Pharyngeal biorhythms during oral milk challenge in high-risk infants: Do they predict chronic tube feeding?

BACKGROUND: Eating difficulties are common in high-risk neonatal intensive care unit (NICU) infants; mechanisms remain unclear. Crib-side pharyngo-esophageal motility testing is utilized to assess contiguous swallowing physiology, and cross-system interplay with cardio-respiratory rhythms. Aims were to: (1) identify whether distinct pharyngeal rhythms exist during oral milk challenge (OMC), and (2) develop a chronic tube feeding risk prediction model in high-risk infants. METHODS: Symptomatic NICU infants (N = 56, 29.7 ± 3.7 weeks birth gestation) underwent pharyngo-esophageal manometry with OMC at 40.9 ± 2.5 weeks postmenstrual age (PMA). Exploratory cluster data analysis (partitioning around k-medoids) was performed to identify patient groups using pharyngeal contractile rhythm data (solitary swallows and swallows within bursts). Subsequently, (a) pharyngeal-esophageal, cardio-respiratory, and eating method characteristics were compared among patient groups using linear mixed models, and (b) chronic tube feeding prediction model was created using linear regression. RESULTS: Three distinct patient groups were identified with validity score of 0.6, and termed sparse (high frequency of solitary swallows), intermediate, or robust (high swallow rate within bursts). Robust group infants had: lesser pharyngeal and esophageal variability, greater deglutition apnea, pharyngeal activity, and esophageal activity (all p < 0.05), but less frequent heart rate decreases (p < 0.05) with improved clinical outcomes (milk transfer rate, p < 0.001, and independent oral feeding at discharge, p < 0.03). Chronic tube feeding risk = -11.37 + (0.22 × PMA) + (-0.73 × bronchopulmonary dysplasia) + (1.46 × intermediate group) + (2.57 × sparse group). CONCLUSIONS: Robust pharyngeal rhythm may be an ideal neurosensorimotor biomarker of independent oral feeding. Differential maturation of cranial nerve-mediated excitatory and inhibitory components involving foregut, airway, and cardiac rhythms distinguishes the physiologic and pathophysiologic basis of swallowing and cardio-respiratory adaptation.

Characterization of Esophageal and Sphincter Reflexes across Maturation in Dysphagic Infants with Oral Feeding Success vs Infants requiring Gastrostomy.

To test the hypothesis that esophageal and sphincteric sensory-motor reflexes are distinct across maturation in infants with dysphagia receiving gastrostomy-tube (G-tube). This is a retrospective review of 29 dysphagic infants (N = 15 study requiring gastrostomy, N = 14 age matched control achieving oral feeds) that underwent longitudinal pharyngeal-esophageal manometry at 42.3 (37-50.2) weeks postmenstrual age (PMA) and 48.9 (43.3-57.9) weeks PMA. Graded stimuli (0.1-5 mL) of varying media (air, water, and apple juice) tested esophageal peristaltic reflex, upper esophageal sphincter contractile reflex (UESCR), and lower esophageal sphincter relaxation reflex (LESRR). Comparisons were performed between study and controls and across maturation (time-1 vs time-2). Data represented as mean ± SE or OR (95% CI). Across maturation (time-1 vs time-2): Study infants did not exhibit significant differences across in peristaltic, UES, or LES reflexes (all p > 0.05). In contrast, controls exhibited increased UES resting pressure (13 ± 3 vs 17 ± 3 mmHg, p = 0.001), LES resting pressure (22 ± 3 vs 25 ± 3 mmHg, p < 0.009), LES nadir pressure (0.5 ± 1 vs 4.3 ± 1 mmHg, p = 0.001), and esophago-deglutition responses [2.5 (1.23-4.88), p = 0.04], and decreased secondary peristalsis [0.44 (0.31-0.61), p = 0.001], UESCR [0.4 (0.25-0.65), p = 0.001], LESRR [0.4 (0.24-0.75), p = 0.01], and symptoms [0.6 (0.45-0.83), p = 0.005]. Among infants with dysphagia, esophageal provocation induced peristaltic reflex, UESCR, and LESRR advance with longitudinal maturation when infants are oral-fed successfully, but not in those who received gastrostomy. Underlying mechanisms may be related to esophageal sensitivity, afferent or efferent transmission, and coordination of upstream excitation and downstream inhibition, which can be potential therapeutic targets for improving feeding capabilities after gastrostomy placement in infants with dysphagia.

