An innovative method for manufacturing the Tuebingen palatal plate for infants with Robin sequence.

BACKGROUND: Robin sequence (RS) is characterized by mandibular micro- and retrognathia, glossoptosis, upper airway obstruction and optionally a cleft palate. With an incidence of 1:8000, it belongs to the so-called rare diseases; 30-50% of patients have RS as part of a syndrome. A comparatively well-studied treatment option is the Tuebingen Palatal Plate (TPP), which has proven effective in both, isolated and syndromic RS, but often requires multiple endoscopies for perfect fit and effectiveness. We report on a new method for fitting the TPP with only one session of nasopharyngeal endoscopy resulting in the plate being finished in one day. METHODS AND RESULTS: First, a prototype is produced, consisting of a traditional acrylic palatal part and a velar extension made of thermoplastic resin, usually measuring 10x40mm. Using polymerization, a scale is added to the posterior part of the extension to help with determining its optimal length during endoscopic evaluation. The extension is pre-bent in the dental laboratory to achieve an approximate shape. During endoscopy, the prototype can be adjusted to the infant's anatomy: first, the angulation is customized by controlled heating, bending and cooling of the thermoplastic spur. Second, the length of the spur is adapted by grinding its tip. Then the prototype is returned to the dental laboratory for completion; the final plate can be delivered to the patient on the same day. It acts by shifting the tongue into a more anterior position, thereby opening the airway and releasing upper airway obstruction, as well as by acting as a functional orthodontic appliance that stimulates mandibular growth through exerting pressure on the base of the tongue. CONCLUSIONS: With the thermoplastic spur presented here, a TPP can be produced within one day, requiring only one endoscopy. This approach may facilitate fabricating the TPP.

Mandibular growth in infants with Robin sequence treated with the Tübingen palatal plate.

BACKGROUND: Robin sequence (RS) is characterized by mandibular retrognathia, glossoptosis and upper airway obstruction. Whether mandibular catch-up growth may occur in RS is yet controversial. Our functional and less invasive treatment including the Tübingen Palatal Plate (TPP), early oral feeding and orofacial stimulation may promote mandibular catch-up growth. We evaluated the effect of the Tübingen Palatal Plate on mandibular growth, expressed by the Jaw index, sleep study results and weight gain in infants admitted with isolated and syndromic RS, born at or referred to our center between 6/2015 and 5/2018. METHODS: Retrospective analysis of our electronic patient database that included data on jaw index measurements, sleep study results and standard deviation (Z-)scores for weight. RESULTS: Of 31 patients referred for RS treatment (22 isolated, 9 syndromic), we had data on the above parameters, determined at admission, discharge and 3 months after discharge, in 20. Jaw index at admission and 3-month follow-up was 8.8 (6.3-11.3) and 2.1 (2.0-4.0), respectively (median (IQR); p < 0.0001). Mixed-obstructive apnea index (MOAI) decreased from 9.7 (4.8-24.2) to 0.0 (0-1.3; p < 0.002). No significant correlation was observed between MOAI and Jaw Index, but MOAI correlated with the Maxillary/Mandibular arch ratio (r = 0.58; p < 0.001). Z-scores for weight were similar at both time points at - 1.34 (- 1.76 - - 0.57) and - 1.50 (- 1.89 - - 0.54), while the proportion of infants requiring nasogastric tube feeding decreased from 84 to 8%. No infant had craniofacial surgery; one with syndromic RS required tracheostomy. CONCLUSION: These longitudinal cohort data suggest that the Tübingen Palatal Plate as used here may alleviate upper airway obstruction by promoting mandibular growth. TRIAL REGISTRATION: N.A.

Less invasive treatment of sleep-disordered breathing in children with syndromic craniosynostosis.

BACKGROUND: Infants and children with syndromic craniosynostosis (SCS), such as Apert-, Crouzon- or Pfeiffer syndrome, are prone to sleep disordered breathing (SDB) including obstructive sleep apnea and upper airway resistance syndrome (OSAS, UARS), potentially leading to tracheostomy. We modified the Tübingen Palatal Plate (TPP), an oral appliance with a velar extension effectively treating airway obstruction in Robin sequence, by attaching a tube to its velar extension to bridge the narrow pharyngeal airway in SCS patients. Here, we evaluated this treatment concept. METHODS: Our hospital's electronic patient files were searched for all children with a diagnosis of SCS admitted between 01/01/2004 and 31/12/2016. Children with isolated craniosynostosis were excluded. OSAS was defined as a mixed-obstructive apnea-hypopnea index (MOAHI) > 1, and UARS as more than 1 episode with nasal flow limitation/h, but absent OSAS. Children with a diagnosis of OSAS received the TPP and fiberoptic nasopharyngoscopy to assess the type of obstruction and to adjust the plate. Growth and weight gain, determined as standard deviation scores, were also evaluated before and during treatment. RESULTS: Of 34 patients included, 24 presented with SDB (19 OSAS, 5 UARS) and 27 had midface hypoplasia. Proportions of SDB were 78% in those with, and 22% in those without midface hypoplasia. In the OSAS group (n = 19), 13 patients were treated with palatal plates, with the remaining receiving continuous positive airway pressure, midface surgery or tracheal intubation. The MOAHI decreased across all children receiving palatal plate treatment from 14.6 (range 0.0-50.7) at admission to 0.9 (range 0.0-3.5) at discharge (p = 0.002). SDS for weight and body length also improved (p < 0.05 for weight and p = 0.05 for body length). Only one child required tracheostomy. CONCLUSION: Treatment of upper airway obstruction by a modified TPP in these children with SCS was shown to be mostly effective and safe. If confirmed in larger prospective studies, it may help to avoid more invasive interventions.

