Minimally-invasive airway management and early cleft palate repair in infants born with Robin sequence.

The objective of this study was to report outcomes of early cleft palate repair in infants born with Robin sequence (RS). A retrospective case series in a tertiary referral paediatric hospital was carried out, examining a consecutive series of 69 infants born with RS and cleft palate. A minimally invasive approach was taken to upper airway obstruction, with liberal nasopharyngeal airway (NPA) and non-invasive ventilation (NIV) use, guided by sleep studies. The palate was repaired between 6 and 9 months with a modified Malek technique. The most frequently used airway adjunct (59.4% of patients) was an NPA and the median duration of use was 5.6 months. All patients underwent a modified Malek cleft palate repair at a median of 7 months of age. Overnight oximetry demonstrated higher mean oxygen saturation (SpO2) across the group from initial neonatal admission to discharge (median 96.5% (interquartile range [IQR] 95-98%) vs 97.45% (IQR 96.5-98%) (P = 0.2, N = 34). Of those with a cardiorespiratory polysomnogram, the obstructive apnoea-hypopnea index (OAHI) was significantly lower postoperatively (5.9 vs 2.8, P = 0.028). This study supports the use of non-surgical airway strategies and early cleft palate repair in infants born with RS and cleft palate.

A Systematic Review of the Efficacy of Haemostatic Interventions in Primary Cleft Palate Repair.

OBJECTIVE: To evaluate the effectiveness of adrenaline infiltration, topical adrenaline, systemic tranexamic acid, fibrin tissue sealants and alginate-based topical coagulants at reducing blood loss and post-operative bleeding in primary cleft palate repair. DESIGN: Systematic review according to PRISMA-P guidelines, using Covidence systematic review software to facilitate 3-stage screening and data extraction by two reviewers. SETTING: Academic cleft surgery center. INTERVENTIONS: Any peri-operative intervention to reduce intra-operative and post-operative bleeding. MAIN OUTCOME MEASURES: Estimated blood loss, rate of post-operative bleeding, rate of return to theatre for haemostasis. RESULTS: Sixteen relevant studies were identified, with a total of 1469 study participants. Nine studies examined efficacy of infiltrating vasoconstrictors and all concluded that 1:100,000-1:400,000 adrenaline infiltration reduced intra-operative blood loss, to the range of 12-60 ml. Secondary bleeding and re-operation for haemostasis were uncommon. Tranexamic acid was studied in five randomised controlled trials, two of which demonstrated a significant reduction in blood loss compared to a control group. Use of fibrin and gelatin sponge products was examined in 3 studies, all of which reported no or minimal bleeding, but did not have quantifiable outcome measures. CONCLUSIONS: Infiltration with vasoconstricting agents, administration of systemic tranexamic acid and application of fibrin sealants have a well-studied and favorable safety profile in pediatric cases, and likely contribute to the relatively low incidence of post-operative bleeding and intra-operative blood loss in primary cleft palate repair.

The case for the pharyngeal flap pharyngoplasty in the management of velopharyngeal dysfunction.

Velopharyngeal dysfunction (VPD) occurs when there is inadequate closure of the velopharyngeal sphincter during speech. An incompetent velopharyngeal sphincter may require surgical intervention to create a functional seal between the oropharynx and the nasopharynx during speech. To date, no single pharyngoplasty procedure has emerged as superior to another, and the comparison of results between studies has been limited by variation in outcomes reporting. Here, we use the newly defined Core Outcome Set for VPD (COS-VPD) to report a consecutive series of 109 patients managed with a midline pharyngeal flap and simultaneous dissection and repositioning of the velar muscles. The overall 30-day postoperative complication rate was 3.6% (4 out of 109 patients). At 12-month follow-up, 79.3% of patients experienced a statistically significant improvement in hypernasality. Seven patients (6.4%) developed obstructive sleep apnoea (OSA) postoperatively, and this was confirmed with polysomnography, with four (3.6%) patients requiring takedown of the pharyngeal flap. Seven patients in total (7.3%) required takedown of the pharyngeal flap and sphincter pharyngoplasty because of insufficient improvement of their VPD following the initial procedure. Patient-reported outcomes were investigated using the Velopharyngeal Effects on Life Outcome (VELO) instrument, and a mean total score of 74.5 out of 100 was recorded. We conclude that cleft surgeons should not be dissuaded by historical concerns about high rates of perioperative complications and OSA and should consider including the pharyngeal flap in their armamentarium when managing patients with VPD.

