Airway and Feeding Outcomes in Pierre Robin Sequence: A Comparison of Three Management Strategies.

BACKGROUND: Controversy remains regarding optimal management of Pierre Robin sequence (PRS). The goal of this study was to compare airway and feeding outcomes in infants with PRS who underwent surgical intervention, specifically mandibular distraction osteogenesis (MDO) or tongue-lip adhesion (TLA), or who had conservative management (CM) without surgery. METHODS: All consecutive patients treated for PRS at a pediatric academic medical center, with at least one year follow-up, were included. Patients who underwent tracheostomy as an index procedure were excluded. Patients were divided into those who underwent MDO, TLA or CM. Feeding status and data from initial and follow-up polysomnograms were collected. Comparisons between groups were made using the Kruskal-Wallis test, followed by Mann-Whitney pairwise comparison with a Bonferroni correction, when appropriate. RESULTS: 67 neonates were included. 19 underwent TLA, 29 underwent MDO and 19 underwent CM. The proportions of syndromic patients were similar between groups. Patients undergoing CM had the lowest baseline AHI (9.1), but there were no significant differences between TLA (20.1) and MDO (25.4). At follow-up, the three groups had similar mean AHI (MDO 1.3, TLA 4.2, CM 4.5). A similar proportion of patients achieved AHI 5 or less (TLA 89.5%, MDO 96.6%, CM 84.2%). At one year, there were no significant differences in weight percentiles or in risk of failure-to-thrive between groups. One patient from the TLA group required a tracheostomy. CONCLUSION: The three treatment modalities achieved high airway and feeding success rates. All three modalities should have a place in the armamentarium of the craniofacial surgeon.

Airway and Feeding Outcomes of Mandibular Distraction, Tongue-Lip Adhesion, and Conservative Management in Pierre Robin Sequence: A Prospective Study.

BACKGROUND: Pierre Robin sequence is characterized by mandibular retrognathia and glossoptosis resulting in airway obstruction and feeding difficulties. When conservative management fails, mandibular distraction osteogenesis or tongue-lip adhesion may be required to avoid tracheostomy. The authors' goal was to prospectively evaluate the airway and feeding outcomes of their comprehensive approach to Pierre Robin sequence, which includes conservative management, mandibular distraction osteogenesis, and tongue-lip adhesion. METHODS: A longitudinal study of newborns with Pierre Robin sequence treated at a pediatric academic medical center between 2010 and 2015 was performed. Baseline feeding and respiratory data were collected. Patients underwent conservative management if they demonstrated sustainable weight gain without tube feeds, and if their airway was stable with positioning alone. Patients who required surgery underwent tongue-lip adhesion or mandibular distraction osteogenesis based on family and surgeon preference. Postoperative airway and feeding data were collected. RESULTS: Twenty-eight patients with Pierre Robin sequence were followed prospectively. Thirty-two percent had a syndrome. Ten underwent mandibular distraction osteogenesis, eight underwent tongue-lip adhesion, and 10 were treated conservatively. There were no differences in days to extubation or discharge, change in weight percentile, requirement for gastrostomy tube, or residual obstructive sleep apnea between the three groups. No patients required tracheostomy. The greatest reduction in apnea-hypopnea index occurred with mandibular distraction osteogenesis, followed by tongue-lip adhesion and conservative management. CONCLUSIONS: Careful selection of which patients with Pierre Robin sequence need surgery, and of the most appropriate surgical procedure for each patient, can minimize the need for postprocedure tracheostomy. A comprehensive approach to Pierre Robin sequence that includes conservative management, mandibular distraction osteogenesis, and tongue-lip adhesion can result in excellent airway and feeding outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

The Children's Hospital of Philadelphia modification of the Furlow double-opposing z-palatoplasty: long-term speech and growth results.

Of the 261 nonsyndromic patients we studied, over 90% had minimal or absent hypernasality, almost 86% had inconsistent or no nasal emission, and 95% had no articulation errors related to velar function. The patients with a Pittsburgh score indicating an incompetent velopharyngeal mechanism comprised only about 6% of the group. Ninety-four percent had a socially functional speech quality. Secondary surgery was done in 6.5% of patients and was done or was recommended in about 8% of patients. Patients with isolated cleft palate seemed to do less well, although their outcomes were not statistically different from those with complete unilateral and bilateral clefts. Relaxing incisions have kept our fistula rate to an acceptably low rate of 6.8%. No major soft palate dehiscences or hard palate flap losses have occurred. The speech outcomes we are achieving are improved over our historical results and compared with published reports using nondouble reversing z-palatoplasty techniques. Similar outcomes with the Furlow repair have been confirmed. Maxillary growth, occlusion, and the need for orthognathic surgery do not seem to be influenced by the CHOP modification of the Furlow double-opposing z-palatoplasty. These modifications facilitate a tension free-closure and a low fistula rate.

