Effect of Speaking Valves on Tracheostomy Decannulation.

Introduction Despite several pediatric tracheostomy decannulation protocols there remains tremendous variability in practice. The effect of tracheostomy capping on decannulation has been studied but the role of speaking valves (SVs) is unknown. Objective Given the positive benefits SVs have on rehabilitation, we hypothesized that SVs would decrease time to tracheostomy decannulation. The purpose of the present study was to evaluate this in a subset of patients with chronic lung disease of prematurity (CLD). Methods A retrospective chart review was performed at a tertiary care children's hospital. A total of 105 patients with tracheostomies and CLD were identified. Data collected included demographics, gestational age, congenital cardiac disease, airway surgeries, granulation tissue excisions, SV and capping trials, tracheitis episodes, and clinic visits. Statistics were performed with logistic and linear regression. Results A total of 75 patients were included. The mean gestational age was 27 weeks (standard deviation [SD] = 3.6) and the average birthweight was 1.1 kg (SD = 0.6). The average age at tracheostomy was 122 days (SD = 63). A total of 70.7% of the patients underwent decannulation and the mean time to decannulation (TTD) was 37 months (SD = 19). A total of 77.3% of the patients had SVs. Those with an SV had a longer TTD compared to those without (52 versus 35 months; p = 0.008). Decannulation was increased by 2 months for every increase in the number of hospital presentations for tracheitis ( p = 0.011). Conclusion The present study is the first, to our knowledge, to assess the effect of SVs on tracheostomy decannulation in patients with CLD showing a longer TTD when SVs are used.

Use of botox for sialorrhea and dysphagia in the neonatal population.

INTRODUCTION: Botox is frequently used for sialorrhea in patients with compromised airways and those with etiologies causing difficulty with secretion management (i.e. strokes, neurologic disorders, etc.). There are no published studies regarding the use of botulinum toxin (BoNT) in the neonate population. We aim to discuss our experience and safety of BoNT use in the neonate population in regards to alleviating secretion management and airway protection. METHODS: Retrospective review of neonates admitted to the neonatal intensive care unit (NICU) ≤12 months of age who received BoNT injection to submandibular (SMG) and parotid (PG) glands for sialorrhea/dysphagia. BoNT was administered under ultrasound (u/s) guidance by interventional radiology. RESULTS: 6 children were examined. 2 (33 %) were male. Avg NICU stay was 87.5 ± 33.1 days. 2 underwent surgical airway intervention prior to injection. Mean age at initial BoNT was 1.5 ± 0.7 months. Avg weight at injection was 4 ± 1.1 kg. Each PG and SMG were injected in 5/6 cases. Bilateral SMG were unidentified on u/s in 1 case and thus not injected. Dose range injected per gland was 5-15u. 100 % required tube feeds, 50 % with tubes distal to stomach (NJT/NDT). 83 % were completely NPO prior to injection and there was no noted clinical improvement in oral skills post injection. All had noted desats/apneas prior to injection and 83 % had reported decreased events post injection. 50 % had reported decrease O2 requirements and frequent suctioning 2wks after injection, however 2 (33 %) required surgical airway intervention after injection (trach, SGP/MDO). 4/6 (67 %) trialed medical therapy, anticholinergics being the most common. 50 % underwent 2nd injection (age = 6.5 ± 0.3 months) avg. 4.7 ± 0.7mo after 1st injection, and the same 3pts underwent 3rd injection (age = 12.5 ± 2.4 months) avg. 6.1 ± 2.5mo after 2nd injection. 1 pt. had a total 6 injections. There were no injection related complications. CONCLUSION: BoNT injection is a safe, non-invasive alterative for management of sialorrhea in neonates. Further extensive study needs to be performed to identify the optimal dose per gland in this population.

Pediatric Tracheostomy Safety: Implementation of an Airway Safety Placard.

