The Treatment of Cleft Lip and Palate Deformities

Background: Cleft lip and palate deformities (CLPD) constitute one of the more common types of congenital malformation. In Germany, the prevalence is more than 1 in 500 births. The treatment is complex; multistep interdisciplinary treatment is needed for full recovery. In this S3-level clinical practice guideline, we provide evidence- and consensus-based recommendations for the treatment of patients with CLPD.

Methods: A systematic literature search based on key questions was carried out. All recommendations and statements were formulated by specialists from multiple disciplines and were adopted in a formal consensus procedure.

Results: Despite the epidemiological and clinical importance of CLPD, no clear treatment recommendations are available; the major treatments for it are debated and variably provided. If a fetus is at elevated risk of CLPD, ultrasonography in the second or third trimester of pregnancy is recommended. For a newborn child with CLPD, adequate food intake must be ensured. Orthodontic treatment is carried out in an interdisciplinary manner and in multiple developmental phases. Controversy surrounds the timing and sequence of reconstructive procedures for deformities that affect all structures. In children who have them, normal ventilation of the middle ear is impaired or obviated, making tympanic effusions and hearing loss more likely. In all children with CLPD, speech can be impaired and there can be a secondary impairment of language acquisition.

Conclusion: Most of the evidence concerning the treatment of CLPD is of low level. Standardization of the treatment approach should improve long-term outcomes and quality of life in patients with CLPD. Standardized, long-term, multicenter data acquisition would help increase the yield of useful information from future studies.

Cite this as: Sander AK, Muche-Borowski C, Lethaus B, on behalf of the guideline group “Treatment of Cleft Lip and Palate Deformities”: Clinical practice guideline: The treatment of cleft lip and palate deformities. Dtsch Arztebl Int 2025; 122: 328–33. DOI: 10.3238/arztebl.m2025.0052

With an estimated prevalence of 1 in 700 live births, cleft lip and palate deformities (CLPD) rank among the most common types of congenital malformation (1). The significant ethnical and geographic variations in prevalence rates are most likely attributable to genetic factors; with more than 1 in 500 live births, the prevalence in Germany appears to be particularly high compared to other European countries (1, 2).

A failure of fusion of the lateral maxillary prominences with the medial nasal prominence during embryological development results in CLPD. Depending on the affected anatomical subunits (upper lip, alveolar ridge/hard palate, soft palate) and the severity, the degree of deformity ranges from microforms (e.g. bifid uvula, lip notch) to bilateral complete deformities of the upper lip, nasal floor, alveolar ridge, hard palate, and soft palate. Overall, approximately 7% of orofacial malformations are observed as part of syndromes, and over 300 different superordinate syndromes are known. In approximately 16% of cases, associated deformities are found (3).

Thus, the severity of the deformity (Figure), complications and concomitant conditions have a decisive impact on an individual’s burden of disease. Except for individuals with microforms with no negative esthetic or functional consequences, all patients with cleft lip and palate deformities should be treated. In almost all cases, extensive interdisciplinary treatment effort is required to achieve full recovery (eBox 2). Usually, a two-stage approach is used for primary surgical repair of CLPD in the child’s first year of life. During the first procedure, reconstruction of the upper lip, nostril and nasal vestibule is performed, followed by reconstruction of the hard/soft palate during the second procedure. The mean length of postoperative hospital stay is slightly longer after cleft palate repair (4.5 ± 2.7 days) compared to cleft lip repair (4.1 ± 2.6 days) (4). The goal of CLPD treatment is to achieve esthetic and functional recovery so that the child is able to chew, speak and breathe normally by the time it reaches school age (Figure). Until completion of jaw and facial development, the interdisciplinary follow-up and management of these patients, which requires considerable time and effort, should be the standard of care.

Figure

Patient with cleft lip and palate deformity before (left) and after (right) primary surgical treatment

Figure

Overview of treatment steps

eBox 1

Collaborators

eBox 2

Specialist disciplines involved in treatment and corresponding fields of activity

Suboptimal treatment of patients with CLPD can lead to more severe language, speech and hearing disorders, permanent jaw and teeth misalignment, esthetic impairment and, ultimately, a reduction in well-being and social integration (Table). However, despite being highly relevant from an epidemiological and clinical point of view, CLPD treatment is currently not standardized and varies widely between different centers, both across Germany and internationally (4). In the experience of the authors of this article, case numbers per therapist can be very low in the outpatient sector, resulting in a lack of treatment routine.