Applications of a new carbonated calcium phosphate bone cement: early experience in pediatric and adult craniofacial reconstruction.

Hydroxyapatite cements have recently been employed as bone substitutes in craniofacial reconstruction. They are easily applied, nonresorbable, available in unlimited quantity, and eliminate donor-site morbidity. Norian CRS (craniofacial repair system) is a new carbonated calcium phosphate paste that is unique in that it more closely resembles bone than do traditional hydroxyapatite pastes. Norian is a low-order crystalline apatite soluble at a low pH, facilitating its resorption and replacement by host bone. The cement was first used for craniofacial surgery in North America at the Children's Hospital of Philadelphia. This report presents the authors' experience with this bone substitute in both pediatric and adult craniofacial reconstruction. Sixteen adult and pediatric patients underwent craniofacial reconstruction involving the use of carbonated calcium phosphate paste for correction of defects that required from 5 to 110 g of carbonated calcium phosphate paste (mean, 28.5 g). The patients were all followed for a minimum of 14 months. Minor complications included one case of infection and two cases involving cement microfragmentation. In the authors' experience, carbonated calcium phosphate paste has proved to be an excellent alloplastic material for osseous augmentation and reconstruction in the craniofacial skeleton. Few problems were encountered using this material; no significant morbidity was encountered. Although this material seems to be promising as a bone substitute, further follow-up will be necessary to evaluate its potential role in craniofacial surgery.

Surgical considerations in 22Q11.2 deletion syndrome.

The 22q11.2 deletion syndrome (22q11DS) may be associated with several palatal abnormalities, including overt cleft palate, submucosal cleft palate, palatopharyngeal disproportion, and velar hypotonia. The syndrome is the genetic disorder most commonly associated with velopharyngeal dysfunction (VPD). The complex causes of VPD in affected patients combine with the complexity of associated medical disorders to render surgical management of the velopharynx particularly challenging. Optimization of surgical outcomes requires precision in diagnosis, surgical management, and multidisciplinary care. This article provides an overview of 22q11DS and provides a review of the assessment and surgical management of VPD in affected individuals.

Submucosal injection of micronized acellular dermal matrix: analysis of biocompatibility and durability.

BACKGROUND: Posterior pharyngeal augmentation is a recognized treatment for velopharyngeal insufficiency in selected candidates. To date, however, the procedure has failed to gain widespread acceptance because of the absence of an implant material with sufficient safety, durability, and biocompatibility. In this study, the use of micronized acellular dermal matrix injection for augmentation of the posterior pharynx was investigated. Using a porcine animal model, the safety and durability of posterior pharyngeal augmentation by micronized decellularized dermis was evaluated. METHODS: Twelve Yorkshire piglets were used in this study. Under general anesthesia, porcine-derived micronized acellular dermal matrix was injected into the submucosa of the right side of the pharynx. At 30 days, the animals were euthanized, and the implants and surrounding tissues were assessed grossly for degree of augmentation and histologically to determine the extent of host cell infiltration, vascularization, and matrix deposition and remodeling. RESULTS: No animal perioperative or postoperative morbidity resulted from the operations. When the animals were euthanized and the tissue was harvested at 30 days, there existed no evidence of gross augmentation on the experimental side of the pharynx in any of the specimens. Histologic analysis demonstrated trace amounts of residual implant, with extensive host lymphocytic infiltration of the material. CONCLUSIONS: Although micronized acellular dermal matrix is a safe material when injected into the pharyngeal wall, this study demonstrated that it is not a durable implant at this site. The authors do not recommend its use for long-term soft-tissue augmentation of the posterior pharyngeal wall in patients with velopharyngeal insufficiency.

Evaluation of potential modifiers of the palatal phenotype in the 22q11.2 deletion syndrome.

OBJECTIVE: To evaluate potential modifiers of the palatal phenotype in individuals with the 22q11.2 deletion syndrome. DESIGN: Data from 356 subjects enrolled in a study of the 22q11.2 deletion syndrome were used to evaluate potential modifiers of the palatal phenotype. Specifically, subjects with and without velopharyngeal inadequacy and/or structural malformations of the palate were compared with respect to gender, race, and genotype for variants of seven genes that may influence palatal development. METHODS: The chi-square test or Fisher exact test was used to evaluate the association between palatal phenotype and each potential modifier. Odds ratios and their associated 95% confidence intervals were used to measure the magnitude of the association between palatal phenotype, subject gender and race, and each of the bi-allelic variants. RESULTS: The palatal phenotype observed in individuals with the 22q11.2 deletion syndrome was significantly associated with both gender and race. In addition, there was tentative evidence that the palatal phenotype may be influenced by variation within the gene that encodes methionine synthase. CONCLUSIONS: Variation in the palatal phenotype observed between individuals with the 22q11.2 deletion syndrome may be related to personal characteristics such as gender and race as well as variation within genes that reside outside of the 22q11.2 region.