Prophylactic Indomethacin in extremely preterm infants: association with death or BPD and observed early serum creatinine levels.

OBJECTIVES: To identify the relationship between prophylactic indomethacin (PI) administration and (1) mortality and bronchopulmonary dysplasia (BPD) at 36-week postmenstrual age (PMA) (primary outcome), and (2) to evaluate for PI-associated acute kidney injury. STUDY DESIGN: Retrospective cohort investigation of 22-28 weeks gestation infants (N = 1167) who were admitted to Nationwide Children's Hospital on postnatal days 0-1 between May 2009 and September 2017 and survived ≥24-h postnatal. The associations of PI treatment with mortality or BPD, and other secondary outcomes, were evaluated via multivariable robust-error-variance Poisson regression. RESULTS: The adjusted risks of death or BPD (1.02, 95% CI: 0.83, 1.25), BPD (0.97, 95% CI: 0.77, 1.21), and death 1.33 (95% CI: 0.84, 2.10) by 36-week PMA were unchanged following PI treatment after multivariable adjustment. No changes in mean creatinine levels were detected in exposed versus unexposed infants to suggest PI-induced AKI. CONCLUSION: Prophylactic indomethacin treatment was unrelated to mortality or BPD outcomes.

Infant Pulmonary Function Testing and Phenotypes in Severe Bronchopulmonary Dysplasia.

BACKGROUND: The definition of severe bronchopulmonary dysplasia (sBPD) is based on respiratory support needs. The management of a patient with sBPD remains empirical and is highly variable among providers. Our objective in this study was to test the hypothesis that infant pulmonary function testing (iPFT) would reveal distinct phenotypes in patients with established sBPD during the initial NICU stay. METHODS: A prospective cohort study with data prospectively collected on infants with sBPD from May 1, 2003, to June 30, 2016. iPFT data were used to classify the patients as obstructive, restrictive, or mixed. RESULTS: The median gestational age at birth was 25 weeks (interquartile range [IQR], 24-27 weeks) and the median birth weight was 707 g (IQR, 581-925 g). At the time of iPFT, the median postmenstrual age was 52 weeks (IQR, 45-63 weeks), and the median weight was 4.4 kg (IQR, 3.7-6.0 kg). There were 56 (51%) patients with obstructive, 44 (40%) with mixed, and 10 (9%) with restrictive phenotypes. Moderate or severe obstruction was seen in 86% of the obstructive group and 78% of the mixed group. Of the restrictive patients, 70% had moderate and 30% had mild restriction. Bronchodilator response was seen in 74% of obstructive, 63% of mixed, and 25% of restrictive patients. CONCLUSIONS: Our findings reveal that sBPD as it is currently defined includes distinct phenotypes. Future researchers of diagnostic approaches to this population should consider the development of bedside tests to define phenotypes, and researchers in future therapeutic trials should consider the use of pulmonary function phenotyping in patient recruitment.

Not All Children with Cystic Fibrosis Have Abnormal Esophageal Neutralization during Chemical Clearance of Acid Reflux.