Table

Impairments and complications associated with cleft lip and palate deformities

The aim of this clinical practice guideline is to provide evidence- and consensus-based information relevant to the treatment of patients with CLPD. The long-term outcome and quality of life of this patient population could be improved by standardizing CLPD treatment based on the current evidence.

Methods

The methods used to develop this S3-level clinical practice guideline are in line with those specified in The Guidance Manual and Rules for Guideline Development of the Association of the Scientific Medical Societies in Germany (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften) (5). The available evidence (eFigure) was evaluated based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework, using defined criteria (6). The evidence-based (EB) and consensus-based (expert consensus, EC) recommendations are created on the basis of a critical evaluation of the evidence as well as the clinical, practical care and ethical value judgments of the interdisciplinary guideline group. This group is made up of mandate holders of a total of 40 different medical societies and organizations (eBox 3).

eBox 3

Professional societies involved in the development of the guideline

eFigure

Flow chart of study selection according to current PRISMA guidelines

While an abundance of publications is available (eFigure) , the quality of evidence of the identified studies was mostly low. Due to methodological shortcomings, the quality of evidence of most of the few available randomized, controlled trials (RCTs) had to be rated as “low” or “very low”. In addition, the comparability of the study results is limited by a wide variation in study designs and defined endpoints. This constellation complicates the interpretation of the results. For this reason, all recommendations were extensively discussed by leading German experts in the respective fields and assessed based on their clinical expertise.

The recommendations on diagnosis and treatment

A total of 74 recommendations and 20 statements were adopted, of these 66 evidence- and 28 consensus-based.

Due to this large number, we can only present a few examples here. These roughly follow the successive steps. The complete guideline is available on the website of the Association of the Scientific Medical Societies in Germany (AWMF) (7).

Prenatal diagnosis

Prenatal ultrasound of the fetal face permits identification of a deformity as early as 14 weeks’ gestation. An article published in 2022 reported a sensitivity of 81.9 % and a specificity of 99.9% (positive predictive value: 80.1%; negative predictive value: 99.9 %) for the ultrasound detection of orofacial deformities (8). In a preselected risk group, the accuracy and differentiation of various types of deformities can be further improved by using the 3D technique. However, only about half of all CLPD cases are diagnosed prenatally.

On the one hand, a prenatally established diagnosis can give parents time to learn about the deformity and make the necessary preparations. On the other hand, an adequate prenatal diagnosis can lead to giving birth in a specialized hospital where optimum postnatal care can be provided, especially in cases with syndromic disease and associated deformities.

For patients at increased risk of having a child with CLPD, targeted ultrasound examinations aimed at providing detailed diagnostic insights in the second and third trimesters of pregnancy are recommended (EBR ↑↑, “should” recommendation).

Human genetic testing

The genetic background of non-syndromic CLPD is still not fully understood. In principle, however, genetic testing for syndromic diseases caused by chromosomal aberrations or single-gene mutations may be performed on all CLPD patients.

The presence of additional congenital anomalies is considered a strong predictor of syndromic disease. In these cases, the detection of a single-gene mutation or a chromosomal aberration allows a definite genetic diagnosis to be established and statements to be made about the prognosis, pattern of inheritance and the probability of recurrence in relatives and pregnancies. Currently, a pathogenic genetic variant can be identified in about 10% of patients primarily presenting as non-syndromic (9). If genetic testing in patients presenting as non-syndromic is negative, this finding supports a diagnosis of non-syndromic deformity.

Thus, the recommendation is to offer parents prenatal counseling and potentially further diagnostic testing by a clinical human geneticist, if additional malformations are detected by prenatal ultrasound. The same applies pre- and postnatally to patients with clinically non-syndromic CLPD and a positive family history (EBR↑, “ought to “ recommendation).

