Orofacial clefts are among the most common congenital anomalies worldwide. The global prevalence of cleft palate globally ranges from 1.4 per 10,000 births in Cuba to 25.3 per 10,000 births in Canada.1 This congenital anomaly is correctable through cost-effective surgical interventions.2–4 One study estimated that the repair of cleft lip or palate has the same cost effectiveness of vaccines in low-income and- middle-income countries.5 Cleft-related speech impairment can be profound for the patient, impacting ability to seek gainful employment and ultimately resulting in significant economic impact for households and communities.2,4

The primary goals of the cleft palate repair are to restore functional anatomy, to close the defect, and restore normal speech. Unfortunately, maxillary growth deficiency, palatal fistulae, and inadequate speech are still common complications. Delayed surgery, improper surgical technique, and scarring can produce sub-optimal surgical outcomes, which may result in velopharyngeal insufficiency (VPI).6,7Velopharyngeal insufficiency occurs as a result of a short, immobile soft palate that does not close adequately against the back of the throat, resulting in hypernasal or unintelligible speech.8 The rate of VPI after primary palatoplasty varies between 5% and 30% 9–16 in the literature, which may be attributed to differences in study size, cleft severity, surgical technique, and operative age of the study populations.17

There is still no international consensus on the appropriate timing of cleft palate repair and technique preferences are still debated.18,19 Most literature suggests primary palatoplasty performed after 18 months leads to worse speech and a higher risk of developing VPI.9,20–24 However, some centers still advocate for delayed palatoplasty to limit midface hypoplasia.25Cleft palate can present in varying degrees of severity with or without cleft lip involvement, which makes it difficult for one singular surgical technique to repair all presentations.26 Surgeons are often taught one cleft palate repair technique through mentorship and utilize or modify that one technique for the entirety of their careers. The reluctance to change from a technique one gains proficiency in and undertake a new learning curve discourages change in a surgeon’s approach. Furthermore, technique variations and modifications make comparing surgical outcomes challenging. Surgeon skill itself is another major factor pivotal to postoperative outcomes.27

The timing of cleft palate repair is also difficult to control as it depends on timely presentation of the patient to care, which is often delayed in resource-limited settings.28 Furthermore, the assessment of VPI is not standardized, is subjective, and can vary across languages and settings, confounding the comparison of post-palatoplasty outcomes.29

Understanding appropriate timing and technique in cleft palate repair is imperative in minimizing the negative complications, yet consensus on both is still variable. We hypothesize that there is a lack of high-quality data to standardize recommendations. This systematic review aimed to (1) objectively summarize existing data on potential impact of primary palatoplasty operative age and surgical technique on the risk of developing postoperative VPI, and (2) comment on whether this data can be used to inform best practice and provide recommendations for next steps.

MATERIALS AND METHODS

A systematic review of the literature was conducted after the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines.30 A detailed protocol was registered to PROSPERO (CRD42020193982).31

Information Sources and Search Strategy

A search of PubMed, Embase, and Web of Science was conducted on April 6, 2020 and included twelve search terms (Supplemental Appendix 1, Supplemental Digital Content 1, https://links.lww.com/SCS/F263). The search terms focused on the speech outcomes and the associated surgical interventions of the palate. There was no restriction on publication date. Gray literature was not searched and there was no contact with study authors.

Eligibility Criteria and Study Selection

Eligibility criteria included full-text articles published in English that recorded VPI speech measures after primary palatoplasty. All cleft palate phenotypes were included. The studies were required to include mean age at primary palatoplasty and a measure of either VPI, hypernasality, or a rate of secondary surgical intervention for speech outcomes. Studies were required to have complete speech outcomes correlated with mean age at surgery for a given study population. This review only examined non-syndromic patients to limit confounding factors in the speech outcomes. All studies with an incorrect study focus or missing inclusion criteria were excluded. Case reports, editorials, reviews, and articles without original data were not included in the analysis.