BACKGROUND: First health care professionals arriving at the bedside in tracheostomy-related emergencies are rarely the surgical subspecialists who placed the tracheostomy and are unfamiliar with the relevant anatomy and tracheostomy specifications for the individual patient. We hypothesized that implementing a bedside airway safety placard would increase caregiver confidence, understanding of airway anatomy, and management of patients with a tracheostomy. METHODS: A prospective survey study was performed by distributing a tracheostomy airway safety survey before and after implementation of an airway safety placard in a 6-month study period. Placards emphasizing critical airway anomalies as well as emergency management algorithm suggestions designed by the otolaryngology team at the time of tracheostomy were placed at the head of the bed and traveled with the patient during transport around the hospital. RESULTS: Of 377 staff members requested to complete the surveys, 165 (43.8%) responses were obtained, and 31 (8.2% [95% CI 5.7-11.5]) paired pre- and post-implementation responses were recorded. Differences were found in the paired responses, including increases in the domains of confidence (P = .009) and experience (P = .01) post implementation. Less experienced providers (≤ 5 y of experience) (P = .005) and providers from neonatology (P = .049) demonstrated improved confidence post implementation, which was not observed in their more experienced (> 5 y) or respiratory therapy counterparts. CONCLUSIONS: Given the limitations of a low survey response rate, our findings suggest that an educational airway safety placard initiative can be a simple, feasible, and low-cost quality improvement tool to enhance airway safety and possibly decrease potentially life-threating complications among pediatric patients with a tracheostomy. The implementation of the tracheostomy airway safety survey at our single institution warrants a larger multi-center study and validation of the survey.

Prevalence and Management of Laryngomalacia in Patients With Pierre Robin Sequence.

OBJECTIVE: To characterize the prevalence and presentation of laryngomalacia and efficacy of supraglottoplasty (SGP) in a cohort of patients with Pierre Robin Sequence (PRS). DESIGN: Retrospective cohort study. SETTING: Tertiary-care children's hospital. PATIENTS, PARTICIPANTS: Consecutive patients with PRS born between January 2010 and June 2018. MAIN OUTCOME MEASURES: Chart review included demographics, comorbid airway obstruction including laryngomalacia, timing of surgical interventions, clinical symptoms, sleep study data, and modified barium swallow study data.126 patients with PRS were included; 54% had an associated syndrome, 64% had an overt cleft palate, and 22% had a submucous cleft palate. 64/126 were noted to have laryngomalacia (51%). Patients with concurrent PRS and laryngomalacia were significantly more likely to have submucous cleft palate (P = .005) and present with aspiration with cough (P = .01) compared to patients with PRS without laryngomalacia. Patients with concurrent laryngomalacia and PRS showed a significant decrease in apnea-hypopnea index (AHI) and obstructive AHI (OAHI) after mandibular distraction, with a median AHI and OAHI improvement of 22.3 (P = .001) and 19.8 (P = .002), respectively. Patients who underwent only SGP did not show significant improvement in these parameters (P = .112 for AHI, P = .064 for OAHI).The prevalence of laryngomalacia in our PRS cohort was 51%. Patients with PRS and laryngomalacia are more likely to present with overt aspiration compared to patients with PRS without laryngomalacia. These data support that laryngomalacia does not appear to be a contraindication to pursuing MDO.

Initiation of acid suppression therapy for laryngomalacia.

OBJECTIVE: Evidence supporting the use of acid suppression therapy (AST) for laryngomalacia (LM) is limited. The objective of this study was to determine if outpatient-initiated AST for LM was associated with symptom improvement, weight gain, and/or avoidance of surgery. METHODS: A retrospective cohort was reviewed at a tertiary-care children's hospital. Patients were included if they were diagnosed with LM at ≤6 months of age, seen in an outpatient otolaryngology clinic between 2012 and 2018, and started on AST. Primary outcomes were improvement of airway and dysphagia symptoms, weight gain, and need for surgery. Severity was assessed by symptom severity. RESULTS: Of 2693 patients reviewed, 199 met inclusion criteria. Median age of diagnosis was 4 weeks (range: 0-29 weeks). LM was classified as mild/moderate (71.4%) and severe (28.6%) based on symptom severity. Severity on flexible fiberoptic laryngoscopy (FFL) was not associated with clinical severity. Weight percentile, airway symptoms, and dysphagia symptoms improved within the cohort. In total, 26.1% underwent supraglottoplasty (SGP). In multivariate analysis, only severe LM on FFL was predictive of SGP (OR: 7.28, 95%CI: 1.91-27.67, p = .004). CONCLUSION: Clinical symptom severity did not predict response to AST raising the question of utility of AST in LM. Severity of LM based on FFL, not clinical severity, was associated with decision to pursue SGP. Prospective randomized trials are needed to better understand the role of AST in LM. LEVEL OF EVIDENCE: Level 3.

Dysphagia in Pediatric Patients with Tracheostomy.

