Differences in analysis and treatment of upper airway obstruction in Robin sequence across different countries in Europe.

The goal of this study was to explore the availability of diagnostic and treatment options for managing upper airway obstruction (UAO) in infants with Robin Sequence (RS) in Europe. Countries were divided in lower- (LHECs, i.e., PPP per capita < $4000) and higher-health expenditure countries (HHECs, i.e., PPP per capita ≥ $4000). An online survey was sent to European healthcare professionals who treat RS. The survey was designed to determine the availability of diagnostic tools such as arterial blood gas analysis (ABG), pulse oximetry, CO2 analysis, polysomnography (PSG), and sleep questionnaires, as well as to identify the used treatment options in a specific center. Responses were received from professionals of 85 centers, originating from 31 different countries. It was equally challenging to provide care for infants with RS in both LHECs and HHECs (3.67/10 versus 2.65/10, p = 0.45). Furthermore, in the LHECs, there was less access to ABG (85% versus 98%, p = 0.03), CO2 analysis (45% versus 70%, p = 0.03), and PSG (54% versus 93%, p < 0.01). There were no significant differences in the accessibility concerning pulse oximetry, sleep questionnaires, home saturation monitoring, nasopharyngeal tubes, Tuebingen plates, and mandibular distraction.    Conclusion: This study demonstrates a large difference in available care for infants with RS throughout Europe. LHECs have less access to diagnostic tools in RS when compared to HHECs. There is, however, no difference in the availability of treatment modalities between LHECs and HHECs. What is Known: • Patients with Robin sequence (RS) require complex and multidisciplinary care. They can present with moderate to severe upper airway obstruction (UAO). There exists a large variety in the use of diagnostics for both UAO treatment indications and evaluations. In most cases, conservative management of UAO in RS is sufficient. Patients with UAO that persist despite conservative management ultimately need surgical intervention. To determine which intervention is best suitable for the individual RS patient, the level of UAO needs to be determined through diagnostic testing. • There is a substantial variation among institutions across Europe for both diagnostics and treatment options in UAO. A standardized, internationally accepted protocol for the assessment and management of UAO in RS could guide healthcare professionals in the timing of assessment and indications to prevent escalation of UAO. Creating such a protocol might be a challenge, as there are large financial differences between countries in Europe (e.g., health expenditure per capita in purchasing power parity in international dollars ranges from $600 to over $8500). What is New: • There is a substantial variation in the availability of objective diagnostic tools between European countries. Arterial blood gas analysis, CO2 analysis and polysomnography are not equally accessible for lower-healthcare expenditure countries (LHECs) compared to higher-healthcare expenditure countries (HHECs). These differences are not only limited to availability; there is also a difference in quality of these diagnostic tools. Surprisingly, there is no difference in access to treatment tools between LHECs and HHECs. • There is national heterogeneity in access to tools for diagnosis and treatment of RS, which suggests centralization of health care, showing that specialized care is only available in tertiary centers. By centralization of care for RS infants, diagnostics and treatment can be optimized in the best possible way to create a uniform European protocol and ultimately equal care across Europe. Learning what is necessary for adequate monitoring could lead to better allocation of resources, which is especially important in a low-resource setting.

The ontogeny of Robin sequence.

The triad of micrognathia, glossoptosis, and concomitant airway obstruction defined as "Robin sequence" (RS) is caused by oropharyngeal developmental events constrained by a reduced stomadeal space. This sequence of abnormal embryonic development also results in an anatomical configuration that might predispose the fetus to a cleft palate. RS is heterogeneous and many different etiologies have been described including syndromic, RS-plus, and isolated forms. For an optimal diagnosis, subsequent treatment and prognosis, a thorough understanding of the embryology and pathogenesis is necessary. This manuscript provides an update about our current understanding of the development of the mandible, tongue, and palate and possible mechanisms involved in the development of RS. Additionally, we provide the reader with an up-to-date summary of the different etiologies of this phenotype and link this to the embryologic, developmental, and genetic mechanisms.

Mortality in Robin sequence: identification of risk factors.