In the first stage, 2 unblinded reviewers (M.X. and D.I.) screened all titles independently to assess relevance to this review’s objective. In the second stage, once the discrepancies between reviewers’ lists were resolved, the 2 reviewers independently screened the remaining study abstracts for inclusion criteria. Discrepancies between reviewers’ lists were solved through discussion. In the final stage, 3 reviewers independently assessed full-text articles (M.X., D.I., J.K.). Disagreements were resolved by discussion and articles that did not meet inclusion criteria were excluded.

Data Extraction

Quantitative data were extracted from the full-text studies including patient demographics, surgical factors, and surgical outcomes in relation to speech. Data extracted from full-text articles by independent reviewers (M.X., D.I., J.K.) included author, year of publication, study design, population size, severity of cleft, palatoplasty operative age (age at soft palate repair if 2-stage), surgical technique (if available), outcomes of the population in relation to speech (VPI, hypernasality, or incidences of secondary surgery for speech), and age at speech assessment. This data were aggregated into a chart created on Microsoft Excel (Microsoft Corporation).

Data Analysis and Synthesis of Results

The data extracted from included articles were too heterogeneous for a meta-analysis. To determine timing as a risk for VPI symptoms after primary palatoplasty, the study population was divided into 4 quartiles based on mean operative age: 0 to 6 months (Q1), >6 to 12 months (Q2), >12 to 24 months (Q3), and over 24 months (Q4). To determine the risk of VPI symptoms after primary palatoplasty by surgical technique, a sub-group analysis was attempted using data from studies that reported common palatoplasty techniques (Supplemental Appendix 1, Supplemental Digital Content 1, https://links.lww.com/SCS/F263). Patients qualified as having VPI symptoms for our analysis through 3 different criteria: those with postoperative VPI, hypernasality, or who underwent a second speech surgery. Patients with normal speech outcomes were considered not to have any evidence of VPI. Data were analyzed using descriptive statistics, χ2 tests, and Kruskal-Wallis tests. Significance was set at P<0.05.

Quality Assessment

Three authors (M.X., D.I., J.K.) assessed 4 factors of study methodology to determine the risk of bias present in the included studies. Judgements were made by one of the authors and checked by one other. The factors included:whether the speech assessor was unblinded to the patient’s surgical or medical history (detection bias), whether there were speech assessment outcomes not reported for the entire study population (attrition bias), whether there were any speech assessments described in the methods that were not reported in the results (reporting bias), and whether a formal speech protocol was used for the speech assessments (other bias). Each bias was rated as either high risk, low risk or unable to be assessed. Selection and performance bias were not assessed as this review covered surgical interventions. The authors believed it to be likely that random sequence generation and allocation concealment would not be present in the included studies, as this would mean withholding the appropriate surgical treatment from some patients. In addition, for performance bias, the authors believed it to be unlikely that the patients and study personnel would be blinded to type of surgical interventions. Therefore, the authors assumed selection and performance bias to be present in the included studies. Publication bias was assumed to be present as the authors only assessed published peer-reviewed studies.

RESULTS Study Selection

The search identified 4740 original articles (Fig. 1). A total of 4636 were excluded and 104 full-text articles were separately reviewed by 3 authors (M.X., D.I., and J.K.). Sixty-nine of the 104 were excluded for failure to report age at primary palatoplasty (n=16), failure to report complete speech outcomes after primary palatoplasty (n=36), or reporting the presence of a syndrome in their populations (n=17). The 35 included studies reported mean age at palatoplasty and VPI-related outcomes.

FIGURE 1:

The PRISMA flowchart of results. PRISMA indicates Preferred Reporting Items for Systematic Reviews and Meta Analyses.

Quality Assessment

Quality assessment of the 35 included studies is shown in Fig. 2. Most studies (n=28, 80%) failed to specify whether speech assessment was blinded. All studies were low risk for reporting bias. Six (17%) did not include speech assessment results for the entire study population. Formal speech assessment protocols were reported in 26 studies (74%).

FIGURE 2:

Results of the risk of bias assessment.