OBJECTIVE: Post-tracheotomy swallowing function has not been well described in the pediatric population. This study aims to (1) determine differences in swallowing functioning pre- and post-tracheotomy and (2) examine the association between postoperative dysphagia and indication for tracheotomy, age at the time of tracheotomy, and time between tracheotomy and modified barium swallow (MBS). METHODS: A retrospective chart review was performed on 752 patients who underwent a tracheotomy from 2003 to 2018 and had adequate documentation for review. Patients were included if they received a post-operative MBS. Descriptive statistics, logistic regression, and Fisher's exact test were used to analyze the data. RESULTS: The cohort included 233 patients. The mean age at the time of tracheotomy was 25 months (±50.5). The indications for the tracheotomy were upper airway obstruction (110/233, 47.2%), chronic respiratory failure (104/233, 44.6%), and neurologic disease (19/233, 8.2%). The mean time from tracheotomy to post-operative MBS was 224 days (±297.7). Of the patients who had documented pre- and post-tracheotomy diets, nearly half of patients had improvement in their swallowing function after tracheotomy placement (82/195; 42.1%). Post-tracheotomy MBS recommended thickened liquids in 30.9% of the patients (72/233) and 42.5% (99/233) were recommended thin liquids. The remainder (62/233, 26.6%) remained nothing by mouth (NPO). Patients with neurological disease as the indication for the tracheotomy were more likely to remain NPO (P = .039). CONCLUSION: A tracheotomy can functionally and anatomically affect swallowing in pediatric patients. The majority of our studied cohort was able to resume some form of an oral diet postoperatively based on MBS. This study highlights the need for objective measurements of swallowing in the postoperative tracheotomy patient to allow for safe and timely commencement of an oral diet. LEVEL OF EVIDENCE: Level 3.

Primary versus secondary closure of tracheocutaneous fistula in pediatric patients.

OBJECTIVE: Up to 50% of pediatric patients have a persistent tracheocutaneous fistula (TCF) after tracheostomy decannulation. Classically these fistula tracts were excised and completely closed in a multilayered fashion, but recently closure by secondary intention has become the standard of care. However, variations in postoperative care still exist. The primary objectives of this study were to compare outcomes between patients who had a primary closure versus closure by secondary intention after excision of a TCF in children with a tracheostomy placement at one year old or less and to determine if closure by secondary intention will be equally efficacious compared to traditional primary closure. METHODS: Patients ages 0-21 years who had a primary or secondary closure of a TCF at a tertiary care children's hospital following decannulation of a tracheostomy tube were reviewed and those with a tracheostomy placement ≤1 year old were included. Demographic information, comorbidities, and surgical information were extracted from inpatient and outpatient charts. Mann-Whitney U test, Fisher's Exact test, and logistic regression to compare outcomes across the two TCF surgical groups. RESULTS: A total of 64 patients met inclusion with primary closures in 25 (39.1%) patients and secondary closures in 39(60.9%) patients. Patients who underwent secondary closure had a significantly shorter surgery duration (p < .001), shorter ICU length of stay (p < .001), and shorter postop LOS (p < .001). There were no differences in cardiac complications, respiratory complications, and the need for additional closure surgery between the two techniques, p > .05. Time from decannulation to TCF in months increased with primary closure, p = .010. CONCLUSION: Closure of tracheocutaneous fistula by secondary intention is safe and effective and can allow for shorter hospital stays in children with a tracheostomy placement at a year old or less.

Readmissions and mortality in pediatric tracheostomy patients: Are we doing enough?

OBJECTIVES: Pediatric patients who undergo tracheostomy tube placement are medically complex with a high risk of morbidity and mortality. They are often premature with multiple cardiopulmonary comorbidities. This study reviews the demographics and outcomes within this population to identify at-risk patient groups at our hospital. METHODS: A retrospective chart review of those with pediatric tracheostomy placement from 2015 to 2016 at our hospital was performed (n = 92). Demographic and post-discharge data were collected at 30, 60, and 90-days during the global period. RESULTS: Ventilator dependence was the most common reason for placement. 79.3% of patients had two or more major comorbidities. 44% had an emergency department (ED) visit and subsequent hospital admission within the first 90 days post-discharge, with 36% being trach/respiratory-related. The 90-day mortality was 19.6%; however, at the time of chart review, mortality was 35% with only 1 (1.1%) being from trach-related complications. Patients with longer admissions were more likely to die prior to discharge, p = .001. Lastly, patients who died were 3 times more likely to have > 25% no-shows to their outpatient appointments compared to those living throughout the study period. CONCLUSION: Our population had a high incidence of ED visits, readmission rates, and mortality; however, trach-related causes remained low. Mortality risk increased with more no-show appointments and residing a further distance from our hospital. Furthermore, multiple co-morbidities, with longer hospital stays also increased risk of mortality. Identifying those with the highest risk for complications will enable us to target families for increased home-care education to decrease readmissions and mortality. LEVEL OF EVIDENCE: 4.