PURPOSE: Acid neutralization during chemical clearance is significantly prolonged in children with cystic fibrosis, compared to symptomatic children without cystic fibrosis. The absence of available reference values impeded identification of abnormal findings within individual patients with and without cystic fibrosis. The present study aimed to test the hypothesis that significantly more children with cystic fibrosis have acid neutralization durations during chemical clearance that fall outside the physiological range. METHODS: Published reference value for acid neutralization duration during chemical clearance (determined using combined impedance/pH monitoring) was used to assess esophageal acid neutralization efficiency during chemical clearance in 16 children with cystic fibrosis (3 to <18 years) and 16 age-matched children without cystic fibrosis. RESULTS: Duration of acid neutralization during chemical clearance exceeded the upper end of the physiological range in 9 of 16 (56.3%) children with and in 3 of 16 (18.8%) children without cystic fibrosis (p=0.0412). The likelihood ratio for duration indicated that children with cystic fibrosis are 2.1-times more likely to have abnormal acid neutralization during chemical clearance, and children with abnormal acid neutralization during chemical clearance are 1.5-times more likely to have cystic fibrosis. CONCLUSION: Significantly more (but not all) children with cystic fibrosis have abnormally prolonged esophageal clearance of acid. Children with cystic fibrosis are more likely to have abnormal acid neutralization during chemical clearance. Additional studies involving larger sample sizes are needed to address the importance of genotype, esophageal motility, composition and volume of saliva, and gastric acidity on acid neutralization efficiency in cystic fibrosis children.

Feeding Methods at Discharge Predict Long-Term Feeding and Neurodevelopmental Outcomes in Preterm Infants Referred for Gastrostomy Evaluation.

OBJECTIVE: To test the hypothesis that oral feeding at first neonatal intensive care unit discharge is associated with less neurodevelopmental impairment and better feeding milestones compared with discharge with a gastrostomy tube (G-tube). STUDY DESIGN: We studied outcomes for a retrospective cohort of 194 neonates <37 weeks' gestation referred for evaluation and management of feeding difficulties between July 2006 and July 2012. Discharge milestones, length of hospitalization, and Bayley Scales of Infant Development-Third Edition scores at 18-24 months were examined. χ2, Mann-Whitney U, or t tests and multivariable logistic regression models were used. RESULTS: A total of 60% (n = 117) of infants were discharged on oral feedings; of these, 96% remained oral-fed at 1 year. The remaining 40% (n = 77) were discharged on G-tube feedings; of these, 31 (40%) remained G-tube dependent, 17 (22%) became oral-fed, and 29 (38%) were on oral and G-tube feedings at 1 year. Infants discharged on a G-tube had lower cognitive (P <.01), communication (P = .03), and motor (P <.01) composite scores. The presence of a G-tube, younger gestation, bronchopulmonary dysplasia, or intraventricular hemorrhage was associated significantly with neurodevelopmental delay. CONCLUSIONS: For infants referred for feeding concerns, G-tube evaluations, and feeding management, the majority did not require a G-tube. Full oral feeding at first neonatal intensive care unit discharge was associated with superior feeding milestones and less long-term neurodevelopmental impairment, relative to full or partial G-tube feeding. Evaluation and feeding management before and after G-tube placement may improve long-term feeding and neurodevelopmental outcomes.

Effect of nasal noninvasive respiratory support methods on pharyngeal provocation-induced aerodigestive reflexes in infants.

The pharynx is a locus of provocation among infants with aerodigestive morbidities manifesting as dysphagia, life-threatening events, aspiration-pneumonia, atelectasis, and reflux, and such infants often receive nasal respiratory support. We determined the impact of different oxygen delivery methods on pharyngeal stimulation-induced aerodigestive reflexes [room air (RA), nasal cannula (NC), and nasal continuous positive airway pressure (nCPAP)] while hypothesizing that the sensory motor characteristics of putative reflexes are distinct. Thirty eight infants (28.0 ± 0.7 wk gestation) underwent pharyngoesophageal manometry and respiratory inductance plethysmography to determine the effects of graded pharyngeal stimuli (n = 271) on upper and lower esophageal sphincters (UES, LES), swallowing, and deglutition-apnea. Comparisons were made between NC (n = 19), nCPAP (n = 9), and RA (n = 10) groups. Importantly, NC or nCPAP (vs. RA) had: 1) delayed feeding milestones (P < 0.05), 2) increased pharyngeal waveform recruitment and duration, greater UES nadir pressure, decreased esophageal contraction duration, decreased distal esophageal contraction amplitude, and decreased completely propagated esophageal peristalsis (all P < 0.05), and 3) similarly developed UES contractile and LES relaxation reflexes (P > 0.05). We conclude that aerodigestive reflexes were similarly developed in infants using noninvasive respiratory support with adequate upper and lower aerodigestive protection. Increased concern for GERD is unfounded in this population. These infants may benefit from targeted oromotor feeding therapies and safe pharyngeal bolus transit to accelerate feeding milestones.