Study Characteristics

Twenty-one included studies (60%) were retrospective and 14 (40%) were prospective. Most were published between 2010 and 2020 (n=27, 77%) (Supplemental Appendix 1, Supplemental Digital Content 1, https://links.lww.com/SCS/F263). The authors of these 35 studies were associated with institutions in 16 countries, with the majority (n=11, 31%) having authors affiliated with institutions in the United States of America (Supplemental Appendix 1, Supplemental Digital Content 1, https://links.lww.com/SCS/F263). The speech outcome used to measure VPI presence was reported as hypernasality in 10 studies (29%), incidence of secondary surgery in 18 studies (51%), and VPI in 7 studies (20%). The majority of studies with speech assessments (n=33, 94%) examined speech outcomes at age 4 years or older (n=29, 88%). This age group is unlikely to develop subsequent VPI and earlier assessment is often unreliable due to age.32

Operative Age

The 35 included studies had 10,795 patients with a weighted mean operative age of 15.7 months (range: 3.1–182.9 mo) (Supplemental Appendix 1, Supplemental Digital Content 1, https://links.lww.com/SCS/F263), and 20% (n=2186) had signs of postoperative VPI. The majority (n=8489, 78.6%) had palatoplasty between age 6 and 12 months (Q2) (Supplemental Table 1, Supplemental Digital Content 2, https://links.lww.com/SCS/F264), and this group had the lowest occurrence of VPI (18.1%, P<0.010). There was a significant difference between Q3 and Q4 (P=0.007), but not between Q4 and Q1 (P=0.409, Supplemental Table 2, Supplemental Digital Content 2, https://links.lww.com/SCS/F264).

Surgical Techniques

Becaues of the heterogeneity in reporting surgical technique across studies an analysis of the VPI risk per procedure was not possible. Nine studies (26%) mentioned only the name of the surgical procedure used, 15 studies (43%) described the surgical procedure in writing or diagrams, and 7 (20%) studies mentioned only the name of the surgical technique and cited a cleft palate repair technique paper. An assessment of surgical techniques was not applicable for 4 retrospective papers that did not collect technique information. Eleven studies (31%) included modifications to techniques.

DISCUSSION

This is the largest review to date examining the risk of developing VPI after primary palatoplasty with respect to operative timing and technique; illustrating that up to 20% of primary cleft palate patients are at risk of postoperative VPI. Previous literature reviews report a 20% to 30% incidence of VPI after primary palatoplasties in non-syndromic patients.29,33 Risk of VPI may also depend on surgical technique and expertise, cleft phenotype, and cleft severity.27 In previous studies, higher rates of VPI have been suggested with more severe clefts (Veau III and IV),32,34 male sex, shorter palate length, large cleft width, and patients with cleft lip and palate compared with isolated cleft palate.35

This analysis found that primary palatoplasty performed between ages 6 and 12 months was associated with a significantly lower risk of VPI; corroborating the long-standing idea that operative age plays a significant role in postoperative speech outcomes.36 However, the authors cannot conclusively advocate for 6 to 12 months as the optimal timeframe owing to a number of reasons: (1) studies included in this analysis lacked statistical power owing to small sample sizes; (2) timing and technique were analyzed in isolation without consideration of other important contributing factors, such as cleft severity, phenotype, and surgeon expertise; (3) measurement of speech outcomes lacked standardized assessments; and (4) nearly 80%t of patients underwent palatoplasty between 6 and 12 months, which could indicate the influence of certain protocols. For example, the Rule of 10s has influenced many surgeons to perform cleft lip repair at 10 weeks of age; to ensure adequate postoperative recovery, the cleft palate in these children was often repaired after 6 months of age.37,38

Our results do not indicate an advantage to early (Q1) or late (Q4) palatoplasty. There is variable consensus on timing of palatoplasty to optimize speech outcomes. Kaplan suggested palatoplasty before 6 months to ensure proper anatomy at the time of speech development at 9 to 12 months.21 Whereas Murthy et al. and Zhao et al. reported slightly superior speech outcomes after late palatoplasty,9,39 other studies report poorer speech outcomes.9,21–24 Many surgeons would recommend performing primary palatoplasty before 12 months of age to correct cleft palate anatomy before speech patterns have developed. It is theorized that younger children have more time to learn and practice speaking with a repaired mechanism, providing an opportunity to ameliorate erroneous speech patterns.36 Intuitively, primary palatoplasty between 0 and 6 months would result in lower rates of VPI, particularly when compared with primary palatoplasty after 2 years of age, contradicting the findings of this analysis.

