Impact of Neighborhood Deprivation and Social Vulnerability on Outcomes and Interventions in Patients with Cleft Palate.

OBJECTIVE: To examine whether neighborhood disadvantage impacts length of follow-up, interventions, and outcomes for patients with cleft palate. DESIGN: Retrospective cohort. SETTING: Cleft Palate Craniofacial Institute Database at St. Louis Children's Hospital. PATIENTS/PARTICIPANTS: Patients with cleft palate following in St. Louis Children's Hospital Cleft Palate Multidisciplinary Team Clinic. INTERVENTIONS: Primary palatoplasty between 2012-2017. Patients were divided into quartiles across area deprivation index (ADI) and social vulnerability index (SVI), two validated, composite metrics of neighborhood disadvantage, to examine whether living in neighborhoods from different deprivation quartiles impacts outcomes of interest. MAIN OUTCOME MEASURE: Follow-up through age 5, surgeries and surgical complications, speech, developmental, and behavioral outcomes. RESULTS: 205 patients were included. 39% of patients belonged to the most deprived ADI quartile, while 15% belonged to the most vulnerable SVI quartile. There were no differences between ADI or SVI quartiles in number of operations received (p ≥ 0.40). Patients in the most deprived ADI quartile were significantly more likely to have speech/language concerns (OR 2.32, 95% CI [1.20-4.89], p = 0.01). Being in a more vulnerable SVI quartile was associated with developmental delay (OR 2.29, 95% CI [1.04-5.15], p = 0.04). ADI and SVI quartile did not impact risk of loss to follow-up in the isolated and combined cleft lip and palate subgroups (p ≥ 0.21). CONCLUSIONS: Neighborhood disadvantage impacts speech and developmental outcomes in patients with cleft palate despite comparable length of follow-up in multidisciplinary team clinic.

Multidisciplinary Optimal Outcomes Reporting and Team Clinic Retention in Isolated Nonsyndromic Cleft Palate.

OBJECTIVE: Optimal Outcomes Reporting was recently introduced to categorize outcomes after cleft palate repair. We seek to propose an expanded version of Optimal Outcomes Reporting and to determine if correlation exists between the expanded outcomes and persistence with team care follow-up through age 9. DESIGN: Retrospective cohort study. SETTING: Cleft team at large pediatric hospital. PATIENTS: Patients with isolated nonsyndromic cleft palate (n = 83) born from 2001-2012. MAIN OUTCOME MEASURES: Patients who continued to present at age 5 or greater were assessed for optimal outcomes. Optimal outcomes were: surgery - no fistula or velopharyngeal insufficiency; otolaryngology - no obstructive sleep apnea or signs of chronic middle ear disease; audiology - no hearing loss; speech-language pathology - no assessed need for speech therapy. RESULTS: Of the 83 patients identified, 41 were assessed for optimal outcomes. Optimal outcome in any discipline was not associated with follow-up through age 9 (0.112 ≤ p ≤ 0.999). For all disciplines, the group with suboptimal outcomes had a higher proportion of patients from geographic areas in the most disadvantaged quartile of social vulnerability index, with the strongest association in the group with suboptimal speech outcome (OR 6.75, 95% CI 0.841-81.1). CONCLUSIONS: Optimal outcomes and retention in team clinic were not statistically significantly associated, but clinically relevant associations were found between patients in the most disadvantaged quartile of social vulnerability and their outcomes. A patient-centered approach, including caregiver education about long-term care for patients with cleft palate, would allow for enhanced resource utilization to improve retention for patients of concern.

Surgical outcome and treatment trends in 1289 infants with micrognathia: a multicenter cohort.