Systematic Review of Inhaled Bronchodilator and Corticosteroid Therapies in Infants with Bronchopulmonary Dysplasia: Implications and Future Directions.

BACKGROUND: There is much debate surrounding the use of inhaled bronchodilators and corticosteroids for infants with bronchopulmonary dysplasia (BPD). OBJECTIVE: The objective of this systematic review was to identify strengths and knowledge gaps in the literature regarding inhaled therapies in BPD and guide future research to improve long-termoutcomes. METHODS: The databases of Academic Search Complete, CINAHL, PUBMED/MEDLINE, and Scopus were searched for studies that evaluated both acute and long-term clinical outcomes related to the delivery and therapeutic efficacy of inhaled beta-agonists, anticholinergics and corticosteroids in infants with developing and/or established BPD. RESULTS: Of 181 articles, 22 met inclusion criteria for review. Five evaluated beta-agonist therapies (n = 84, weighted gestational age (GA) of 27.1(26-30) weeks, weighted birth weight (BW) of 974(843-1310) grams, weighted post menstrual age (PMA) of 34.8(28-39) weeks, and weighted age of 53(15-86) days old at the time of evaluation). Fourteen evaluated inhaled corticosteroids (n = 2383, GA 26.2(26-29) weeks, weighted BW of 853(760-1114) grams, weighted PMA of 27.0(26-31) weeks, and weighted age of 6(0-45) days old at time of evaluation). Three evaluated combination therapies (n = 198, weighted GA of 27.8(27-29) weeks, weighted BW of 1057(898-1247) grams, weighted PMA of 30.7(29-45) weeks, and age 20(10-111) days old at time of evaluation). CONCLUSION: Whether inhaled bronchodilators and inhaled corticosteroids improve long-term outcomes in BPD remains unclear. Literature regarding these therapies mostly addresses evolving BPD. There appears to be heterogeneity in treatment responses, and may be related to varying modes of administration. Further research is needed to evaluate inhaled therapies in infants with severe BPD. Such investigations should focus on appropriate definitions of disease and subject selection, timing of therapies, and new drugs, devices and delivery methods as compared to traditional methods across all modalities of respiratory support, in addition to the assessment of long-term outcomes of initial responders.

Sildenafil Treatment of Infants With Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension.

OBJECTIVE: This study had 2 goals: (1) to identify clinical and demographic characteristics associated with sildenafil exposure for infants with bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH); and (2) to characterize hospital-specific treatment frequency, age at first administration, and length of sildenafil treatment. METHODS: This retrospective cohort study used data from the Pediatric Health Information System to determine variables associated with sildenafil exposure and between-hospital variations in sildenafil utilization patterns. The study included infants with BPD-PH who were discharged between January 1, 2006, and December 31, 2013. RESULTS: Within 36 US pediatric hospitals, 3720 infants were diagnosed with BPD, of whom 598 (16%) also had a diagnosis of PH (BPD-PH). Among infants with BPD-PH, 104 infants (17%) received sildenafil. The odds for sildenafil treatment among infants born between 25 and 26 weeks' gestational age (GA) and <24 weeks' GA, respectively, were 2.26 (95% confidence interval [CI]: 1.20-4.24) and 3.21 (95% CI: 1.66-6.21) times those of infants born at 27 to 28 weeks' GA. Severity of BPD correlated with sildenafil exposure, with adjusted odds ratios (ORs) for moderate BPD (OR: 3.03 [95% CI: 1.03-8.93]) and severe BPD (OR: 7.56 [95% CI: 2.50-22.88]), compared with mild BPD. Greater rates of sildenafil exposure were observed among small for GA neonates (OR: 2.32 [95% CI: 1.21-4.46]). The proportion of infants with BPD-PH exposed to sildenafil varied according to hospital (median: 15%; 25th-75th percentile: 0%-25%), as did the median duration of therapy (52 days; 25th-75th percentile: 28-109 days). CONCLUSIONS: The odds of sildenafil treatment were greatest among the most premature infants with severe forms of BPD. The frequency and duration of sildenafil exposure varied markedly according to institution. Patient-centered trials for infants with BPD-PH are needed to develop evidence-based practices.