However, the benefit of palatoplasties earlier than 6 months need to be measured against the risk of midface hypoplasia, which has significant consequences. Furthermore, early repair before 6 months may be difficult due to small anatomy and airways that increase risk for anesthesia complications, airway obstruction, and lack of respiratory reserve.40

Variability in reporting standards among the studies limited our analysis of the timing of cleft palate repair. Among the 35 included studies there was no consistency in (1) the scale/measurement used to evaluate VPI; (2) reporting of VPI outcomes; (3) reporting of operative age; and (4) reporting surgical technique with descriptions or citations. In addition, this review excluded 52 articles for failure to report basic demographics within their studies such as mean operative age and complete postoperative speech outcomes.

Timing of cleft palate repair is variable between centers globally. This variability also exists in the United States, for example, patients in the Midwest tend to undergo palatoplasty later than the West (14.3 versus 13.2 mo) which is even later than in the Northeast (12.9 mo). Eighty-five percent of centers in the United States perform cleft palate repair after 6 months of age. Even in our institution at the Children’s Hospital Los Angeles/ University of Southern California there is variation among surgeons. This variability could be attributed to what surgeons learned during their training or the practical reasons that occur from patient presentation to anesthesia preparation. There are many reasons that contribute to the lack of universal protocols for cleft palate repair. The search for optimal timing is a meticulous investigation for optimal speech results against known iatrogenic effects of palatal surgery demonstrated to have variable degrees of growth disturbances.

An analysis of surgical technique was not possible owing to a lack of standardized technique nomenclature. Techniques are named but, are often modified (described and undescribed). Less than half the articles included descriptions and/or diagrams of the techniques used. This was further compounded by inconsistent reporting on the descriptions of surgical techniques among the studies and inadequate information to appropriately classify and compare techniques.

Limitations

Of note, VPI is not definitely a complication of palatoplasty owing to the natural incidence of VPI due to factors beyond the surgeon’s control, such as soft tissue availability, cleft width, and palatal length. These factors are highly variable and the most extreme severity may be impossible to overcome with a singular surgery. More data are needed to better understand the factors that contribute to the occurrence of VPI. Despite these inherent factors, this systematic review demonstrates that optimization of technique and timing may reduce VPI. Palatoplasty has been shown to improve articulation patterns, regardless of the presence of VPI. However, it is important to note that reducing VPI may not correct all aspects of speech development. VPI is one component of speech development and palatoplasty alone has been demonstrated to improve articulation patterns regardless of VPI.

The generalizability of our report relies on the quality and consistency of the underlying study data. Biases may result from retrospective studies and those that did not include details about blinding reviewers, speech assessment protocols, or surgical details. Furthermore, confounding factors such as surgeon expertise, and cleft severity and phenotype, were not analyzed due to inadequate data. Longitudinal data collection of patients who undergo palatoplasty is challenging owing to poor long-term follow-up and lack of standardized outcomes assessments and metrics. In 2001, the Eurocleft study found that 201 European cleft centers had 194 different protocols for the management of unilateral cleft palate alone.41 Speech outcomes were defined by rate of secondary surgery, VPI, or hypernasality instead of a standardized single measurement. As some surgeons or centers are more active in treating mild or moderate VPI, the rate of secondary surgery may not consistently represent speech outcomes. There was minimal individual patient-level data reported in the studies, so mean ages for entire cohorts were utilized and may be subject to outlier influences compared with other methods of central tendency. The high variability in operative age within the Q4 group may also contribute to the statistical differences seen between this group and Q2 and Q3. Furthermore, statistical power of included studies was highly variable owing to small sample sizes. More accurate data collected through further prospective studies is crucial to inform timing and technique of primary palatoplasty. The need for larger longitudinal studies was addressed by the creation of the Universal Parameters for Reporting Speech Outcomes, which was cited as a protocol in only in 5 studies.9,40,42–45

Although outside the scope of this paper, we cannot deny the role that hearing has on speech development. There is variable consensus in the literature on the extent to which this can impact speech or be a confounding factor for VPI. If we had a better understanding of the implications of palatoplasty on hearing and effusions, it may help to construct more sophisticated treatment algorithms. As future studies are planned, it would be ideal to include these factors to gain a more complete understanding of the implications of an important and common surgery.