Nutrition

In children born with CLPD, it is of vital importance to ensure adequate food intake. In the case of isolated cleft lips, feeding is usually possible without problems. In contrast, in at least one third of newborns with deformities involving the palate, feeding is markedly impaired (10). As the result of the palatal deformity, it is difficult or impossible for these infants to create adequate suction, making breastfeeding difficult or even impossible. Based on the current literature, the various aids used to feed newborns with CLPD, such as special teats, finger feeding or squeezable bottles, are to be considered equally useful (11). Even though the available evidence is generally of low quality, it seems advisable to offer parents of children with CLPD prenatal counselling and postnatal feeding support by specially trained staff (EBR↑).

After primary surgical reconstruction, oral feeding is frequently temporarily stopped for fear of complications and a switch is made to, for example, nasogastric tube feeding. However, this fear appears to be unjustified, especially after cleft lip repair (12, 13). In patients with CLPD who underwent cleft lip repair, breastfeeding or bottle feeding ought to be resumed immediately after surgery (EBR↑). After surgical repair of a palatal cleft too, immediate postoperative oral feeding may be attempted under appropriate analgesia without any negative effect on the surgical outcome (EBR↔, “may“ recommendation).

Orthodontic treatment

Orthodontic treatment is an important element of the interdisciplinary management of patients with CLPD and of special importance in several developmental phases.

In patients with complete unilateral or bilateral CLPD, a removable so-called mouth/nose separator plate is fitted prior to primary reconstruction surgery. It corrects the position of the tongue and, with regular adjustments, supports the orientation of the maxillary segments. Despite a lack of supporting evidence, this method of passive orthodontic treatment is recommended based on expert consensus in order to facilitate primary surgical repair (EC↑).

In the case of alveolar ridge involvement, bone grafting is required for the repair of the osseous defect in order to enable the eruption of the permanent teeth and to stabilize the maxilla (alveolar cleft osteoplasty). This should be performed as a secondary alveolar cleft osteoplasty during the mixed dentition period (EC↑↑). The available literature does not allow to determine a definite superiority of autologous, allogeneic or xenogeneic augmentation material (14). Placement of autologous bone graft in the alveolar cleft area remains the gold standard compared to other materials used for augmentation and ought to be used preferentially until conclusive findings from studies of high methodological quality have become available (EC↑).

Surgical repair

A systematic review published in 2018 included all RCTs related to cleft surgery and craniofacial surgery (15). The authors were only able to identify 17 studies on the primary repair of CLPD that met the criteria for highest quality. Many of the standard surgical procedures in this field cannot be supported by high-quality evidence from RCTs. In addition, the existing, mostly single-center trials included only small numbers of cases, a fact that reduces the quality of the evidence.

To illustrate this problem, we will use the example of a unilateral cleft lip repair. There are no systematic reviews comparing different techniques for the primary surgical repair of cleft lip and nose with regard to both esthetic and functional outcomes. We identified several RCTs in which two surgical techniques were compared in respect to the achieved esthetic outcomes. However, the quality of the evidence of each of the individual studies was very low, making it difficult to interpret the results (16, 17, 18, 19, 20, 21, 22, 23). For example, the comparison of two very widely used surgical techniques—the Millard technique versus the Tennison-Randall technique—seems to show advantages of using the Millard technique with regard to the shape (RR, 0.5 [0.05; 5.2]) and thickness (RR, 0.54 [0.25; 1.15]) of the scar. In contrast, the Tennison/Randall technique can achieve a more esthetic shape and symmetry of the nostrils (RR, 1.31 [0.8; 2.15]), columella (RR, 1.38 [0.95; 2]), and Cupid‘s bow (bow-shaped vermillion border of the upper lip; RR, 3 [0.66; 13.61]) (16, 20). Ultimately, minor trends can be identified from the published data with a low degree of certainty; in most cases, the confidence in the evidence is not strong enough to support practical recommendations. Nevertheless, consensus-based recommendations, reduced to generally acceptable principles, were created to address these topics.For example, the timing and sequence of CLPD repair procedures for continuous types of deformities (single-stage versus two-stage; upper lip prior to palate or vice versa; hard and soft palate simultaneously or in several steps, etc.) is the subject of ongoing discussion. In Europa, there are only few centers that use a single-stage approach with simultaneous repair of lip, nostrils, hard palate and soft palate. According to the literature, a single-stage strategy is not inferior to multi-stage concepts (24, 25, 26, 27); thus, the recommendation for a single-stage or multi-stage approach remains open (EBR↔).