Mechanisms of cough provocation and cough resolution in neonates with bronchopulmonary dysplasia.

BACKGROUND: Cough and deglutition are protective mechanisms that defend against aspiration. We identified mechanisms associated with cough provocation as well as those associated with cough resolution in infants with bronchopulmonary dysplasia (BPD). METHODS: Manometry signatures of cough were recognized in 16 premature infants with BPD undergoing concurrent esophageal manometry, respiratory inductance plethysmography, and nasal air flow measurements. Pretussive and post-tussive pharyngo-esophageal motility changes were analyzed. Mechanisms associated with cough and mechanisms that restored respiratory and esophageal normalcy were analyzed. RESULTS: We analyzed 312 cough events during 88 cough clusters; 97% were associated with recognizable manometric patterns. Initial mechanisms related with coughing included nonpropagating swallow (59%), upper esophageal sphincter (UES) reflex contraction (18%), and lower esophageal sphincter (LES) relaxation (14%). UES and LES dysfunction was present in 69% of nonpropagating swallow-associated cough clusters. Mechanisms restoring post-tussive normalcy included primary peristalsis (84%), secondary peristalsis (8%), and none recognized (8%). UES contraction reflex was associated with cough clusters more frequently in infants on nasal continuous positive airway pressure (NCPAP) (OR = 9.13, 95% CI = 1.88-44.24). CONCLUSION: Cough clusters in infants with BPD had identifiable etiologies associated with esophageal events; common initial mechanisms were of upper aerodigestive origin, while common clearing mechanisms were peristaltic reflexes.

Antecedent Predictors of Feeding Outcomes in Premature Infants With Protracted Mechanical Ventilation.

OBJECTIVES: The aim of the present study was to define risk factors associated with gastrostomy in premature infants receiving protracted mechanical ventilation (≥30 days). METHODS: Retrospective data collected on 170 preterm neonates (birth weight <1500 g) who received uninterrupted mechanical ventilation for ≥30 days were analyzed with logistic regression methods to predict the association of gastrostomy with cardiorespiratory, infectious, and neurological morbidities. RESULTS: A total of 32 of 170 infants had gastrostomy tubes. Including all of the covariates in 1 model, duration of cumulative ventilation (P < 0.001) and uninterrupted ventilation (P < 0.001), and ventriculoperitoneal shunt (P = 0.02) were significant predictors, whereas sepsis, intraventrical hemorrhage grade III or IV, and patent ductus arteriosus ligation were not. Respiratory severity score (mean airway pressure × fraction of inspired oxygen) calculated at 30 days of life was also a significant predictor (P = 0.01). CONCLUSIONS: In infants with protracted mechanical ventilation, the degree of respiratory support at 1 month of age, prolonged respiratory morbidity, and neuropathology are the significant predictors for gastrostomy.

Safety and Efficacy of Oral Feeding in Infants with BPD on Nasal CPAP.