Although Robin sequence (RS) is a well-known phenomenon, it is still associated with considerable morbidity and even mortality. The purposes of this study were to gain greater insight into the mortality rate and identify risk factors associated with mortality in RS. We retrospectively reviewed all RS infants followed at the Wilhelmina Children's Hospital from 1995 to 2016. Outcome measurements were death and causes of death. The authors identified 103 consecutive RS infants with a median follow-up of 8.6 years (range 0.1-21.9 years). Ten of the 103 infants (10%) died at a median age of 0.8 years (range 0.1-5.9 years). Nine of these ten infants (90%) were diagnosed with an associated syndrome. Of these, seven infants died of respiratory insufficiency due to various causes (two related to upper airway obstruction). The other two syndromic RS infants died of arrhythmia due to hypernatremia and of West syndrome with status epilepticus. One isolated RS infant died of brain ischemia after MDO surgery. Cardiac anomalies were observed in 41% and neurological anomalies in 36%. The presence of a neurological anomaly was associated with a mortality rate of 40% versus 7% in infants with no neurological anomaly (p = 0.016), with an odds ratio of 8.3 (95% CI 1.4-49.0) for neurological anomaly versus no neurological anomaly. Mortality was 15% in infants with syndromic RS versus 2% in infants with isolated RS (p = 0.044). Mortality was not significantly associated with the presence of a cardiac anomaly, surgical treatment for severe respiratory distress in the neonatal period, or prematurity. CONCLUSION: RS represents a heterogeneous patient population and is associated with a high level of underlying syndromes. The present study reports a mortality rate of 10% significantly associated with syndromic RS and the presence of neurological anomalies. A multidisciplinary approach in all infants born with RS, including genetic testing and examination of neurological anomalies in a standardized way, is crucial to identify infants with underlying syndromes potentially associated with increased mortality. What is Known: • Reported mortality rates in Robin sequence vary from 2% to 26%. • Clinicians mainly focus on the morbidity of Robin sequence that includes respiratory complications due to upper airway obstruction in the period after birth. • Robin sequence represents a heterogeneous patient population and is associated with a high level of underlying syndromes. What is New: • The present study reports a mortality rate of 10% significantly associated with syndromic Robin sequence and the presence of neurological anomalies. • A multidisciplinary approach in all infants born with Robin sequence, including genetic evaluation and standardized workup for neurological anomalies, is crucial to identify infants with underlying syndromes potentially associated with increased mortality.

The innervation of the soft palate muscles involved in cleft palate: a review of the literature.

OBJECTIVE: Surgical techniques to obtain adequate soft palate repair in cleft palate patients elaborate on the muscle repair; however, there is little available information regarding the innervation of muscles. Improved insights into the innervation of the musculature will likely allow improvements in the repair of the cleft palate and subsequently decrease the incidence of velopharyngeal insufficiency. We performed a literature review focusing on recent advances in the understanding of soft palate muscle innervation. MATERIAL AND METHODS: The Medline and Embase databases were searched for anatomical studies concerning the innervation of the soft palate. RESULTS: Our literature review highlights the lack of accurate information about the innervation of the levator veli palatini and palatopharyngeus muscles. It is probable that the lesser palatine nerve and the pharyngeal plexus dually innervate the levator veli palatini and palatopharyngeus muscles. Nerves of the superior-extravelar part of the levator veli palatini and palatopharyngeus muscles enter the muscle form the lateral side. Subsequently, the lesser palatine nerve enters from the lateral side of the inferior-velar part of the levator veli palatini muscle. This knowledge could aid surgeons during reconstruction of the cleft musculature. The innervation of the tensor veli palatini muscle by a small branch of the mandibular nerve was confirmed in all studies. CONCLUSION: Both the levator veli palatini and palatopharyngeus muscles receive motor fibres from the accessory nerve (through the vagus nerve and the glossopharyngeal nerve) and also the lesser palatine nerve. A small branch of the mandibular nerve innervates the tensor veli palatini muscle. CLINICAL RELEVANCE: Knowledge about these nerves could aid the cleft surgeon to perform a more careful dissection of the lateral side of the musculature.

Long-term speech outcome in patients with Robin sequence after cleft palate repair and tongue-lip adhesion: A 21-year retrospective analysis.