Velopharyngeal anatomy in 22q11.2 deletion syndrome: a three-dimensional cephalometric analysis.

OBJECTIVE: 22q11.2 deletion syndrome is the most common genetic cause of velopharyngeal dysfunction (VPD). Magnetic resonance imaging (MRI) is a promising method for noninvasive, three-dimensional (3D) assessment of velopharyngeal (VP) anatomy. The purpose of this study was to assess VP structure in patients with 22q11.2 deletion syndrome by using 3D MRI analysis. DESIGN: This was a retrospective analysis of magnetic resonance images obtained in patients with VPD associated with a 22q11.2 deletion compared with a normal control group. SETTING: This study was conducted at The Children's Hospital of Philadelphia, a pediatric tertiary care center. PATIENTS, PARTICIPANTS: The study group consisted of 5 children between the ages of 2.9 and 7.9 years, with 22q11.2 deletion syndrome confirmed by fluorescence in situ hybridization analysis. All had VPD confirmed by nasendoscopy or videofluoroscopy. The control population consisted of 123 unaffected patients who underwent MRI for reasons other than VP assessment. INTERVENTIONS: Axial and sagittal T1- and T2-weighted magnetic resonance images with 3-mm slice thickness were obtained from the orbit to the larynx in all patients by using a 1.5T Siemens Visions system. OUTCOME MEASURES: Linear, angular, and volumetric measurements of VP structures were obtained from the magnetic resonance images with VIDA image-processing software. RESULTS: The study group demonstrated greater anterior and posterior cranial base and atlanto-dental angles. They also demonstrated greater pharyngeal cavity volume and width and lesser tonsillar and adenoid volumes. CONCLUSION: Patients with a 22q11.2 deletion demonstrate significant alterations in VP anatomy that may contribute to VPD.

Repair of the immature and mature craniofacial skeleton with a carbonated calcium phosphate cement: assessment of biocompatibility, osteoconductivity, and remodeling capacity.

BACKGROUND: The apatite compounds used most commonly in craniofacial reconstruction are highly crystalline and biologically inert ceramics. Because their capacity to be replaced by native bone is limited, they have found little application in repair of the growing craniofacial skeleton. Carbonated calcium phosphate cements more closely resemble the mineral phase of bone, thereby offering enhanced bioresorption and osteoconductivity, but their fate in the immature and mature craniofacial skeleton has not been investigated. METHODS: The authors hypothesized that the capacity for cell-mediated remodeling of carbonated calcium phosphate cements is based on (1) their crystallographic and compositional similarity to the mineral phase of bone and (2) the osteogenic capacity of the host. Four noncritical-sized calvarial defects were created in six 3-week-old and six 16-week-old Yorkshire pigs. The defects were repaired with autologous bone, sintered carbonated calcium phosphate cement disks with a higher crystal order, or carbonated calcium phosphate cement (Norian CRS; Synthes Maxillofacial, West Chester, Pa.). The fourth defect was left empty as a control. Specimens were harvested at 30 and 90 days postoperatively. RESULTS: Empty defects healed with dense fibroconnective tissue in all groups. Autologous bone grafts underwent complete remodeling and replacement with woven bone at both time points. Sintered carbonated calcium phosphate disks demonstrated no bony ingrowth or remodeling. In immature animals, carbonated calcium phosphate cement implants were progressively replaced with woven bone through osteoclast-mediated resorption and osteoblast-mediated bone formation. Only minimal remodeling of the carbonated calcium phosphate cement implants was observed in skeletally mature animals. CONCLUSIONS: The results of these experiments suggest that the extent of remodeling of carbonated calcium phosphate cement is dependent on both the composition of the implant itself and the osteogenic capacity of the host and that carbonated calcium phosphate cement may be used successfully for inlay applications in the immature craniofacial skeleton.

Reconstruction of the immature craniofacial skeleton with a carbonated calcium phosphate bone cement: interaction with bioresorbable mesh.