It is recommended to perform primary rhinoplasty for uni- and bilateral deformities at the time of upper lip and nostril repair (28) (EBR↑). Gingivoperiosteoplasty, as a primary alveolar cleft osteoplasty, can only be performed if the anatomical situation is ideal (29) (EBR↔). With regard to the audiological outcome, an early closure of a cleft palate before age one year may be of advantage; preference ought to be given to a technique with velar muscle reconstruction (30, 31) (EBR↑).

Otorhinolaryngology /pediatric audiology

The abnormal insertion of the velar muscles in patients with CLPD makes normal ventilation of the middle ear difficult or even impossible. In more than 90% of affected children, middle ear effusions are found by age six months (32). It is not uncommon that serous otitis media results in an initially unnoticed hearing loss and, if left untreated, in chronic otitis and delayed speech development. Even though the topic is highly relevant and multiple publications are available, the question of indication for and timing of ventilation tube placement remains undecided. The guideline makes an open timing recommendation on the placement of ventilation tubes before or during primary cleft repair (32, 33, 34) (EBR↔); however, prophylactic placement is not indicated (35). In the case of repeated ventilation tube placement, the use of permanent ventilation tubes ought to be considered (EC↑). In patients with CLPD and unremarkable newborn hearing screening, an audiological follow-up examination should be carried out no later than age nine months (EBR↑).

Speech therapy/logopedics and velopharyngeal insufficiency

In children with CLPD, speech can be impaired and there can be a secondary impairment of language acquisition. The orofacial changes primarily affect speech ability, mostly in the aspects of articulation and resonance.

In order to confirm the diagnosis of velopharyngeal insufficiency, video nasopharyngoscopy ought to be performed in addition to an auditory-perceptual tone of voice assessment (36, 37) (EBR↑). If intelligibility is impaired or if there are relevant impairments in age-appropriate language development, it is recommended to initiate speech therapy. It was found that this approach improved speech production in 75% of affected children to a clinically relevant degree (95% CI: [61%; 87%]) and that in 21% of the affected children speech production subsequently was on a level of peers (95% CI: [10%; 34%]) (38). According to the current literature, the linguistic-phonological and the motor-phonetic speech therapy approach can be regarded as equivalent; the choice ought to be made based on the specific disorder (EBR↑).

Anesthesiological aspects

Laryngoscopy for endotracheal intubation during anesthesia for primary repair of a CLPD ought to be performed, if possible, primarily using a video laryngoscope—especially in children aged less than one year (39) (EBR↑).

Infiltration of local anesthetics into the surgical site always seems to be useful in patients undergoing primary reconstructive surgery. For cleft lip repair procedures, the additional administration of an infraorbital nerve block (INB) is recommended (EBR↑). With an INB, significantly lower pain scores and longer anesthesia duration was found compared to placebo administration (40). Furthermore, a significant reduction in the need for postoperative opioid administration was noted (time to first opioid dose prolonged to 215.76 minutes, 95% CI: [83.26; 448.26], p<0.005; reduced overall need for opioid analgesics 0.2 mg/kg/d, 95% CI: [−0.20; –0.20], p<0.00001) (e1).

The duration and modality of postoperative monitoring—e.g., a planned admission to the pediatric ICU—should be based on individual patient factors, the speed and ease of the actual surgical procedure and the risk of occurrence of potentially life-threatening complications (EbE↑↑).

Dental therapy

Due to possible tooth misalignment, hypoplasia and missing teeth, intensive dental care is required. Tooth conservation is critical for the development of the upper jaw, so preventative care should be provided as soon as the primary dentition erupts.

Conclusion

The treatment of patients with CLPD is a field with a tradition which dates back centuries. It is characterized by a complexity and depth that in many cases do not allow for simple and all-encompassing statements. Although thousands of publications are available, many aspects remain controversial.

Study design problems include:

• the patient-specific severity of the deformity
• the lack of generally adopted variables for outcome assessment
• the low patient numbers per center at some sites
• the influence of the person providing treatment, and
• the need for long-term planning, because definitive functional and esthetic outcomes can only be assessed once growth has been completed..