Safety and efficacy of oral feeding was examined in infants with bronchopulmonary dysplasia (BPD) on nasal continuous positive airway pressure (NCPAP). We hypothesized that repetitive oral feeding enhances aero-digestive outcomes and reduces resource utilization. Data from infants with BPD (37-42 weeks post menstrual age) that were orally fed while on NCPAP (n = 26) were compared with those that were exclusively gavage fed on NCPAP (n = 27). Subject assignment was random and physician practice based. Specifically, we compared the differences in aero-digestive milestones, resource utilization, and safety metrics. Demographic characteristics such as gender distribution, gestational age, and birth weight, clinical characteristics such as frequency of intraventricular hemorrhage and patent ductus arteriosus needing surgical ligation were similar in both groups (p > 0.05). Characteristics of respiratory support and airway milestones were similar in both groups (p > 0.05). However, infants in NCPAP-oral fed group had earlier acquisition of full oral feeding milestone by 17 days (median) versus infants who were not orally fed during NCPAP (p < 0.05). Discharge weights and the frequency of gastrostomy tube placement were also similar in both groups (p > 0.05). There were no tracheostomies in either group. There was no incidence of clinically significant aspiration pneumonia in infants during the period of the oral feeding while on NCPAP. Controlled introduction of oral feedings in infants with BPD during NCPAP is safe and may accelerate the acquisition of oral feeding milestones.

Utilization of inhaled corticosteroids for infants with bronchopulmonary dysplasia.

OBJECTIVE: To determine demographic and clinical variables associated with inhaled corticosteroid administration and to evaluate between-hospital variation in inhaled steroid use for infants with bronchopulmonary dysplasia (BPD). DESIGN: Retrospective Cohort Study. SETTING: Neonatal units of 35 US children's hospitals; as recorded in the Pediatric Health Information System (PHIS) database. PATIENTS: 1429 infants with evolving BPD at 28 days who were born at <29 weeks gestation with birth weight <1500 grams, admitted within the first 7 postnatal days, and discharged between January 2007-June 2011. RESULTS: Inhaled steroids were prescribed to 25% (n = 352) of the cohort with use steadily increasing during the first two months of hospitalization. The most frequently prescribed steroid was beclomethasone (n = 194, 14%), followed by budesonide (n = 125, 9%), and then fluticasone (n = 90, 6%). Birth gestation <24 weeks, birth weight 500-999 grams, and prolonged ventilation all increased the adjusted odds of ever receiving inhaled corticosteroids (p<0.05). Wide variations between hospitals in the frequency of infants ever receiving inhaled steroids (range: 0-60%) and the specific drug prescribed were noted. This variation persisted, even after controlling for observed confounders. CONCLUSIONS: Inhaled corticosteroid administration to infants with BPD is common in neonatal units within U.S. Children's hospitals. However, its utilization varies markedly between centers from no treatment at some institutions to the majority of infants with BPD being treated at others. This supports the need for further research to identify the benefits and potential risks of inhaled steroid usage in infants with BPD.

Practice Variance, Prevalence, and Economic Burden of Premature Infants Diagnosed With GERD.

OBJECTIVE: To determine the practice variance, prevalence, and economic burden of clinically diagnosed gastroesophageal reflux disease (GERD) in preterm infants. METHODS: Applying a retrospective cohort study design, we analyzed data from 18 567 preterm infants of 22 to 36 weeks' gestation and >400 g birth weight from the NICUs of 33 freestanding children's hospitals in the United States. GERD prevalence, comorbidities, and demographic factors were examined for their association with average length of stay (LOS) and hospitalization cost. RESULTS: Overall, 10.3% of infants received a diagnosis of GERD (95% confidence interval [CI]: 9.8-10.7). There was a 13-fold variation in GERD rates across hospitals (P < .001). GERD diagnosis was significantly (P < .05) associated with bronchopulmonary dysplasia and necrotizing enterocolitis, as well as congenital anomalies and decreased birth weight. GERD diagnosis was associated with $70 489 (95% CI: 62 184-78 794) additional costs per discharge and 29.9 additional days in LOS (95% CI: 27.3-32.5). CONCLUSIONS: One in 10 of these premature NICU infants were diagnosed with GERD, which is associated with substantially increased LOS and elevated costs. Better diagnostic and management strategies are needed to evaluate reflux-type symptoms in this vulnerable NICU population.