The purpose of this study was to assess the effect of tongue-lip adhesion (TLA) on the long-term speech and articulation outcomes of patients with Robin sequence (RS) after cleft palate repair. Outcomes were compared to those in patients with RS who required positioning alone and to patients with isolated cleft palate (ICP). All consecutive patients with RS (with or without TLA) versus isolated cleft palate (ICP) who underwent cleft palate repair were retrospectively reviewed. Speech and articulation included all assessments between the age of 3-6 years. Secondary speech operations, velopharyngeal insufficiency (VPI), hypernasality, and articulation errors by cleft-type characteristics (CTC), including 4 categories (passive), non-oral, anterior-oral, and posterior-oral. A total of 41 RS patients and 61 ICP patients underwent repair with sufficient follow-up. Of them, 23 patients underwent a TLA at median age of 12 days. Rates of hypernasality (p = 0.004), secondary speech operations (p = 0.004), and posterior oral CTC (p = 0.042) were higher in RS compared to ICP. Isolated RS had speech outcomes similar to those of ICP; however, syndromic RS patients needed more secondary speech operations compared to isolated RS (p = 0.043). TLA-RS patients did not demonstrate differences in speech outcomes or any CTCs (all p > 0.05) compared to non-TLA-RS patients, except for the anterior oral CTC (74% TLA-RS vs 28% non-TLA-RS, p = 0.005). Within the limitations of the study, it seem that TLA does not affect long-term velopharyngeal function in patients with RS. However, TLA-RS patients demonstrated higher rates of anterior-oral CTC, which might be related to a different positioning of the tongue after TLA. Every effort should be taken to treat patients with RS conservatively instead of with TLA because of this demonstrated a negative effect on one type of articulation error. However, if conservative therapy fails, a TLA is still a valuable adjunct in the treatment of RS, and cleft speech pathologists who treat such patients should be more aware of this phenomenon in order to improve long-term articulation outcomes.

Advantages and disadvantages of mandibular distraction in Robin sequence.

Robin sequence (RS) is diagnosed in infants born with micrognathia, glossoptosis and varying degrees of upper airway obstruction (UAO). Due to the variable levels of hypoxia, severe breathing and feeding problems can occur. Treatment is determined by clinical severity, ranging from conservative interventions for mild cases to surgical interventions for severe cases. Mandibular distraction osteogenesis (MDO) is a surgical technique that gradually lengthens the mandible after an osteotomy by using an internal or external distraction device, directly correcting the micrognathia. This review will focus on advantages and disadvantages of mandibular distraction in infants with RS.

Long-term Speech Outcomes of Cleft Palate Repair in Robin Sequence versus Isolated Cleft Palate.

Whether treatment of cleft palate (CP) associated with Robin sequence (RS) should attain outcomes similar to those of isolated cleft palate (ICP) remains unknown. This study compares treatment and outcomes in both conditions and delineates predictors of long-term outcome. METHODS: This retrospective case series of consecutive syndromic and isolated RS- and ICP-patients (1990-2016) includes indications and outcomes of straight-line repair with intravelar veloplasty (SLIV) or Furlow repair depending on cleft and airway characteristics. RESULTS: Seventy-five RS and 83 ICP patients underwent CP repair. Velopharyngeal insufficiency (VPI) occurred in 41% of RS versus 17% of ICP patients (P = 0.012), and in 60% of patients with syndromic RS versus 16% with isolated RS (P = 0.005). In multivariable logistic regression analysis, wider and more severe CP anatomy was the only factor independently associated with VPI (P = 0.028), in contrast to age at repair, syndromic RS compared with isolated RS, and isolated RS compared with ICP and initial tongue-lip adhesion. Secondary Furlow after primary SLIV was used to treat VPI in all groups, and more frequently in syndromic versus isolated RS patients (P = 0.025). CONCLUSIONS: Variability of RS anatomy and airway compromise necessitates individualized treatment protocols. Despite differing CP etiology and other variables, our findings demonstrate cleft anatomy as the only independent variable predictive of VPI comparing RS and ICP patients. Patients with isolated RS should ultimately attain similar VPI outcomes compared with ICP patients. Obstructive speech operations in RS patients can be avoided without compromising speech outcome by reserving the prsocedure for secondary cases.

Objective measurements for upper airway obstruction in infants with Robin sequence: what are we measuring? A systematic review.