Pediatric subperiosteal orbital abscess characterization and prediction of size, location, and management.

INTRODUCTION: Subperiosteal orbital abscess (SPOA) is a serious suppurative complication of pediatric sinusitis. The objective of this study is to stratify patient selection into those best treated medically versus surgically based on clinical outcomes. METHODS: This is a retrospective review of patients diagnosed with SPOA complicating sinusitis treated at a tertiary care pediatric hospital from 2002 through 2016. SPOA was diagnosed by CT scan. Characteristics evaluated include demographics, abscess size, location, and measurements, length of hospital stay, medical and surgical interventions, presenting symptoms, and complications. RESULTS: A total of 108 total SPOA secondary to sinusitis patients were included. A majority, 72.2%, were male with an average age at presentation of 6.8 years. The mean ± standard deviation abscess cubic volume was 0.98 ± 1.27 cm3 (median(range) = 0.44(0.01-7.34 cmcm3)). With an abscess volume of 0.510 cm3, there was a sensitivity of 71.2% and a specificity of 84.4% for needing surgical drainage. Those with large abscesses at our volume threshold were 13 times more likely to require surgery than those with small abscesses, OR: 13.41, 95%CI: 5.02-35.86, p < .001. Patients that required surgery had an abscess closer to the orbital apex with the majority, 25 (61.0%), being the most proximal to the apex, p = .004. The likelihood of surgery decreased with increased distance from the orbital apex in medial abscesses (OR:.92, 95%CI: 0.86-0.98, p = .009). CONCLUSION: In the pediatric population, SPOA is a serious consequence of sinusitis. This study provides evidence supporting that larger abscess size is a significant risk factor for requiring surgery. The appeal of our study is that it provides evidence and support that employ clinical parameters already assessed as standard practice in evaluating these patients. In summarizing the clinical translational relevance of our study, when determining whether to treat a patient with surgery and antimicrobial/medical therapy vs. non-surgical medical therapy alone, the clinician should focus on size of 0.510 cm3 or larger for abscesses in any location as a relative indication for surgery.

Predictive Utility of the Penetration-Aspiration Scale in Inter-Arytenoid Injection Augmentation.

OBJECTIVES/HYPOTHESIS: To determine the utility of preoperative penetration-aspiration scale (PAS) scores and clinical findings on modified barium swallow (MBS) in predicting advancement of diet after interarytenoid injection augmentation (IAIA). STUDY DESIGN: Retrospective review. METHODS: In this retrospective cohort study, 372 consecutive patients who underwent IAIA for pharyngeal dysphagia between 2009 and 2019 were initially identified. Patients were excluded from the study if they had insufficient preop MBS, no postop MBS within 3 months of injection, supraglottoplasty, or underlying neurological condition. Ninety-three patients were included in the study. Pre- and postoperative PAS scores were recorded, as were pre and postop diets. PAS scores were calculated by a single pediatric speech and language pathologist. RESULTS: Average PAS score on MBS was 5.87 (standard deviation [SD] 2.74); median (range) = 8 (1-8). Postop average was 4.29 (SD 3.02); median (range) = 2 (1-8), P < .001. Those with worse preop PAS scores had increased odds of improvement in diet (odds ratio 1.24, 95% confidence interval [CI] 1.02-1.49, P = .029). An improvement in PAS score of 3.0 or greater predicted an improvement in diet with a sensitivity of 76.7% and a specificity of 85.7%. CONCLUSIONS: PAS score on MBS can be a useful tool when assessing pediatric patients who may be candidates for IAIA. Prospectively comparing PAS score in patients post-IAIA to patients solely undergoing diet modification can help to better objectively assess differences in outcomes and understand the full utility of PAS score. LEVEL OF EVIDENCE: Level III (Individual Cohort Study) Laryngoscope, 131:E1707-E1713, 2021.

Translatable mitochondria-targeted protection against programmed cardiovascular dysfunction.