The current S3-level clinical practice guideline is the first in German-speaking countries that attempts to translate the available body of evidence into treatment-relevant recommendations. Expert consensus was easily reached in many relevant areas. At the same time, the guideline also reveals existing evidence gaps in a number of areas. Examples of key research questions include surgical techniques, the timing and sequence of surgical correction procedures as well as the diagnosis and treatment of chronic hearing loss. More interdisciplinary, multicenter, long-term research projects, specifically including centers that use different concepts, are needed to further improve the treatment of patients with CLPD in Germany. National standards for treatment centers and centralized, standardized documentation could make this task much easier.

Funding

The project on which this article is based was financially supported by the Innovation Fund of the Federal Joint Committee (G-BA, Gemeinsamer Bundesauschuss) (funding code: 01VSF21008).

Conflict of interest statement

AS and BL received nonfinancial support from the German Society of Dentistry, Oral and Maxillofacial Medicine (DGZMK). The remaining author declares no conflict of interest.

Manuscript received on 29 January 2025, revised version accepted on 13 March 2025.

Clinical practice guidelines in the Deutsches Ärzteblatt, as in many other journals, are not subject to a peer review process, since clinical practice (S3 level) guidelines are texts which have already been evaluated, discussed, and broadly agreed upon multiple times by experts (peers).

Translated from the original German by Ralf Thoene, M.D.

Corresponding author
Dr. med. Dr.med. dent. Anna Katharina Sander

References

1. Mossey PA, Modell B: Epidemiology of oral clefts 2012: An international perspective. Front Oral Biol 2012; 16: 1–18

2. Schwenzer N, Ehrenfeld M (eds.): Mund-Kiefer-Gesichtschirurgie. Stuttgart: Georg Thieme Verlag 2011

3. IPDTOC Working Group: Prevalence at birth of cleft lip with or without cleft palate: Data from the International Perinatal Database of Typical Oral Clefts (IPDTOC). Cleft Palate Craniofac J 2011; 48: 66–81

4. Preidl RHM, Kesting M, Rau A: Perioperative management in patients with cleft lip and palate. J Craniofac Surg 2020; 31: 95–101

5. Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF): AWMF-Regelwerk „Leitlinien“. www.awmf.org/regelwerk/ (last accessed on 26 November 2024).

6. Atkins D, Best D, Briss PA, et al.: Grading quality of evidence and strength of recommendations. BMJ 2004; 328: 1490

7. DGMKG, DGZMK: Therapie der Lippen-Kiefer-Gaumenfehlbildungen: Langfassung. Version 1. https://register.awmf.org/de/leitlinien/detail/007–038 (last accessed on 28 January 2025).

8. Gai S, Wang L, Zheng W: Comparison of prenatal ultrasound with MRI in the evaluation and prediction of fetal orofacial clefts. BMC Med Imaging 2022; 22: 213

9. Wurfbain LF, Cox IL, van Dooren MF, et al.: Diagnostic gene panel testing in (non)-syndromic patients with cleft lip, alveolus and/or palate in the Netherlands. Mol Syndromol 2023; 14: 270–82

10. Reid J, Kilpatrick N, Reilly S: A prospective, longitudinal study of feeding skills in a cohort of babies with cleft conditions. Cleft Palate Craniofac J 2006; 43: 702–9

11. Penny C, McGuire C, Bezuhly M: A systematic review of feeding interventions for infants with cleft palate. Cleft Palate Craniofac J 2022; 59: 1527–36

12. Matsunaka E, Ueki S, Makimoto K: Impact of breastfeeding and/or bottle-feeding on surgical wound dehiscence after cleft lip repair in infants: a systematic review. J Craniomaxillofac Surg 2019; 47: 570–7

13. Ranzer M, Daniele E, Purnell CA: Perioperative management of cleft lip repair: a meta-analysis and clinical practice guideline. Cleft Palate Craniofac J 2021; 58: 1217–25

14. Motamedian SR, Mohaghegh S, Lakmazaheri E, Ahmadi N, Kouhestani F: Efficacy of regenerative medicine for alveolar cleft reconstruction: A systematic review and meta-analysis. Curr Stem Cell Res Ther 2022; 17: 446–65