STUDY OBJECTIVES: Identifying optimal treatment for infants with Robin sequence (RS) is challenging due to substantial variability in the presentation of upper airway obstruction (UAO) in this population. Objective assessments of UAO and treatments are not standardized. A systematic review of objective measures of UAO was conducted as a step toward evidence-based clinical decision-making for RS. METHODS: A literature search was performed in the PubMed and Embase databases (1990-2020) following PRISMA guidelines. Articles reporting on RS and UAO treatment were included if the following objective measures were studied: oximetry, polysomnography, and blood gas. Quality was appraised by the methodological index for nonrandomized studies (range: 0-24). RESULTS: A total of 91 articles met the inclusion criteria. The mean methodological index for nonrandomized studies score was 7.1 (range: 3-14). Polysomnography was most frequently used (76%) followed by oximetry (20%) and blood gas (11%). Sleep position of the infant was reported in 35% of studies, with supine position most frequently, and monitoring time in 42%, including overnight recordings, in more than half. Of 71 studies that evaluated UAO interventions, the majority used polysomnography (90%), of which 61% did not specify the polysomnography technique. Reported polysomnography metrics included oxygen saturation (61%), apnea-hypopnea index (52%), carbon dioxide levels (31%), obstructive apnea-hypopnea index (27%), and oxygen desaturation index (16%). Only 42 studies reported indications for UAO intervention, with oximetry and polysomnography thresholds used equally (both 40%). In total, 34 distinct indications for treatment were identified. CONCLUSIONS: This systematic review demonstrates a lack of standardization, interpretation, and reporting of assessment and treatment indications for UAO in RS. An international, multidisciplinary consensus protocol is needed to guide clinicians on optimal UAO assessment in RS. CITATION: Logjes RJH, MacLean JE, de Cort NW, et al. Objective measurements for upper airway obstruction in infants with Robin sequence: what are we measuring? A systematic review. J Clin Sleep Med. 2021;17(8):1717-1729.

Assessment of Health-Related Quality of Life in Robin Sequence: A Comparison of Mandibular Distraction Osteogenesis and Tongue-Lip Adhesion.

BACKGROUND: Numerous studies have proven the efficacy of mandibular distraction osteogenesis or tongue-lip adhesion in Robin sequence infants with upper airway obstruction. However, none has compared health-related quality of life outcomes. METHODS: In the present retrospective study, Robin sequence infants younger than 1 year, who underwent mandibular distraction osteogenesis or tongue-lip adhesion, were included (2006 to 2016). The infants' caregivers were asked to complete a questionnaire based on the Glasgow Children's Benefit Inventory. RESULTS: The response rate was 71 percent (22 of the 31 questionnaires; mandibular distraction osteogenesis, 12 of 15; and tongue-lip adhesion, 10 of 16) and median age at surgery was 24 days (range, 5 to 131 days). Median total Glasgow Children's Benefit Inventory scores after mandibular distraction osteogenesis and after tongue-lip adhesion were 21.9 (interquartile range, 9.4) and 26.0 (interquartile range, 37.5), respectively (p = 0.716), indicating an overall benefit from both procedures. Positive changes were observed in all subgroups emotion, physical health, learning, and vitality. In syndromic Robin sequence, both procedures demonstrated a lower positive change in health-related quality of life compared with isolated Robin sequence (p = 0.303). CONCLUSIONS: Both surgical procedures demonstrated an overall benefit in health-related quality-of-life outcomes, with no significant differences. The authors' findings contribute to the debate regarding the use of mandibular distraction osteogenesis versus tongue-lip adhesion in the surgical treatment of Robin sequence; however, studies evaluating health-related quality of life in larger Robin sequence cohorts are necessary to identify which procedure is likely to be best in each individual Robin sequence infant. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Velopharyngeal insufficiency treated with levator muscle repositioning and unilateral myomucosal buccinator flap.

PURPOSE: Velopharyngeal insufficiency (VPI) is common (20-30%) after cleft palate closure. The myomucosal buccinator flap has become an important treatment option for velopharyngeal insufficiency; however, published studies all use bilateral buccinator flaps. This study assesses outcomes with a unilateral myomucosal buccinator flap that might result in less operating time and might prevent the need of a bite block and an extra procedure for division of the flap pedicle at a later stage. MATERIALS AND METHODS: Forty-two consecutive patients who underwent a unilateral myomucosal buccinator flap procedure were retrospectively reviewed. Overall clinical judgment of speech, speech analysis, and velopharyngeal closure were evaluated by a multidisciplinary cleft palate team. RESULTS: Median follow-up was 1.2 years. In 83% of patients, overall clinical judgment of optimal speech was obtained and thus no further velopharyngeal surgery was necessary. In 7 patients, further surgery was necessary, of whom 57% (4/7) had bilateral cleft lip-palate. Mean level of intelligibility improved significantly as evaluated by speech pathologists (2.5 ± 0.9 vs 3.5 ± 0.9; P < 0.0001) and by parents (2.1 ± 0.9 vs 3.2 ± 0.7; P < 0.0001). Mean level of resonance improved significantly (0.7 ± 0.9 vs 2.0 ± 1.0; P < 0.0001), and velopharyngeal closure improved in 83% postoperatively. CONCLUSION: The unilateral myomucosal buccinator flap seems to be an effective and safe procedure and should become part of the armamentarium of cleft surgeons.