The prenatal origins of heart disease in offspring have been established. However, research in species with developmental milestones comparable to humans is lacking, preventing translation of this knowledge to clinical contexts. Using sheep and chickens, two species with similar cardiovascular developmental milestones to humans, we combined in vivo experiments with in vitro studies at organ, cellular, mitochondrial, and molecular levels. We tested mitochondria-targeted antioxidant intervention with MitoQ against cardiovascular dysfunction programmed by developmental hypoxia, a common complication in human pregnancy. Experiments in sheep determined in vivo fetal and adult cardiovascular function through surgical techniques not possible in humans, while those in chicken embryos isolated effects independent of maternal or placental influences. We show that hypoxia generates mitochondria-derived oxidative stress during cardiovascular development, programming endothelial dysfunction and hypertension in adult offspring. MitoQ treatment during hypoxic development protects against this cardiovascular risk via enhanced nitric oxide signaling, offering a plausible intervention strategy.

Cost benefit of coblation versus electrocautery adenotonsillectomy for pediatric patients.

INTRODUCTION: Coblation and electrocautery are two common techniques used for adenotonsillectomy (T&A). Numerous studies have assessed surgical outcomes of coblation versus electrocautery and overall, postoperative complications are similar with the exception of a decrease in patient reported postoperative pain for coblation. Instrumentation required for coblation is significantly more expensive than that required for electrocautery. With minimal outcome differences, justification for the additional instrumentation costs is difficult. We performed this study to assess if there is a difference between operative & postoperative costs of electrocautery and coblation. METHODS: 300 patient medical records were reviewed from 2015 to 2017 with equal numbers of electrocautery and coblation surgeries. Outcome measures included finance information, duration and cost of OR and Phase I and Phase II post-anesthesia care unit (PACU), in-hospital pharmacy costs, and postoperative complications. Logistic regression was used for analysis. RESULTS: The median patient age for each surgical technique was 6 years old. Electrocautery resulted in more time in the OR compared to coblation, (OR:1.11,95%CI:1.07-1.15, p < .001), with greater associated costs, p < .001. Electrocautery patients were under anesthesia longer and had a longer surgical duration, p < .001. These same patients had longer duration in Phase II PACU, p = .028, and were given pain medications an increased number of times, p < .001. Total costs including operative expense, physician charges, OR and anesthesia times, pharmacy, and instrument were significantly higher for electrocautery patients, p = .003. There were no differences in ED visits, post-tonsillectomy bleed, or additional surgery between techniques, p > .05. CONCLUSION: T&A electrocautery technique was found to have increased overall indirect costs. Costs of instrumentation in addition to increased operative time, use of analgesics and post-operative care contribute to costs associated with electrocautery and coblation should be used when assessing surgical costs.

The Generalizability of the Clinical Assessment Score-15 for Pediatric Sleep-Disordered Breathing.

OBJECTIVE: The Clinical Assessment Score-15 (CAS-15) has been validated as an office-based assessment for pediatric sleep-disordered breathing in otherwise healthy children. Our objective was to determine the generalizability of the CAS-15 in a multi-institutional fashion. METHODS: Five hundred and thirty children from 13 sites with suspected sleep-disordered breathing were recruited, and the investigators completed the CAS-15. Based on decisions made in the course of clinical care, investigators recommended overnight polysomnography, observation, medical therapy, and/or surgery. Two hundred and forty-seven subjects had a follow-up CAS-15. RESULTS: Mean age was 5.1 (2.6) years; 54.2% were male; 39.1% were white; and 37.0% were African American. Initial mean (standard deviation [SD]) CAS-15 was 37.3 (12.7), n = 508. Spearman correlation between the initial CAS-15 and the initial apnea-hypopnea index (AHI) was 0.41 (95% confidence interval [CI], 0.29, 0.51), n = 212, P < .001. A receiver-operating characteristic curve predicting positive polysomnography (AHI > 2) had an area under the curve of 0.71 (95% CI, 0.63, 0.80). A score ≥ 32 had a sensitivity of 69.0% (95% CI, 61.7, 75.5), a specificity of 63.4% (95% CI, 47.9, 76.6), a positive predictive value of 88.7% (95% CI, 82.1, 93.1), and a negative predictive value of 32.9% (95% CI, 23.5, 44.0) in predicting positive polysomnography. Among children who underwent surgery, the mean change (SD) score was 30.5 (12.6), n = 201, t = 36.85, P < .001, effect size = 3.1. CONCLUSION: This study establishes the generalizability of the CAS-15 as a useful office tool for the evaluation of pediatric sleep-disordered breathing. LEVEL OF EVIDENCE: 2B Laryngoscope, 130:2256-2262, 2020.