15. Bekisz JM, Fryml E, Flores RL: A review of randomized controlled trials in cleft and craniofacial surgery. J Craniofac Surg 2018; 29: 293–301

16. Adetayo AM, Adetayo MO, Adeyemo WL, James OO, Adeyemi MO: Unilateral cleft lip: evaluation and comparison of treatment outcome with two surgical techniques based on qualitative (subject/guardian and professional) assessment. J Korean Assoc Oral Maxillofac Surg 2019; 45: 141–51

17. Amaratunga NA: A comparison of Millard’s and LeMesurier’s methods of repair of the complete unilateral cleft lip using a new symmetry index. J Oral Maxillofac Surg 1988; 46: 353–6

18. Deshmukh M, Vaidya S, Deshpande G, Galinde J, Natarajan S: Comparative evaluation of esthetic outcomes in unilateral cleft lip repair between the Mohler and Fisher Repair Techniques: a prospective, randomized, observer-blind study. J Oral Maxillofac Surg 2019; 77: 182.e1–e8

19. El Maghraby MF, Ghozlan NA, Ashry MH, Abouarab MH, Farouk A: Comparative study between Fisher anatomical subunit approximation technique and Millard rotation-advancement technique in unilateral cleft lip repair. Alexandria Journal of Medicine 2021; 57: 92–102

20. Gadre P: Comparison between Millard’s rotational advancement flap and Tennison-Randall flap techniques for surgical correction of unilateral cleft lip. Austin J Otolaryngol 2016; 3: 1081.

21. Holtmann B, Wray RC: A randomized comparison of triangular and rotation-advancement unilateral cleft lip repairs. Plast Reconstr Surg 1983; 71: 172–9

22. Shah SAH, Aslam MT, Zulfiqar MS, Mehmood T, Mehmood MT, Ahmed M: Comparison of outcomes of Millard’s rotational advancement flap and Fisher’s techniques for surgical correction of UCLD. PJMHS 2022; 16: 334–6

23. de Silva Amaratunga NA: Combining Millard’s and Cronin’s methods of unilateral cleft lip repair—a comparative study. Asian J Oral Maxillofac Surg 2004; 16: 5–9

24. Fudalej PS, Urbanova W, Klimova I, et al.: The slavcleft: a three-center study of the outcome of treatment of cleft lip and palate. Part 2: Dental arch relationships. J Craniomaxillofac Surg 2019; 47: 1092–5

25. Stebel A, Urbanová W, Klimova I, et al.: The slavcleft: a three-center study of the outcome of treatment of cleft lip and palate. Nasolabial appearance. PeerJ 2021; 9: e10631

26. Urbanova W, Klimova I, Brudnicki A, et al.: The slavcleft: a three-center study of the outcome of treatment of cleft lip and palate. Part 1: Craniofacial morphology. J Craniomaxillofac Surg 2016; 44: 1767–76

27. Kantar RS, Rifkin WJ, Cammarata MJ, et al.: Single-stage primary cleft lip and palate repair: A review of the literature. Ann Plast Surg 2018; 81: 619–23

28. Zelko I, Zielinski E, Santiago CN, Alkureishi LWT, Purnell CA: Primary cleft rhinoplasty: a systematic review of results, growth restriction, and avoiding secondary rhinoplasty. Plast Reconstr Surg 2023; 151: 452e–62e

29. El-Ashmawi NA, ElKordy SA, Salah Fayed MM, El-Beialy A, Attia KH: Effectiveness of gingivoperiosteoplasty on alveolar bone reconstruction and facial growth in patients with cleft lip and palate: a systematic review and meta-analysis. Cleft Palate Craniofac J 2019; 56: 438–53

30. Téblick S, Ruymaekers M, van de Casteele E, Nadjmi N: Effect of cleft palate closure technique on speech and middle ear outcome: A systematic review. J Oral Maxillofac Surg 2019; 77: 405.e1–e15

31. Azman A, Manuel AM: Otological outcome in cleft lip and palate children with middle ear effusion. Int J Pediatr Otorhinolaryngol 2020; 138: 110274