Calcium phosphate cements have been recently introduced for use in craniofacial reconstruction. In the clinical setting, however, pulsations of the underlying brain and dura may interfere with the crystallization of these cements, thereby rendering their use in cranioplasty problematic. To circumvent such problems, many clinicians have interposed synthetic resorbable plates or mesh between the dura and the cement. At the present time, however, little is known about the influence of such materials or their breakdown products on the fate of calcium phosphate cements. The specific aim of this project was to evaluate the biocompatibility, osteoconductivity, and remodeling capacity of a calcium phosphate cement after implantation into experimental calvarial defects when combined with a resorbable mesh underlay. Four 10-mm diameter full-thickness calvarial defects (two frontal, two parietal) were created in each of six 3-week-old Yorkshire pigs. The defects were treated as follows: 1) empty control, 2) macroporous polylactic acid (70/30 L/DL polylactic acid [PLA]) mesh, 3) Norian CRS calcium phosphate cement, and 4) Norian CRS over PLA mesh underlay. Animals were divided into two groups. Half of the animals were killed 30 days after surgery, and half were killed 180 days after surgery, and the graft recipient sites were examined histologically. At 30 days, minimal bone ingrowth was observed in untreated calvarial defects or in those that were treated with PLA plates alone. Defects treated with the cement alone demonstrated a modest amount of new woven bone deposition, primarily at the periphery of the implants. Defects treated with calcium phosphate cement over PLA mesh underlays were characterized by remodeling and woven bone deposition at 30 days, with complete or near-complete osseous bridging of the ectocranial implant surfaces. Progressive bone ingrowth was noted in all defects at 180 days, with near-complete replacement of all Norian CRS implants by host bone. The PLA mesh remained incompletely resorbed at 180 days. No inflammatory response to the implants was observed at either time point. Calcium phosphate cement may be safely used for craniofacial reconstruction in the presence of PLA implants without compromise to its biocompatibility, osteoconductivity, or remodeling capacity.

Surgical airway management in Pierre Robin sequence: is there a role for tongue-lip adhesion?

OBJECTIVE: The purpose of this study was to examine the efficacy of tongue-lip adhesion (TLA) in the management of clinically significant airway obstruction associated with Pierre Robin sequence. DESIGN: The records of all children admitted to The Children's Hospital of Philadelphia with a diagnosis of Pierre Robin sequence were reviewed. Charts were reviewed for birth data, diagnosis, preoperative airway management methods, and surgical intervention. Records of infants undergoing TLA were analyzed for timing of surgery, operative technique, postoperative complications, length of hospital stay, and treatment outcome. RESULTS: Over the 28-year period 1971 to 1999, 107 patients (47 boys, 60 girls) meeting the criteria for Pierre Robin sequence were admitted for treatment. Of these, 74 (69.2%) were successfully managed by positioning alone. Surgical management of the airway was performed in the remaining 33 (30.8%) patients, 29 of whom underwent TLA and 4 of whom underwent tracheostomy. Dehiscence of the adhesion occurred in five patients (17.2%), two of whom subsequently required tracheostomy. Within the group of patients who underwent mucosal adhesion alone, the dehiscence rate was 41.6%. When the adhesion included muscular sutures, however, dehiscence was not observed in any patient. Of the 24 patients in whom primary TLA healed uneventfully, airway obstruction was successfully relieved in 20 (83.3%). Failure of a healed TLA to relieve the airway obstruction resulted in conversion to a tracheostomy in four patients. Six patients who underwent TLA (20.7%) ultimately required a tracheostomy; five of these patients (83.3%) were syndromic. Of patients requiring preoperative intubation, 42.9% ultimately required tracheostomy. CONCLUSION: TLA successfully relieves airway obstruction that is unresponsive to positioning alone in the majority of patients with Pierre Robin sequence and should therefore play an important role in the management of these infants.

Repair of the immature craniofacial skeleton with a calcium phosphate cement: quantitative assessment of craniofacial growth.

The potential for growth restriction has limited the use of alloplastic materials for reconstruction of the growing craniofacial skeleton. A calcium phosphate cement that has been introduced recently for craniofacial reconstruction crystallizes in situ into a substance that resembles more closely the mineral phase of bone, thereby offering the potential for enhanced bioresorption and osteoconductivity. The purpose of these experiments was to assess quantitatively craniofacial growth after reconstruction of frontal craniectomy defects in skeletally immature animals with this calcium phosphate bone mineral substitute. To simulate the calvarial defects that result from unilateral fronto-orbital advancement procedures, unilateral frontal bone flaps were removed in 3-week-old female Yorkshire piglets. The bone flaps were trimmed medially and posteriorly, and were then reattached to the supraorbital ridge. The resulting 5-mm gap between the frontal bone flap and the native bone was either filled with Norian CRS bone cement (N = 3) or left empty (N = 3). After 90 days, the animals were killed and the skulls were harvested and cleared. Direct craniometric measurements were performed on the prepared dry skulls to assess craniofacial growth in all dimensions. Extensive remodeling was observed within defects treated with the calcium phosphate cement, with complete or near-complete replacement of the cement by host bone, resulting in a solid bony union. Direct craniometric measurements revealed no differences in craniofacial growth in any dimension between the operated and unoperated sides of the cranium in either group. These studies demonstrate that craniofacial growth is not restricted after reconstruction of frontal craniectomy defects with carbonated calcium phosphate cement in skeletally immature animals. The remodeling capacity of this material offers promise for its safe use in reconstruction of the growing calvarium.