Multicenter study on the effectiveness of the pre-epiglottic baton plate for airway obstruction and feeding problems in Robin sequence.

BACKGROUND: Treatment of Robin sequence is often either invasive or of unproven effectiveness. The pre-epiglottic baton plate (PEBP) is a well-studied alternative, yet is not widely applied internationally. We report on a prospective 3-center cohort study investigating this treatment. Based on an agreed protocol, parents of infants with Robin sequence referred to participating centers were offered enrollment, which involved taking a maxillary cast followed by endoscopy to fit the plate and sleep studies to monitor its effectiveness. Recordings were centrally analyzed by sleep specialists blinded to timing and center. Primary outcome was the mixed-obstructive apnea index, defined as the number of such apneas/h of sleep; secondary outcomes included the desaturation index to <80% pulse oximeter saturation and weight gain. RESULTS: Of 75 infants referred, 49 could be included; 1 center failed to perform appropriate sleep studies. Within a mean hospitalization of 3 weeks, the mixed-obstructive apnea index decreased (median; interquartile range) from 15.9 (6.3-31.5) to 2.3 (1.2-5.4); it decreased further to 0.7 (0.1-2.4) in the 32 infants who had a successful 3-month follow-up sleep study performed. The desaturation index normalized (from 0.38 (0-2.7) to 0.0 (0-0.1)). Mean standard deviation score for weight remained unchanged between admission and follow-up, while the proportion of tube-fed infants decreased from 74 to 14%. CONCLUSIONS: This prospective multi-center cohort study confirms retrospective audits on the effectiveness of PEBP treatment in improving upper airway obstruction and feeding problems, the main clinical problems of infants with Robin sequence. International collaboration is required to compare this with other treatment approaches. TRIAL REGISTRATION: Number NCT02266043 , Registered 30/09/2014; registered partially retrospectively.

Treatment of infants with Syndromic Robin sequence with modified palatal plates: a minimally invasive treatment option.

BACKGROUND: Infants with Robin sequence (RS) suffer from upper airway obstruction (UAO) and feeding problems. We developed an oral appliance with a velar extension in combination with functional treatment and appropriate feeding techniques, which was proven effective in isolated RS. As the above problems are particularly challenging in syndromic RS, we set out to evaluate our treatment concept also in these patients. METHODS: We searched our electronic departmental database to identify all children admitted to our department between 01/01/2003 and 31/12/2009 because of syndromic RS. UAO was quantified by cardiorespiratory sleep studies performed before and during treatment with a modified palatal plate. This appliance consists of a palatal part, covering the hard palate as well as the alveolar ridges and the potential cleft, and a velar extension shifting the tongue in a more anterior position, thereby opening the pharyngeal airway. It is adjusted by fiberoptic nasopharyngoscopy and controlled by cardiorespiratory sleep studies. Obstructive sleep apnea was defined as a mixed obstructive sleep apnea index (MOAI) >3/h. Feeding modalities before and after treatment and weight gain, determined as standard deviation score, were also evaluated. RESULTS: Of 68 children meeting inclusion criteria, 56 completed treatment (46 of these being infants). Underlying diagnoses included craniofacial dysostosis (N = 13) and synostosis syndromes (N = 5), unspecified dysmorphic syndromes (N = 23) and miscellaneous rare conditions (N = 27). Median MOAI decreased from 8.5 (range 0.3-76.0) at admission to 1.1 (0.0-5.2) at discharge (p < 0.001). 51 children received only a TPP and 5 additionally continuous positive airway pressure (CPAP) or high-flow nasal cannula during sleep for mild residual OSA. Three children ultimately required tracheostomy. The number of exclusively gavage fed infants was reduced from 23 to 7. Conversely, the number of children fed exclusively by mouth increased from 18 to 30. Median SDS for weight decreased from -1.6 (-3.5-1.7) to -1.3 (-4.1-2.5). Twelve children had their treatment prematurely discontinued, e.g. due to laryngeal collapse/laryngomalacia. No patient died during treatment. CONCLUSION: Treatment of UAO and feeding problems in these children with syndromic RS by a modified palatal plate with a velar extension was shown to be effective and safe. If confirmed in prospective studies, it may help to avoid more invasive interventions.

Functional treatment of airway obstruction and feeding problems in infants with Robin sequence.