32. Felton M, Lee JW, Balumuka DD, Arneja JS, Chadha NK: Early placement of ventilation tubes in infants with cleft lip and palate: A systematic review. Otolaryngol Head Neck Surg 2018; 158: 459–64

33. Chang FL, Chen CH, Cheng HL, et al.: Efficacy of ventilation tube insertion with palatal repair for otitis media in cleft palate: Meta-analysis and trial sequential analysis. J Pers Med 2022; 12: 255

34. Stanton E, Kondra K, Brahme I, et al.: Tympanostomy tubes: Are they necessary? A systematic review on implementation in cleft care. Cleft Palate Craniofac J 2023; 60: 430–45

35. Ponduri S, Bradley R, Ellis PE, Brookes ST, Sandy JR, Ness AR: The management of otitis media with early routine insertion of grommets in children with cleft palate—a systematic review. Cleft Palate Craniofac J 2009; 46: 30–8

36. Paniagua LM, Signorini AV, Costa SSd, Collares MVM, Dornelles S: Velopharyngeal dysfunction: A systematic review of major instrumental and auditory-perceptual assessments. Int Arch Otorhinolaryngol 2013; 17: 251–6

37. Lam DJ, Starr JR, Perkins JA, et al.: A comparison of nasendoscopy and multiview videofluoroscopy in assessing velopharyngeal insufficiency. Otolaryngol Head Neck Surg 2006; 134: 394–402

38. Sand A, Hagberg E, Lohmander A: On the benefits of speech-language therapy for individuals born with cleft palate: A systematic review and meta-analysis of individual participant data. J Speech Lang Hear Res 2022; 65: 555–73

39. de Carvalho CC, Regueira SLPA, Souza ABS, et al.: Videolaryngoscopes versus direct laryngoscopes in children: Ranking systematic review with network meta-analyses of randomized clinical trials. Paediatr Anaesth 2022; 32: 1000–14

40. Pfaff MJ, Nolan IT, Musavi L, et al.: Perioperative pain management in cleft lip and palate surgery: A systematic review and meta-analysis of randomized controlled studies. Plast Reconstr Surg 2022; 150: 145e–56e

e1. Morzycki A, Nickel K, Newton D, Ng MC, Guilfoyle R: In search of the optimal pain management strategy for children undergoing cleft lip and palate repair: a systematic review and meta-analysis. J Plast Reconstr Aesthet Surg 2022; 75: 4221–32

e2. Buller M, Jodeh D, Qamar F, Wright JM, Halsey JN, Rottgers SA: Cleft palate fistula: A review. Eplasty 2023; 23: e7

e3. Vale F, Paula AB, Travassos R, et al.: Velopharyngeal insufficiency treatment in cleft palate patients: Umbrella review. Biomimetics (Basel) 2022; 7: 118

e4. de Blacam C, Smith S, Orr D: Surgery for velopharyngeal dysfunction: A systematic review of interventions and outcomes. Cleft Palate Craniofac J 2018; 55: 405–22

e5. Tache A, Maryn Y, Mommaerts MY: Need for velopharyngeal surgery after primary palatoplasty in cleft patients. A retrospective cohort study and review of literature. Ann Med Surg (Lond) 2021; 69: 102707

e6. Valtonen H, Dietz A, Qvarnberg Y: Long-term clinical, audiologic, and radiologic outcomes in palate cleft children treated with early tympanostomy for otitis media with effusion: a controlled prospective study. Laryngoscope 2005; 115: 1512–6

e7. Siikaluoma L: Hearing impairments in adults with cleft palate: A systematic scoping review. Bachelor thesis. University of Örebrö 2019.

e8. Jiang L, Zheng Y, Li N, et al.: Relapse rate after surgical treatment of maxillary hypoplasia in non-growing cleft patients: A systematic review and meta-analysis. Int J Oral Maxillofac Surg 2020; 49: 421–31

e9. Sharma VP, Bella H, Cadier MM, Pigott RW, Goodacre TEE, Richard BM: Outcomes in facial aesthetics in cleft lip and palate surgery: A systematic review. J Plast Reconstr Aesthet Surg 2012; 65: 1233–45

e10. Page MJ, McKenzie JE, Bossuyt PM, et al.: The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021; 372: n71