Esophageal disease in pediatrics.

The following on esophageal disease in pediatrics contains commentaries on acquisition of neuromuscular maturation; physiology of esophageal peristaltic and sphincteric reflexes; implications for clinical practice; and conditions that predispose to severe gastroesophageal reflux disease (GERD) in children with potential risk for esophageal cancer.

Spatiotemporal characteristics of acid refluxate and relationship to symptoms in premature and term infants with chronic lung disease.

BACKGROUND AND OBJECTIVES: The prevalence of gastroesophageal reflux (GER) is high among infants with chronic lung disease (CLD), and the associated pathogenic mechanisms are not clear. The relationship of symptoms to the extent or duration of acid reflux events (AREs) is not well known in preterm or term infants. Our aim was to evaluate the relationship between spatial (height) and temporal (duration) characteristics of AREs (pH <4.0) with symptoms in CLD. We tested the hypothesis that in infants with CLD, AREs into the pharynx are associated with increased symptom occurrence and delayed clearance. METHODS: Nine infants born at 29.8 +/- 5.5 wk gestation (mean +/- SD, range 24.7-39.0 wk) with CLD were evaluated for GER at 49.7 +/- 8.0 wk postmenstrual age (mean +/- SD, range 39.9-67.4 wk). Esophageal manometry was first performed to determine the nares-lower esophageal sphincter (LES) distance. A pH-impedance probe was placed at 87% of the nares-LES distance, and a recording was performed for about 24 h at cribside. Symptoms (respiratory, sensory, and movement) were documented by nurses that were blinded to the pH-impedance recordings. A symptom was considered associated with an ARE if it occurred 2 min before, during, or 2 min after the ARE. The proximal extent and associated clearance mechanisms were correlated with symptom sensitivity index (SSI = number of AREs with symptoms/total AREs *100). Multiple logistic regression methods, analysis of variance (ANOVA) models, and chi(2) tests were performed. Data are described as median, mean +/- SD, or %. RESULTS: A total of 511 AREs, based on pH-Impedance methods, were analyzed from 203 h of recordings in the nine infants. The distal esophagus was the maximal height reached in 80% of AREs (P < 0.001, compared to other esophageal segments). Overall 33% of the AREs were associated with symptoms, and an SSI of 77% was noted with high AREs into the pharynx. The average acid clearance time was prolonged with symptomatic AREs versus nonsymptomatic AREs by 3.5-fold (P < 0.001). CONCLUSIONS: The occurrence and frequency of symptoms with AREs depend on the most proximal extent of the ARE and the acid clearance time.

Correlation of glottal closure using concurrent ultrasonography and nasolaryngoscopy in children: a novel approach to evaluate glottal status.

OBJECTIVES: Endoscopic procedures to assess aerodigestive symptoms by evaluating glottal motion are not practical in neonates because of small nares, respiratory difficulties, or additional stress. Our objective was to determine the temporal correlation between concurrent nasolaryngoscopy (NLS) and ultrasonography (USG) evaluation of glottal motion. METHODS: Simultaneous USG of the glottis was performed in 10 subjects (5 males, 5 females, age = 4.5 months to 7.1 years) that underwent diagnostic flexible outpatient NLS. The USG transducer was placed on the anterior neck at the level of the vocal cords. The video signals from NLS and USG were integrated and synchronized into real-time cine loops of 1-min duration. RESULTS: Frame-by-frame evaluation of 10,800 frames identifying glottal opening and closure time was compared between the two modalities by three observers and the timing of glottal closure was marked. Two investigators, blinded to NLS images, identified ultrasonographically determined glottal closure with 99% and 100% accuracy, and the mean probability of missing a closure frame was 0.007 (95% CI = 0.0008-0.024). CONCLUSIONS: Temporal characteristics of glottal motion can be quantified by USG with perfect reliability and safety. This method can be useful in measuring the presence and the duration of laryngeal adduction.