BACKGROUND: Robin sequence (RS), characterised by micrognathia/retrognathia and glossoptosis with or without cleft palate, presents with intermittent upper airway obstruction and feeding difficulties. Active intervention is required to reduce the risk of brain damage or sudden death. Most treatment options are poorly studied and/or invasive. Our group developed a functional approach including early feeding training and the pre-epiglottic baton plate (PEBP), an orthodontic appliance with a velar extension shifting the base of the tongue forward. PATIENTS AND METHODS: We evaluated the effect of this approach on sleep study results and early weight gain by searching our electronic patient database for infants with isolated RS, born at or referred to our department between 1 January 2003 and 31 December 2012 and treated with the PEBP. RESULTS: Of 122 patients identified, 360 overnight sleep study results, obtained at admission, prior to hospital discharge and 3 months postdischarge, were available (117 infants had complete data). These showed a decrease in the mixed-obstructive apnoea index from (median; IQR) 8.8 (2.1-19.7) to 1.8 (0.6-5.4); p<0.001 and 0.2 (0-1.3); p<0.001, respectively. Z-scores for weight improved from -0.7 (-1.39 to -0.24) upon admission to -0.5 (-0.90 to +0.02) at follow-up (p=0.02), accompanied by a decrease in the proportion of infants requiring nasogastric tube feeding from 66% to 8%. No infant required craniofacial surgery or tracheostomy. CONCLUSIONS: These longitudinal cohort data suggest that this functional approach may be an option to treat both, upper airway obstruction and feeding problems, in infants with isolated RS.

Three-Dimensional Normal Facial Growth from Birth to the Age of 7 Years.

BACKGROUND: With the advent of computer-assisted three-dimensional surface imaging and rapid data processing, oral and maxillofacial surgeons and orthodontists are enabled to analyze facial growth three dimensionally. Normative data, however, are still rare and inconsistent. The aim of the present study was to establish a valid reference system and to give normative data for facial growth. METHODS: Three-dimensional facial surface images were obtained from 344 healthy Caucasian children (aged 0 to 7 years). The images were put in correspondence by means of six landmarks close to the skull base (exocanthion, endocanthion, otobasion inferius). Growth curves for 21 landmarks were estimated in the three dimensions. RESULTS: Facial regions close to the skull base (orbit and ear) showed a biphasic growth pattern, with accelerated growth during the first year of life that subsided to a decreased and linear velocity thereafter. Landmarks on the nose, lips, and chin demonstrated either a curvilinear or a linear growth pattern. CONCLUSIONS: The rapid increase of the orbit and ear region in infancy is a secondary phenomenon to the rapid growth of the neurocranium during the first year of life. Thereafter, maxillary and mandibular growth prevails. The present study gives three-dimensional normative data for an expanded growth span between birth and childhood.

Three-dimensional assessment of facial development in children with unilateral cleft lip with and without alveolar cleft.

Children with cleft lip or cleft lip and alveolus represent a minor group in the cleft population. The aim of this study was to analyze the faces of these children. In a prospective, cross-sectional study, 344 healthy children and 30 children with cleft lip or cleft lip and alveolus were scanned three-dimensionally at the age of 0 to 6 years. Twenty-one standard anthropometric landmarks were identified, and the images were superimposed. Growth curves for normal facial development were calculated. The facial morphology of cleft children was compared with that of unaffected children.Facial morphology and growth in the transverse direction of the examined patients appeared broadened in all levels. Especially the nasal landmarks indicated a widening of the nose. The landmarks ac l, sbal l, sbal r, c l, sn l, and ls l differed significantly from unaffected children. In the sagittal and vertical dimensions, there was no significant difference compared with unaffected children.Our study demonstrates that surgical and orthodontic treatment can restore the vertical and sagittal dimensions of the face in children with cleft lip with and without alveolar clefts; however, the transverse dimension-especially the nose-remains too broad.

Urinary nucleosides as potential tumor markers evaluated by learning vector quantization.

Modified nucleosides were recently presented as potential tumor markers for breast cancer. The patterns of the levels of urinary nucleosides are different for tumor bearing individuals and for healthy individuals. Thus, a powerful pattern recognition method is needed. Although backpropagation (BP) neural networks are becoming increasingly common in medical literature for pattern recognition, it has been shown that often-superior methods exist like learning vector quantization (LVQ) and support vector machines (SVM). The aim of this feasibility study is to get an indication of the performance of urinary nucleoside levels evaluated by LVQ in contrast to the evaluation the popular BP and SVM networks. Urine samples were collected from female breast cancer patients and from healthy females. Twelve different ribonucleosides were isolated and quantified by a high performance liquid chromatography (HPLC) procedure. LVQ, SVM and BP networks were trained and the performance was evaluated by the classification of the test sets into the categories "cancer" and "healthy". All methods showed a good classification with a sensitivity ranging from 58.8 to 70.6% at a specificity of 88.4-94.2% for the test patterns. Although the classification performance of all methods is comparable, the LVQ implementations are superior in terms of more qualitative features: the results of LVQ networks are more reproducible, as the initialization is deterministic. The LVQ networks can be trained by unbalanced sizes of the different classes. LVQ networks are fast during training, need only few parameters adjusted for training and can be retrained by patterns of "local individuals". As at least some of these features play an important role in an implementation into a medical decision support system, it is recommended to use LVQ for an extended study.