Recommendations

The authors would recommend future studies on cleft palate repair include the following: (1) a thorough description of the surgical technique either through diagrams or narratives; (2) a standardized assessment of resonance and articulation after the Universal Parameters for Reporting Speech Outcomes completed by blinded speech language pathologists; and (3) a mean age of the study population stratified by surgical technique and cleft phenotype. Few included studies incorporated all these elements.9,43,46 Further recommendations include improved data collection methods facilitated by (1) standardized metrics of evaluation; (2) national audits completed by blinded speech language pathologists to report on speech outcome of each cleft center for further comparison between international centers; and (3) central and shared databases. In addition, the tendency for surgeons to only learn one palatoplasty technique is a limiting factor for comparison of surgical techniques as surgeon skill is a confounding factor for outcomes. In one study of this review, surgeons were taught a second technique to serve as a control against themselves.47 Despite the intention, there will still be a bias towards the technique the surgeon has more initial experience with, making this confounding factor difficult to account for. As technology evolves, opportunities to utilize artificial intelligence to help us more readily obtain results and impact treatment algorithms are an option but need to be well organized. Organizations such as Operation Smile have started to explore ways to evaluate speech through artificial intelligence to increase access to care low-resource settings. Further research on this topic is required.”

Velopharyngeal insufficiency is a complication that causes substantial morbidity and developmental delay as the child’s ability to communicate in both social and educational settings is impaired. This systematic review highlights the lack of high-powered, well-designed studies in primary cleft palate repair which limits our ability to understand optimal timing and techniques that would limit VPI occurrence. Furthermore, low-income and middle-income countries (86% of the world’s population) are highly under-represented in the literature. These gaps in the literature should be seen as an opportunity to answer an important question that could substantially reduce morbidity and improve quality of life. This paper should be viewed as a call-to-action to generate: (1) high-quality research from thoughtfully designed studies; (2) greater global representation; and (3) global consensus once the high-quality evidence has been reviewed. This consensus can only be encouraged through collaboration and working towards a common goal of ensuring best outcomes for patients requiring primary palatoplasty.

CONCLUSION

Palatoplasty is life-changing surgery; however, our study demonstrates that 20% of patients who undergo primary palatoplasty are at risk of developing VPI. Despite inherent factors that may be difficult to overcome in patients with cleft, such as cleft width, soft tissue availability, and palatal length, it is still important that we strive for optimal results for both technique and timing. Although earlier cleft palate repairs suggest diminished rates of VPI, optimal timing for primary palatoplasty cannot be concluded from this study. Similarly, our study did not uncover a statistically superior surgical technique to limit postoperative VPI, and could not account for important confounders, such as surgeon skill, cleft severity, and phenotype, owing to inadequate published data. This is further complicated by inconsistent nomenclature of techniques and the lack of widely accepted standardized protocols and outcomes metrics for cleft surgery. This study demonstrates the need to standardize technique classification and speech evaluation to improve data collection and analysis. Future studies based on more reliable data can inform palatoplasty timing and technique to minimize VPI, while accounting for the risk of midface hypoplasia.