Dynamic tonsillar prolapse masquerading as paradoxical vocal fold movement dysfunction.

INTRODUCTION: Paradoxical vocal fold movement dysfunction (PVFMD) is a disorder in which the vocal folds involuntarily adduct during inspiration resulting in stridor, cough, dysphonia and dyspnea. Diagnosis of PVFMD is difficult given the episodic nature of the disorder and the often-normal laryngeal exam in between episodes. Moreover, additional sources of obstruction have been identified as sources of Periodic Occurrence of Laryngeal Obstruction (POLO). Treatments can vary with site of obstruction. OBJECTIVE: To evaluate pediatric patients presenting to a Vocal Fold Dysfunction Center for evaluation of exertional, inspiratory, harsh breath sounds and dyspnea suggestive of PVFMD whom were found to have a dynamic obstruction of the upper airway due to adenotonsillar hypertrophy and prolapse. METHODS: Retrospective chart review of patients diagnosed with exertional dynamic tonsillar prolapse whom have undergone adenotonsillectomy. Clinical characteristics, spirometry, exam findings and response to adenotonsillectomy were recorded. RESULTS: Seven patients with exercise induced dyspnea and respiratory distress with whom underwent exercise spirometry then subsequent adenotonsillectomy were identified. Symptomatic co-morbidities were common and included: rhinitis (43%), reflux (29%), sleep disordered breathing (29%), asthma (14%), obesity (14%), prematurity (14%) and anxiety/post-traumatic stress disorder (PTSD) (14%). Preoperative use of bronchodilators or reflux medications was common. All patients were noted to have >50% oropharyngeal obstruction secondary to tonsillar hypertrophy and dynamic lateral pharyngeal collapse or tonsillar prolapse with inspiration. No exercise induced paradoxical vocal fold dysfunction was identified. All baseline and most exertion FVC, FEV1, FEV1/FVC and FEF 25-75% were normal. Four patients had flow volume loops suggestive of obstruction. All patients had symptomatic improvement after adenotonsillectomy. CONCLUSIONS: Dynamic tonsillar prolapse can result in subjective exertional dyspnea and objective upper airway resistance mimicking PVFMD and treatment with adenotonsillectomy can greatly reduce symptoms.

Outcomes and swallowing evaluations after injection laryngoplasty for type I laryngeal cleft: Does age matter?

OBJECTIVES: To improve the recognition of differences in presentation amongst patients with type 1 laryngeal clefts of various ages and better understand the age dependent outcomes of injection laryngoplasty. A second aim was to analyze the discrepancies between swallow assessment modalities in various age groups with type I laryngeal clefts undergoing injection laryngoplasty. METHODS: A retrospective review of electronic medical records of patients who underwent injection laryngoplasty from 2009 through 2015 at a tertiary care children's hospital. Data extracted included: Demographics, histories and physical exam findings, diagnostic studies, and medical and surgical treatments. RESULTS: Most (72/102, 70.6%) patients were male with a median gestational age at birth of 37 weeks (range 24-41 weeks). Formula thickening and GERD medications were used in 94/102 (92.2%) and 97/102 (95.1%) patients, respectively. Comorbid GERD, laryngomalacia, tracheomalacia, and subglottic stenosis were present in 98/102 (96.1%), 40/102 (39.2%), 9/102 (8.8%), and 14/102 (13.7%) patients, respectively. There was no significant difference in demographics, comorbidities or medical therapy between age groups. Symptoms at presentation differed between age groups with stridor (χ2(1) = 11.6, p = 0.002) and cyanosis (χ2(1) = 8.13, p = 0.012) being more common in the 0-3-month group compared to the 12-36 month group. Symptom resolution and the odds of undergoing additional surgery (second injection or suture repair) over time, however, did not differ. There was a significant reduction in aspiration with thins during FEES (McNemar χ2(1) = 10.7, p = 0.002) and aspiration with nectar during MBS (McNemar χ2(1) = 5.26, p = 0.035) post-injection. After injection, there was significant agreement in aspiration with thins between FEES and MBS (kappa = 0.308 ±â€¯SE 0.170, p = 0.035). However, finding aspiration with thins was more common during MBS than during FEES (McNemar χ2(1) = 7.00, p = 0.016). There were no differences in swallow evaluation findings between the age groups. CONCLUSIONS: Symptoms of type I laryngeal clefts may differ by age. However, there was no impact of age on the safety and efficacy of surgical intervention.

