatment category, with most of the current literature on adjuvant treatments for scar modulation studying scar modulation as a whole, but not primary cleft lip scars. Outside of our review, there is a lack of data summarizing adjuvant treatments cleft providers can use perioperatively for primary cleft lip repair.

Conclusion

Adjuvant therapies to mitigate scar formation can be beneficial tools in a cleft provider’s postoperative care regimen. From this scoping review, using botulinum toxin and immediate fat grafting intraoperatively, utilizing nasal stents and topical treatments such as antibiotic ointment, lidocaine, hydrogen peroxide, and silicone gels immediately post-operatively, and using laser treatment later in the cleft lip patient’s care are worthwhile to consider as a combination of adjuvant treatments to prevent adverse scar formation in patients undergoing primary cleft lip repair. The most robust evidence lies with botulinum toxin use, which is supported by several randomized studies.

Supplemental Material

sj-docx-1-fac-10.1177_27325016231212564 – Supplemental material for A Scoping Review of Adjuvant Perioperative Therapies for Primary Cleft Lip Repair

Supplemental material, sj-docx-1-fac-10.1177_27325016231212564 for A Scoping Review of Adjuvant Perioperative Therapies for Primary Cleft Lip Repair by Melinda Lem, Jason T Pham, Jagmeet Arora, Shivang Trivedi, Omotayo Arowojolu, Ruben Castro, Joseph Mocharnuk, Raj Vyas and Miles J. Pfaff in FACE

Footnotes

Acknowledgements

We would like to thank Linda Suk-Ling Murphy for her assistance in this manuscript.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical Approval

Institutional Review Board approval was not required.

ORCID iD

Miles J. Pfaff

Supplemental Material

Supplemental material for this article is available online.

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Supplementary Material

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A Scoping Review of Adjuvant Perioperative Therapies for Primary Cleft Lip Repair

Abstract

Keywords

Introduction

Methods

Search Strategy

Study Selection

Results

Study Inclusion

Characteristics of Included Studies

Botulinum Toxin

Fat Grafting

Nasal Stents

Dressings and Topical Treatments

Discussion

Botulinum Toxin

Fat Grafting

Nasal Stents

Dressings and Topicals

Other Post-Operative Therapies

Limitations

Conclusion

Supplemental Material

sj-docx-1-fac-10.1177_27325016231212564 – Supplemental material for A Scoping Review of Adjuvant Perioperative Therapies for Primary Cleft Lip Repair

Footnotes

Acknowledgements

Declaration of Conflicting Interests

Funding

Ethical Approval

ORCID iD

Supplemental Material

References

Supplementary Material