Core Outcome Set for Reporting Outcomes of Interventions for Velopharyngeal Dysfunction: Final Results of the COS-VPD Initiative.

OBJECTIVE: To date, the recording of outcomes of interventions for velopharyngeal dysfunction (VPD) has not been standardized. This makes a comparison of results between studies challenging. The aim of this study was to develop a core outcome set (COS) for reporting outcomes in studies examining the management of VPD. DESIGN: A two-round Delphi consensus process was used to develop the COS. PATIENTS, PARTICIPANTS: The expert Delphi panel comprised patients and caregivers of patients with VPD, surgeons and speech and language therapists specializing in cleft palate, and researchers with expertise in VPD. INTERVENTIONS: A long list of outcomes was derived from the published literature. In each round of a Delphi survey, participants were asked to score outcomes using the Grading of Recommendations, Assessment, Development, and Evaluations scale of 1 to 9, with 1 to 3 labeled "not important," 4 to 6 labeled "important but not critical," and 7 to 9 labeled "critical." MAIN OUTCOME MEASURE: Consensus criteria were specified a priori. Outcomes with a rating of 75% or more of the panel rating 7 to 9 and 25% or fewer rating 1 to 3 were included in the COS. RESULTS: A total of 31 core outcomes were identified from the Delphi process. This list was condensed to combine topic areas to produce a final COS of 10 outcomes, including both processes of care and patient-reported outcomes that should be considered for reporting in future studies of VPD. CONCLUSIONS: Implementation of the COS-VPD will facilitate consistency of outcomes data collection and comparison of results across studies.

Protocol for the development of a core outcome set for reporting outcomes of management of velopharyngeal dysfunction.

INTRODUCTION: Velopharyngeal dysfunction (VPD) is present in up to 40% of patients following cleft palate repair. Children with VPD display hypernasal speech, nasal air emission and are at a high risk for developing articulation disorders. The overall result is decreased intelligibility and acceptability of speech, as well as significant functional and social impairments. Although there are several surgical approaches for the management of children with VPD, standard treatment protocols have not been well defined. There is a need for a core outcome set (COS) to reduce outcome reporting bias and heterogeneity across studies of VPD. The COS-VPD Initiative is an international effort to establish a COS for the reporting of studies of the management of VPD. METHODS AND ANALYSIS: The study has been developed according to the Core Outcome Set-STAandards for Development standards for the design of a COS study and will be carried out according to the guidance of the Core Outcome Measures in Effectiveness Trials (COMET) initiative. A long list of clinical and patient-reported outcomes will be identified from a systematic review of the literature. A two-stage Delphi consensus process will be used to refine this list into a COS. An international panel of key stakeholders including patients, parents and multidisciplinary clinical and academic experts will be invited to participate in this process. Consensus criteria will be specified a priori and the steering group will ratify the final COS. ETHICS AND DISSEMINATION: The study has ethical approval through Children's Health Ireland at Crumlin Research and Ethics Committee, Ref: GEN/683/18. The study is registered with the COMET Initiative (http://www.cometinitiative.org/studies/details/1146?result=true). The COS will be disseminated by publication in the peer-reviewed literature, presentation at international research meetings and distribution to patient-representative organisations. This will facilitate the application of the COS in future studies of the management of VPD.

Descent of the human larynx: An unrecognized factor in airway distress in babies with cleft palate?

The intranarial epiglottis, a feature of all newborn mammals, allows suckling and breathing to continue almost simultaneously by separating an oral food stream from a nasal airstream. In contrast to other mammals, the human larynx descends in the neck between birth and six months, extending the distance between the caudal aspect of the soft palate and the cephalic tip of the epiglottis. The mechanism of airway protection changes from a pattern in which an upright epiglottis is grasped by an intact palatopharyngeal sphincter to one in which the epiglottis folds down over the laryngeal aditus and the adducted vocal folds. The comparative anatomy and anthropological literature describing laryngeal descent was reviewed. A series of MRI images were used to illustrate the normal descent of the human larynx, which take place in infants in the first six months of life. Based on this information, we hypothesize that a cleft palate, by interrupting the sphincter function of palatopharyngeus on a high neonatal epiglottis, precipitates a need for premature and rapid maturation of the neonate's airway protection pattern, particularly during feeding. This may explain why, even in the absence of Robin sequence, some babies with cleft palates suffer respiratory distress during feeding.