BACKGROUND: Studies of infants with micrognathia, especially Robin Sequence (RS), are limited by its rarity and both phenotypic and diagnostic variability. Most knowledge of this condition is sourced from small, single-institution samples. METHODS: This is a cross-sectional study including infants with micrognathia admitted to 38 Children's Hospital Neonatal Consortium centers from 2010-2020. Predictor variables included demographic data, birth characteristics, cleft and syndrome status. Outcome variables included length of stay (LOS), death, feeding or respiratory support, and secondary airway operations. RESULTS: 1289 infants with micrognathia had a surgery to correct upper airway obstruction. Mean age and weight at operation were 34.8±1.8 weeks and 3515.4±42 grams, respectively. A syndromic diagnosis was made in 150 (11.6%) patients, with Stickler (5.4%) and Treacher Collins Syndromes (2.2%) most common. Operations included: mandibular distraction osteogenesis (MDO), 66.3%; tracheostomy, 25.4%; and tongue-lip adhesion (TLA), 8.3%. Tracheostomy patients had a lower birth weight, head circumference, gestational age, and APGAR scores. MDO patients were less likely to need a second airway operation compared to TLA patients (3.5%vs17.8%,p<0.001). The proportion of infants feeding exclusively orally at hospital discharge differed significantly, from most to least: MDO, TLA, tracheostomy. Hospital LOS was not statistically different for patients that had MDO and TLA, but was longer for those with primary tracheostomy. Mortality was low for all operations (0.5%). CONCLUSION: In this 1289 surgical patient cohort, MDO was associated with shorter hospital stay, improved oral feeding, and lower rates of secondary airway operations. Prospective multi-center studies are necessary to support these conclusions.

Advances in the Diagnosis and Treatment of Primary Ciliary Dyskinesia: A Review.

IMPORTANCE: Primary ciliary dyskinesia (PCD) is a rare, inherited condition involving motile cilia that line the upper and lower respiratory tracts, leading to chronic infections of the paranasal sinuses, middle ear, and bronchi that begin during infancy. Unfortunately, despite its early presentation, PCD is often recognized late. OBSERVATIONS: People with PCD have diverse clinical manifestations, including chronic upper and lower respiratory tract disease, laterality defects, and subfertility. Through efforts of multinational clinical collaboratives, 4 cardinal features have been described that identify people who likely have PCD: unexplained neonatal respiratory distress, left-right laterality defects, daily wet cough, and nonseasonal rhinosinusitis beginning before 6 months of age. Recent advances in the understanding of the genetics and pathogenesis of the disease have led to a revolution in the approach to screening and diagnostic testing. Moreover, PCD has a broad clinical spectrum, and genotype-phenotype associations are beginning to be recognized. CONCLUSIONS AND RELEVANCE: A high index of suspicion remains critical in diagnosing PCD. Children who have at least 2 of the major clinical features should be considered for further evaluation. Nevertheless, while newer tools have improved diagnostic capabilities, there is no single test that will diagnose every person with the disease. In people suspected of having PCD, nasal nitric oxide measurement is a useful screen, followed by diagnostic genetic testing and if negative, ciliary ultrastructural analysis. Despite otolaryngologic manifestations being common in infancy and persisting into adulthood, they have been understudied. Indeed, there are few randomized clinical trials examining the medicosurgical approaches to respiratory disease.

Evaluation of Discipline-Specific Outcomes Through a Multidisciplinary Team Clinic for Patients With Isolated Cleft Palate.

OBJECTIVE: To describe the incidence and timing of provider-specific interventions for children with isolated cleft palate. DESIGN: This was a retrospective cohort study involving review of medical records. SETTING: Multidisciplinary team care clinic at a tertiary academic children's hospital between January 2000 and July 2019. PATIENTS: Patients with isolated nonsyndromic cleft palate seen by an American Cleft Palate-Craniofacial Association-approved team; 138 children were included. MAIN OUTCOME MEASURES: Study outcomes included incidence of secondary velopharyngeal management, tympanostomy tube insertion, speech therapy, hearing loss, dental/orthodontic treatment, and psychology interventions. Provider-specific outcomes were calculated for patients at ages 0 to 3, 3 to 5, and >5 years. RESULTS: Median follow-up time was 7.0 years (interquartile range: 3.3-11.8 years). At their last team assessment, 42% of patients still had conductive hearing loss. The rate of tympanostomy tube insertions not done alongside a palatoplasty was highest for ages 3 to 5 and dropped after new American Academy of Otolaryngology-Head and Neck Surgery Foundation guidelines in 2013 (P = .015); 54% of patients received speech-language therapy during follow-up. Palatoplasty, psychology, and dental/orthodontic treatment were all less common than speech or ENT treatment (P < .01). Secondary palatoplasty was performed in 31 patients (22%). Patients who received speech, dental/orthodontic, or psychology intervention followed up longer than those who did not (9.8 vs 2.1 years, P < .001). CONCLUSION: Half of the patients terminated team follow-up by age 7, suggesting that burden of care outweighed perceived benefits of continued follow-up for many families. These results can be used to adjust protocols for children with isolated cleft palate.