Altered autonomic control of heart rate variability in the chronically hypoxic fetus.

KEY POINTS: Fetal heart rate variability (FHRV) has long been recognised as a powerful predictor of fetal wellbeing, and a decrease in FHRV is associated with fetal compromise. However, the mechanisms by which FHRV is reduced in the chronically hypoxic fetus have yet to be established. The sympathetic and parasympathetic influences on heart rate mature at different rates throughout fetal life, and can be assessed by time domain and power spectral analysis of FHRV. In this study of chronically instrumented fetal sheep in late gestation, we analysed FHRV daily over a 16 day period towards term, and compared changes between fetuses of control and chronically hypoxic pregnancy. We show that FHRV in sheep is reduced by chronic hypoxia, predominantly due to dysregulation of the sympathetic control of the fetal heart rate. This presents a potential mechanism by which a reduction in indices of FHRV predicts fetuses at increased risk of neonatal morbidity and mortality in humans. Reduction in overall FHRV may therefore provide a biomarker that autonomic dysregulation of fetal heart rate control has taken place in a fetus where uteroplacental dysfunction is suspected. ABSTRACT: Although fetal heart rate variability (FHRV) has long been recognised as a powerful predictor of fetal wellbeing, the mechanisms by which it is reduced in the chronically hypoxic fetus have yet to be established. In particular, the physiological mechanism underlying the reduction of short term variation (STV) in fetal compromise remains unclear. In this study, we present a longitudinal study of the development of autonomic control of FHRV, assessed by indirect indices, time domain and power spectral analysis, in normoxic and chronically hypoxic, chronically catheterised, singleton fetal sheep over the last third of gestation. We used isobaric chambers able to maintain pregnant sheep for prolonged periods in hypoxic conditions (stable fetal femoral arterial PO2 10-12 mmHg), and a customised wireless data acquisition system to record beat-to-beat variation in the fetal heart rate. We determined in vivo longitudinal changes in overall FHRV and the sympathetic and parasympathetic contribution to FHRV in hypoxic (n = 6) and normoxic (n = 6) ovine fetuses with advancing gestational age. Normoxic fetuses show gestational age-related increases in overall indices of FHRV, and in the sympathetic nervous system contribution to FHRV (P < 0.001). Conversely, gestational age-related increases in overall FHRV were impaired by exposure to chronic hypoxia, and there was evidence of suppression of the sympathetic nervous system control of FHRV after 72 h of exposure to hypoxia (P < 0.001). This demonstrates that exposure to late gestation isolated chronic fetal hypoxia has the potential to alter the development of the autonomic nervous system control of FHRV in sheep. This presents a potential mechanism by which a reduction in indices of FHRV in human fetuses affected by uteroplacental dysfunction can predict fetuses at increased risk.

Vascular aging and cardiac maladaptation in growth-restricted preterm infants.

OBJECTIVE: To assess arterial morphology and mechanics in preterm infants with fetal growth restriction (FGR) compared with those appropriate for gestational age (AGA) in the early neonatal period. STUDY DESIGN: This observational study involved 20 preterm FGR infants (28 to 32 weeks) of gestational age (GA) and birth weight (BW) <10th centile and 20 preterm AGA infants. Vascular ultrasound was performed to measure aortic properties. RESULTS: GA and BW of FGR and AGA infants were 29.8±1.3 vs 30±0.9 weeks (P=0.78) and 923.4±168 vs 1403±237 g (P<0.001), respectively. At 10.5±1.3 (s.d.) days after birth, blood pressure (systolic 51±3 vs 46±4 mm Hg, P<0.001) and maximum aorta intima-media thickness (621±76 vs 479±54 µm; P<0.001) were significantly higher in FGR infants. Arterial wall stiffness and peripheral resistance were also increased in the FGR infants (2.36±0.24 vs 2.14±0.24, P=0.008 and 22.2±5 vs 13.7±2.3 mm Hg min ml-1, P<0.001), respectively. Significant correlations between vascular mechanics and cardiac function were observed (resistance vs E/E', r=0.7 and Tei index, r=0.79). CONCLUSION: Maladaptive arterial-ventricular coupling was noted. Early detection may aid in early therapeutic strategies such as afterload reduction.

Does growth restriction increase the vulnerability to acute ventilation-induced brain injury in newborn lambs? Implications for future health and disease.