How reliable is the vomer flap in early hard palate repair?

Hard palate closure with a vomer flap at the time of lip repair has been widely adopted. A recent study by Deshpande et al. showed a high rate of failure of the vomer flap and led the authors to abandon the technique. We conducted a retrospective study of vomer flap healing in a consecutive series of cases performed by the senior author (D.O.). The case records of 71 patients who underwent repair of unilateral cleft lip and palate with a vomer flap at the time of lip repair were studied. Vomer flap healing was assessed and documented by the senior author at the time of definitive palate closure, and this was recorded. Adequate records were available for 66 cases. Twelve patients (18%) had associated syndromes and were included in the analysis. The median age at the time of lip and vomer flap repair was 3.5 months, and that at the time of palate repair was 8 months. At definitive palatoplasty, the vomer flap was intact in 62 patients (94%). Four patients (6%) had partial or complete failure of the vomer flap. All failures occurred in cases where the vomer flap was sutured directly to the nasal mucosa, a technique since abandoned in favour of double-breasting the flap to the raw surface of the oral mucosa. Five patients had incomplete healing of the palate following definitive palatoplasty, two of whom had a previous vomer flap failure. Contrary to Deshpande et al., we found the vomer flap to be highly reliable in closing the hard palate at the time of primary lip repair.

Patterns of orofacial clefting in the facial morphology of bats: a possible naturally occurring model of cleft palate.

A normal feature of the facial anatomy of many species of bat is the presence of bony discontinuities or clefts, which bear a remarkable similarity to orofacial clefts that occur in humans as a congenital pathology. These clefts occur in two forms: a midline cleft between the two premaxillae (analogous to the rare midline craniofacial clefts in humans) and bilateral paramedian clefts between the premaxilla and the maxillae (analogous to the typical cleft lip and palate in humans). Here, we describe the distribution of orofacial clefting across major bat clades, exploring the relationship of the different patterns of clefting to feeding mode, development of the vomeronasal organ, development of the nasolacrimal duct and mode of emission of the echolocation call in different bat groups. We also present the results of detailed radiographic and soft tissue dissections of representative examples of the two types of cleft. The midline cleft has arisen independently multiple times in bat phylogeny, whereas the paramedian cleft has arisen once and is a synapomorphy uniting the Rhinolophidae and Hipposideridae. In all cases examined, the bony cleft is filled in by a robust fibrous membrane, continuous with the periosteum of the margins of the cleft. In the paramedian clefts, this membrane splits to enclose the premaxilla but forms a loose fold laterally between the premaxilla and maxilla, allowing the premaxilla and nose-leaf to pivot dorsoventrally in the sagittal plane under the action of facial muscles attached to the nasal cartilages. It is possible that this is a specific adaptation for echolocation and/or aerial insectivory. Given the shared embryological location of orofacial clefts in bats and humans, it is likely that aspects of the developmental control networks that produce cleft lip and palate in humans may also be implicated in the formation of these clefts as a normal feature in some bats. A better understanding of craniofacial development in bats with and without clefts may therefore suggest avenues for research into abnormal craniofacial development in humans.

Repair of anterior cleft palate fistulae with cancellous bone graft: a simple technique that facilitates dental reconstruction.

BACKGROUND: Cleft palate fistulas of the anterior hard palate following previous repair are a challenging surgical problem. In addition to nasal regurgitation and potential adverse effects on speech, these fistulas may necessitate obturation with a removable dental prosthesis and can mitigate a fixed prosthodontic dental reconstruction. The authors present a method of repair using cancellous bone graft and only native palatal mucosa. METHODS: The authors carried out a retrospective review of 27 consecutive patients who underwent anterior palate fistula repair performed by a single surgeon over an 8-year period. RESULTS: The authors performed 29 fistula closure procedures using cancellous bone on 27 consecutive patients. Twenty-three (85 percent) of the initial 27 palatal fistula repairs in this study resulted in complete closure of the fistula. Two of the four patients who had incomplete closure went on to have a second operation using exactly the same technique, and complete closure was achieved. The remaining two patients in whom only partial closure was achieved were asymptomatic and no further treatment was necessary. All patients had an improvement in fistula symptoms after surgery. All patients who were using removable dentures/obturators were restored with fixed dental restorations supported by osseointegrated implants or fixed conventional bridges. CONCLUSIONS: This relatively simple method achieves reliable closure of most anterior hard palate fistulas and can be repeated if necessary. This technique removes the necessity of obturation of the defect with a removable prosthesis and in some cases facilitates the placement of dental implants.