Implementation of a screening tool for primary ciliary dyskinesia (PCD) in a pediatric otolaryngology clinic.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disease arising from motile ciliary dysfunction and associated with recurrent and chronic upper and lower respiratory tract infections. Pediatric otolaryngologists may see these patients prior to the development of lung disease. Features of PCD may overlap with other suppurative respiratory diseases, creating diagnostic challenges. A simple screening tool would be beneficial to identify potential patients who have chronic upper respiratory tract disease requiring further specialist evaluation. OBJECTIVE: To test a simple screening tool consisting of four questions to detect PCD in children with chronic otitis media and chronic rhinosinusitis seen in a tertiary otolaryngology clinic. METHODS: A prospective, single site, observational study in a tertiary care pediatric otolaryngology clinic. Children aged 3-17 years diagnosed with chronic otitis media or rhinosinusitis with onset at less than 2 years of age were recruited. All study subjects had at least one of four key clinical features for PCD as determined by answers to screening questions, while control subjects had none. All participants completed a medical history questionnaire and nasal nitric oxide measurements. Those with reduced nasal nitric oxide levels were referred to our PCD center for further evaluation. RESULTS: A total of 153 patients were screened and 62 subjects were enrolled. Of those, 35 were enrolled as study subjects and 27 as matched controls. Study subjects had mean age of 7.5 years (3.2-16.5) with pre-screening diagnosis of chronic otitis media (n = 29) or chronic rhinosinusitis (n = 6). Control subjects (n = 27) had mean age 7.2 years (3.0-16.3) with pre-screening diagnosis of chronic otitis media (n = 25), and chronic rhinosinusitis (n = 2). There were no differences in subject demographics or mean nasal nitric oxide values between the two groups (179.8 vs 210.8 nl/min). Ten individuals had low nasal nitric oxide values, 7 of which were normal on repeat testing. Three subjects failed to return for follow up evaluations. Four referrals were made for further evaluation on the basis of clinical symptoms and nasal nitric oxide results. While no new cases of PCD were detected, a subject and his sibling with recurrent sinopulmonary infections were referred for immunologic evaluation. CONCLUSION: The use of standardized screening questions can be used in an otolaryngology clinic to identify patients who require further evaluation for PCD or primary immunodeficiency.

Evaluation of Multidisciplinary Team Clinic for Patients With Isolated Cleft Lip.

OBJECTIVE: To report the incidences of secondary lip and nose operations, otolaryngology procedures, speech-language therapy, neurodevelopmental concerns, and dental and orthodontic issues in children with isolated cleft lip to inform multidisciplinary cleft team protocols. SETTING: An American Cleft Palate-Craniofacial Association-approved team at a tertiary academic children's hospital. DESIGN: Retrospective cohort study of patients evaluated through longitudinal clinic visits by a multidisciplinary cleft palate and craniofacial team between January 2000 and June 2018. PATIENTS, PARTICIPANTS: Children with nonsyndromic cleft lip with or without cleft alveolus (n = 92). RESULTS: Median age at final team visit was 4.9 years (interquartile range: 2.4-8.2 years). Secondary plastic surgery procedures were most common between ages 3 and 5 (135 per 1000 person-years), and the majority of these procedures were minor lip revisions. The rate of tympanostomy tube insertion was highest before age 3 (122 per 1000 person-years). By their final team visit, 88% of patients had normal hearing and 11% had only slight to mild conductive hearing loss. No patients had speech errors attributable to lip abnormalities. Psychological interventions, learning disabilities, and dental or orthodontic concerns were uncommon. CONCLUSIONS: Most patients with isolated cleft lip may not require long-term, longitudinal evaluation by cleft team specialists. Cleft teams should develop limited follow-up protocols for these children to improve resource allocation and promote value-based care in this patient population.