REFERENCES 1. World Health Organization Registry Meeting of Craniofacial Anomalies, Mossey PA, Catilla EE, et al. Global registry and database on craniofacial anomalies : report of a WHO Registry Meeting on Craniofacial Anomalies. Geneva: World Health Organization; 2003. 2. Hughes CD, Babigian A, McCormack S, et al. The clinical and economic impact of a sustained program in global plastic surgery: valuing cleft care in resource-poor settings. Plast Reconstr Surg 2012;130:87e–94e 3. Alkire B, Hughes CD, Nash K, et al. Potential economic benefit of cleft lip and palate repair in sub-Saharan Africa. World J Surg 2011;35:1194–1201 4. Poenaru D, Lin D, Corlew S. Economic Valuation of the global burden of cleft disease averted by a large cleft charity. World J Surg 2016;40:1053–1059 5. Chao TE, Sharma K, Mandigo M, et al. Cost-effectiveness of surgery and its policy implications for global health: a systematic review and analysis. Lancet Glob Health 2014;2:e334–e345 6. Sainsbury D, Williams C, de Blacam C, et al. Non-interventional factors influencing velopharyngeal function for speech in initial cleft palate repair: a systematic review protocol. Syst Rev 2019;8:261 7. Stein MJ, Zhang Z, Fell M, et al. Determining postoperative outcomes after cleft palate repair: a systematic review and meta-analysis. J Plast Reconstr Aesthet Surg 2019;72:85–91 8. Fisher DM, Sommerlad BC. Cleft lip, cleft palate, and velopharyngeal insufficiency. Plast Reconstr Surg 2011;128:342e–360ee 9. Zhao S, Xu Y, Yin H, et al. Incidence of postoperative velopharyngeal insufficiency in late palate repair. J Craniofac Surg 2012;23:1602–1606 10. Witt PD, Wahlen JC, Marsh JL, et al. The effect of surgeon experience on velopharyngeal functional outcome following palatoplasty: is there a learning curve? Plast Reconstr Surg 1998;102:1375–1384 11. Sommerlad BC. A technique for cleft palate repair. Plast Reconstr Surg 2003;112:1542–1548 12. Salyer KE, Sng KW, Sperry EE. Two-flap palatoplasty: 20-year experience and evolution of surgical technique. Plast Reconstr Surg 2006;118:193–204 13. Kirschner RE, Wang P, Jawad AF, et al. Cleft-palate repair by modified Furlow double-opposing Z-plasty: the Children’s Hospital of Philadelphia experience. Plast Reconstr Surg 1999;104:1998–2010; discussion 1-4 14. Inman DS, Thomas P, Hodgkinson PD, et al. Oro-nasal fistula development and velopharyngeal insufficiency following primary cleft palate surgery--an audit of 148 children born between 1985 and 1997. Br J Plast Surg 2005;58:1051–1054 15. Ha S, Koh KS, Moon H, et al. Clinical outcomes of primary palatal surgery in children with nonsyndromic cleft palate with and without lip. Biomed Res Int 2015;2015:185459 16. Follmar KE, Yuan N, Pendleton CS, et al. Velopharyngeal insufficiency rates after delayed cleft palate repair: lessons learned from internationally adopted patients. Ann Plast Surg 2015;75:302–305 17. Zhang Z, Stein M, Mercer N, et al. Post-operative outcomes after cleft palate repair in syndromic and non-syndromic children: a systematic review protocol. Syst Rev 2017;6:52 18. Paranaiba LM, Almeida H, Barros LM, et al. Current surgical techniques for cleft lip-palate in Minas Gerais, Brazil. Braz J Otorhinolaryngol 2009;75:839–843 19. Agrawal K. Cleft palate repair and variations. Indian J Plast Surg 2009;42(Suppl):S102–S109 20. Schonmeyr B, Wendby L, Sharma M, et al. Limited chances of speech improvement after late cleft palate repair. J Craniofac Surg 2015;26:1182–1185 21. Rohrich RJ, Love EJ, Byrd HS, et al. Optimal timing of cleft palate closure. Plast Reconstr Surg 2000;106:413–421; quiz 22; discussion 23-5 22. Dorf DS, Curtin JW. Early cleft palate repair and speech outcome. Plast Reconstr Surg 1982;70:74–81 23. Haapanen ML, Rantala SL. Correlation between the age at repair and speech outcome in patients with isolated cleft palate. Scand J Plast Reconstr Surg Hand Surg 1992;26:71–78 24. Pasick CM, Shay PL, Stransky