Testing reported associations of genetic risk factors for oral clefts in a large Irish study population.

BACKGROUND: Suggestive, but not conclusive, studies implicate many genetic variants in oral cleft etiology. We used a large, ethnically homogenous study population to test whether reported associations between nonsyndromic oral clefts and 12 genes (CLPTM1, CRISPLD2, FGFR2, GABRB3, GLI2, IRF6, PTCH1, RARA, RYK, SATB2, SUMO1, TGFA) could be confirmed. METHODS: Thirty-one single nucleotide polymorphisms (SNPs) in exons, splice sites, and conserved non-coding regions were studied in 509 patients with cleft lip with or without cleft palate (CLP), 383 with cleft palate only (CP), 838 mothers and 719 fathers of patients with oral clefts, and 902 controls from Ireland. Case-control and family-based statistical tests were performed using isolated oral clefts for the main analyses. RESULTS: In case-control comparisons, the minor allele of PTCH1 A562A (rs2066836) was associated with reduced odds of CLP (odds ratios [OR], 0.29; 95% confidence interval [CI], 0.13-0.64 for homozygotes), whereas the minor allele of PTCH1 L1315P (rs357564) was associated with increased odds of CLP (OR, 1.36; 95% CI, 1.07-1.74 for heterozygotes; and OR, 1.56; 95% CI, 1.09-2.24 for homozygotes). The minor allele of one SUMO1 SNP, rs3769817 located in intron 2, was associated with increased odds of CP (OR, 1.45; 95% CI, 1.06-1.99 for heterozygotes). Transmission disequilibrium was observed for the minor allele of TGFA V159V (rs2166975) which was over-transmitted to CP cases (p = 0.041). CONCLUSIONS: For 10 of the 12 genes, this is the largest candidate gene study of nonsyndromic oral clefts to date. The findings provide further evidence that PTCH1, SUMO1, and TGFA contribute to nonsyndromic oral clefts.

Folate-related gene polymorphisms as risk factors for cleft lip and cleft palate.

BACKGROUND: Cleft lip with or without cleft palate (CLP) and cleft palate only (CPO) have an inherited component and, many studies suggest, a relationship with folate. Attempts to find folate-related genes associated with clefts have, however, often been inconclusive. This study examined four SNPs related to folate metabolism (MTHFR 677 C-->T, MTHFR 1298 A-->C, MTHFD1 1958 G-->A, and TC II 776 C-->G) in a large Irish population to clarify their relationship with clefts. METHODS: Cases and their parents were recruited from major surgical centers performing cleft repairs in Ireland and a support organization. Data on risk factors, medical history, and DNA were collected. Controls were pregnant women from the greater Dublin area (n = 1,599). RESULTS: CLP cases numbered 536 and CPO cases 426 after exclusions. CPO mothers were significantly more likely than controls to be MTHFR 677 TT, OR 1.50 (95% CI: 1.05-2.16; p = .03). Log-linear analysis showed a borderline association (p = .07). Isolated CPO case mothers were significantly more likely than controls to be homozygous for the MTHFD1 1958 G-->A variant, OR 1.50 (95%CI: 1.08-2.09; p = .02). When multiple cases were added, both CPO cases and case mothers were significantly more likely to be AA (p = .02 and p = .007, respectively). The CLP case-control and mother-control analyses also showed significant effects, ORs 1.38 (95% CI: 1.05-1.82; p = .03) and 1.39 (95% CI: 1.04-1.85; p = .03), respectively. CONCLUSIONS: Associations were found for both CPO and CLP and MTHFD1 1958 G-->A in cases and case mothers. MTHFR 677 C-->T could be a maternal risk factor for clefts but the association was not strong. Because multiple comparisons were made, these findings require additional investigation. Given the known association between MTHFD1 1958 G-->A and NTDs, these findings should be explored in more detail.