Prevalence of Semicircular Canal Hypoplasia in Patients With CHARGE Syndrome: 3C Syndrome.

Importance: CHARGE syndrome refers to a syndrome involving coloboma, heart defects, atresia choanae, retardation of growth and development, genitourinary disorders, and ear anomalies. However, Verloes revised the characteristics of CHARGE syndrome in 2005 to define this syndrome more broadly. Deficiency of the semicircular canals is now a major criterion for CHARGE syndrome. Objective: To characterize patients with CHARGE syndrome at our center using Verloes' criteria and to reevaluate the nomenclature for this condition. Design, Setting, and Participants: We performed a medical chart review of patients with CHARGE syndrome and reviewed their temporal bone imaging studies at a tertiary care children's hospital affiliated with Washington University in St Louis. Two authors independently reviewed each imaging study (A.W. and K.H.). Radiologic studies, physical findings, genetic tests, and other diagnostic tests were included. Patients with no temporal bone imaging studies were excluded. Results: Eighteen children were included in this study; 13 children (72%) were male, and the mean (median; range) age of patients at the time of inner ear imaging studies was 2 years (4.5 years; 8 months to 8 years). Coloboma was present in 13 patients (72%) and choanal atresia in 5 (28%); semicircular canal anomalies were present in all patients. Additionally, 13 patients (72%) were diagnosed as having hindbrain anomalies, 17 (94%) as having endocrine disorders, 17 (94%) as having mediastinal organ malformations, and all as having middle or external ear abnormalities and development delay. Cleft lip and cleft palate were found in 6 of 14 patients (43%) who did not have choanal atresia. We tested 16 patients for mutations in the CHD7 gene; 10 were positive (63%) for mutations, 4 (25%) were negative, and 2 (13%) were inconclusive. Conclusions and Relevance: Semicircular canal anomalies were the most consistent finding in our patients with CHARGE syndrome. Given the high prevalence of semicircular canal hypoplasia and importance of imaging for diagnosing CHARGE syndrome, we propose changing the term CHARGE syndrome to 3C syndrome to emphasize the importance of the semicircular canals and to recall the 3 major criteria for diagnosis: coloboma, choanal atresia, and semicircular canal anomaly. The nomenclature would also reference the 3 semicircular canals in each ear. This new name for CHARGE syndrome would provide a mnemonic and focus the disease on the most important clinical criteria for diagnosis.

Primary surgery vs primary sclerotherapy for head and neck lymphatic malformations.

IMPORTANCE: The optimal treatment for head and neck lymphatic malformations (LMs) is unknown. To our knowledge, this is the first head-to-head comparison of primary surgery and sclerotherapy for this condition. OBJECTIVE: To compare surgery and sclerotherapy as initial treatment for head and neck LMs. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study including patients in 2 pediatric vascular anomaly programs receiving treatment for head and neck LMs. INTERVENTIONS: Primary surgery or primary sclerotherapy and any subsequent therapy within 1 year. MAIN OUTCOMES AND MEASURES: Treatment effectiveness was measured by (1) need for further therapy after first treatment and within 1 year and (2) change in Cologne Disease Score (CDS). Resource utilization was reflected by total intervention number, hospital and intensive care unit (ICU) days, and tracheostomy placement. RESULTS: A total of 174 patients were studied. Their mean (SD) age at presentation was 4.2 (4.7) years; 45.1% were female. The initial treatment was surgery in 55.8%, sclerotherapy in 35.1%, and other interventions in 9.1%. The LM stage ranged from 1 to 5, with similar distributions (P = .15) across initial treatment types; 31.2% of LMs were macrocystic, 34.8% were microcystic, and 33.9% were mixed, with similar distributions across treatment types. Patients receiving sclerotherapy had worse pretreatment CDS subscores for respiration, nutrition, and speech (all P ≤ .02). In univariate analysis, initial surgery and initial sclerotherapy had similar effectiveness after the first intervention (P = .21) and at 1 year (P = .30). In multivariate analysis controlling for lesion stage and type, initial surgery and sclerotherapy did not differ in effectiveness after the first intervention (P = .28) or at 1 year (P = .97). Total CDS and subscale changes were similar between treatment types except for the nutrition subscale. Treatment type did not predict total number of interventions (P = .64), total hospital days (P = .34), total ICU days (P = .59), or higher likelihood of subsequent tracheostomy (P = .36). Higher LM stage predicted more hospital and ICU days and higher likelihood of tracheostomy (all P ≤ .02). CONCLUSIONS AND RELEVANCE: In this multisite comparison, initial surgery and sclerotherapy for head and neck LMs were similar in effectiveness and resource utilization. Higher stage predicted greater resource utilization.