Fetal growth restriction (FGR) and preterm birth are frequent co-morbidities, both are independent risks for brain injury. However, few studies have examined the mechanisms by which preterm FGR increases the risk of adverse neurological outcomes. We aimed to determine the effects of prematurity and mechanical ventilation (VENT) on the brain of FGR and appropriately grown (AG, control) lambs. We hypothesized that FGR preterm lambs are more vulnerable to ventilation-induced acute brain injury. FGR was surgically induced in fetal sheep (0.7 gestation) by ligation of a single umbilical artery. After 4 weeks, preterm lambs were euthanized at delivery or delivered and ventilated for 2 h before euthanasia. Brains and cerebrospinal fluid (CSF) were collected for analysis of molecular and structural indices of early brain injury. FGRVENT lambs had increased oxidative cell damage and brain injury marker S100B levels compared with all other groups. Mechanical ventilation increased inflammatory marker IL-8 within the brain of FGRVENT and AGVENT lambs. Abnormalities in the neurovascular unit and increased blood-brain barrier permeability were observed in FGRVENT lambs, as well as an altered density of vascular tight junctions markers. FGR and AG preterm lambs have different responses to acute injurious mechanical ventilation, changes which appear to have been developmentally programmed in utero.

Betamethasone-exposed preterm birth does not impair insulin action in adult sheep.

Preterm birth is associated with increased risk of type 2 diabetes (T2D) in adulthood; however, the underlying mechanisms are poorly understood. We therefore investigated the effect of preterm birth at ~0.9 of term after antenatal maternal betamethasone on insulin sensitivity, secretion and key determinants in adulthood, in a clinically relevant animal model. Glucose tolerance and insulin secretion (intravenous glucose tolerance test) and whole-body insulin sensitivity (hyperinsulinaemic euglycaemic clamp) were measured and tissue collected in young adult sheep (14 months old) after epostane-induced preterm (9M, 7F) or term delivery (11M, 6F). Glucose tolerance and disposition, insulin secretion, ß-cell mass and insulin sensitivity did not differ between term and preterm sheep. Hepatic PRKAG2 expression was greater in preterm than in term males (P = 0.028), but did not differ between preterm and term females. In skeletal muscle, SLC2A4 (P = 0.019), PRKAA2 (P = 0.021) and PRKAG2 (P = 0.049) expression was greater in preterm than in term overall and in males, while INSR (P = 0.047) and AKT2 (P = 0.043) expression was greater in preterm than in term males only. Hepatic PRKAG2 expression correlated positively with whole-body insulin sensitivity in males only. Thus, preterm birth at 0.9 of term after betamethasone does not impair insulin sensitivity or secretion in adult sheep, and has sex-specific effects on gene expression of the insulin signalling pathway. Hence, the increased risk of T2D in preterm humans may be due to factors that initiate preterm delivery or in early neonatal exposures, rather than preterm birth per se.

Fetal in vivo continuous cardiovascular function during chronic hypoxia.

Although the fetal cardiovascular defence to acute hypoxia and the physiology underlying it have been established for decades, how the fetal cardiovascular system responds to chronic hypoxia has been comparatively understudied. We designed and created isobaric hypoxic chambers able to maintain pregnant sheep for prolonged periods of gestation under controlled significant (10% O2) hypoxia, yielding fetal mean P(aO2) levels (11.5 ± 0.6 mmHg) similar to those measured in human fetuses of hypoxic pregnancy. We also created a wireless data acquisition system able to record fetal blood flow signals in addition to fetal blood pressure and heart rate from free moving ewes as the hypoxic pregnancy is developing. We determined in vivo longitudinal changes in fetal cardiovascular function including parallel measurement of fetal carotid and femoral blood flow and oxygen and glucose delivery during the last third of gestation. The ratio of oxygen (from 2.7 ± 0.2 to 3.8 ± 0.8; P < 0.05) and of glucose (from 2.3 ± 0.1 to 3.3 ± 0.6; P < 0.05) delivery to the fetal carotid, relative to the fetal femoral circulation, increased during and shortly after the period of chronic hypoxia. In contrast, oxygen and glucose delivery remained unchanged from baseline in normoxic fetuses. Fetal plasma urate concentration increased significantly during chronic hypoxia but not during normoxia (Δ: 4.8 ± 1.6 vs. 0.5 ± 1.4 µmol l(-1), P<0.05). The data support the hypotheses tested and show persisting redistribution of substrate delivery away from peripheral and towards essential circulations in the chronically hypoxic fetus, associated with increases in xanthine oxidase-derived reactive oxygen species.