CA, et al. Long term speech outcomes following late cleft palate repair using the modified Furlow technique. Int J Pediatr Otorhinolaryngol 2014;78:2275–2280 25. Friede H, Enemark H. Long-term evidence for favorable midfacial growth after delayed hard palate repair in UCLP patients. Cleft Palate Craniofac J 2001;38:323–329 26. Mossey PA, Little J, Munger RG, et al. Cleft lip and palate. Lancet 2009;374:1773–1785 27. Schuster T, Rustemeyer J, Bremerich A, et al. Analysis of patients with a cleft of the soft palate with special consideration to the problem of velopharyngeal insufficiency. J Craniomaxillofac Surg 2013;41:245–248 28. Yao CA, Swanson J, Chanson D, et al. Barriers to reconstructive surgery in low- and middle-income countries: a cross-sectional study of 453 cleft lip and cleft palate patients in Vietnam. Plast Reconstr Surg 2016;138:887e–895ee 29. Kummer AW, Hosseinabad HH, Redle E, et al. Protocols for reporting speech outcomes following palatoplasty or velopharyngeal surgery: a literature review. Plast Reconstr Surg Glob Open 2019;7:e2151 30. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med 2009;6:e1000097 31. Nagengast E, Xepoleas M, Islip D, et al. Timing of primary cleft palate surgery and its association with postoperative velopharyngeal insufficiency: a systematic review. PROSPERO: International prospective register of systematic reviews. 2020. 32. Sullivan SR, Marrinan EM, LaBrie RA, et al. Palatoplasty outcomes in nonsyndromic patients with cleft palate: a 29-year assessment of one surgeon’s experience. J Craniofac Surg 2009;20(Suppl 1):612–616 33. Cleft AWK. Palate and Craniofacial Anomalies: Effects on Speech and Resonance, 3rd ed.. Clifton Park, NY: Cengage Learning; 2014 34. Lin KY, Black JS, Wang JS, et al. An outcome study of a 2-flap pushback palatoplasty used in the treatment of wide cleft palates. J Craniofac Surg 2015;26:620–624 35. Mahoney MH, Swan MC, Fisher DM. Prospective analysis of presurgical risk factors for outcomes in primary palatoplasty. Plast Reconstr Surg 2013;132:165–171 36. Chapman KL, Hardin-Jones MA, Goldstein JA, et al. Timing of palatal surgery and speech outcome. Cleft Palate Craniofac J 2008;45:297–308 38. Pai BCJ, Hung YT, Wang RSH, et al. Outcome of patients with complete unilateral cleft lip and palate: 20-year follow-up of a treatment protocol. Plast Reconstr Surg 2019;143:359e–367ee 39. Murthy J, Sendhilnathan S, Hussain SA. Speech outcome following late primary palate repair. Cleft Palate Craniofac J 2010;47:156–161 40. Luyten A, Bettens K, D’Haeseleer E, et al. The impact of palatal repair before and after 6 months of age on speech characteristics. Int J Pediatr Otorhinolaryngol 2014;78:787–798 41. Shaw WC, Semb G, Nelson P, et al. The Eurocleft project 1996-2000: overview. J Craniomaxillofac Surg 2001;29:131–140; discussion 41-2 42. Leclerc JE, Godbout A, Arteau-Gauthier I, et al. We can predict postpalatoplasty velopharyngeal insufficiency in cleft palate patients. Laryngoscope 2014;124:561–569 43. Xu H, Song Q, Zou Y, et al. The postoperative speech intelligibility evaluation of modified Z-plasty palatoplasty. J Craniofac Surg 2019;30:1264–1267 44. Doucet JC, Herlin C, Captier G, et al. Speech outcomes of early palatal repair with or without intravelar veloplasty in children with complete unilateral cleft lip and palate. Br J Oral Maxillofac Surg 2013;51:845–850 45. Henningsson G, Kuehn DP, Sell D, et al. Universal parameters for reporting speech outcomes in individuals with cleft palate. Cleft Palate Craniofac J 2008;45:1–17 46. Klinto K, Brunnegard K, Havstam C, et al. Speech in 5-year-olds born with unilateral cleft lip and palate: a Prospective Swedish Intercenter Study. J Plast Surg Hand Surg 2019;53:309–315 47. Williams WN, Seagle MB, Pegoraro-Krook MI, et al. Prospective clinical trial comparing outcome measures between Furlow and von Langenbeck Palatoplasties for UCLP. Ann Plast Surg 2011;66:154–163