Status of propranolol for treatment of infantile hemangioma and description of a randomized clinical trial.

OBJECTIVES: Our primary objective was to review the current use of propranolol for treatment of infantile hemangioma (IH), specifically regarding 1) the age at initiation of therapy, 2) the method of initiation, 3) the use of other adjuvant therapy, 4) the duration of therapy and relapse rate, 5) the adverse events, and 6) the outcome. Our secondary objective was to describe a randomized, controlled, single-blinded trial comparing propranolol to prednisolone for treatment of IH. METHODS: Ovid Medline and PubMed searches were completed for the MeSH keywords "propranolol" and "hemangioma." Forty-nine English-language articles were published between June 2008 and September 2010, and 28 of these reported data from a total of 213 patients. Only 6 studies treated more than 10 patients, and these were selected for review in detail (154 patients). RESULTS: The treatment was initiated during infancy in 92.9% of patients (mean, 4.5 months). Sixty-five percent of patients were treated with 2 mg/kg per day, and 25.3% with 3 mg/kg per day. Patients were monitored overnight at initiation of treatment in 3 series (59 patients), for 4 to 6 hours as outpatients in 2 series (62 patients), and initially as inpatients but later as outpatients in 1 series (32 patients). Propranolol was used as sole therapy in about two thirds of patients (103 patients). Treatment was ongoing in 46% of patients at the time of publication. The average treatment duration in the remaining patients was 5.1 months. Rebound growth occurred in 21% of patients after a mean of 4.3 months of therapy. Adverse events occurred in 18.1% of patients and included hypotension in 6, somnolence in 6, wheezing in 4, insomnia, agitation, and/or nightmares in 6, cool hands or night sweats in 2, gastroesophageal reflux in 3, and psoriasis-like rash in 1. All authors reported a favorable outcome with propranolol, but the definition of efficacy was not standardized. CONCLUSIONS: Propranolol is an attractive alternative to other treatments for IH. Despite apparent widespread use of this medication, the data are limited, and prospective studies are lacking for this indication. The relatively high rate of adverse effects supports the need for careful monitoring of patients on this therapy. Fastidious reporting of adverse events and objective evaluation of early and late outcomes are necessary to improve our understanding of the use of propranolol for this indication.

Branchio-oto-renal syndrome: the mutation spectrum in EYA1 and its phenotypic consequences.

EYA1 mutations cause branchio-oto-renal (BOR) syndrome. These mutations include single nucleotide transitions and transversions, small duplications and deletions, and complex genomic rearrangements. The last cannot be detected by coding sequence analysis of EYA1. We sought to refine the clinical diagnosis of BOR syndrome by analyzing phenotypic data from families segregating EYA1 disease-causing mutations. Based on genotype-phenotype analyses, we propose new criteria for the clinical diagnosis of BOR syndrome. We found that in approximately 40% of persons meeting our criteria, EYA1 mutations were identified. Of these mutations, 80% were coding sequence variants identified by SSCP, and 20% were complex genomic rearrangements identified by a semiquantitative PCR-based screen. We conclude that genetic testing of EYA1 should include analysis of the coding sequence and a screen for complex rearrangements.