Number of children in the household influences respiratory morbidities in children with bronchopulmonary dysplasia in the outpatient setting.

BACKGROUND: Bronchopulmonary dysplasia (BPD), a common complication of prematurity, is associated with outpatient morbidities, including respiratory exacerbations. Daycare attendance is associated with increased rates of acute and chronic morbidities in children with BPD. We sought to determine if additional children in the household conferred similar risks for children with BPD. METHODS: The number of children in the household and clinical outcomes were obtained via validated instruments for 933 subjects recruited from 13 BPD specialty clinics in the United States. Clustered logistic regression models were used to test for associations. RESULTS: The mean gestational age of the study population was 26.5 ± 2.2 weeks and most subjects (69.1%) had severe BPD. The mean number of children in households (including the subject) was 2.1 ± 1.3 children. Each additional child in the household was associated with a 13% increased risk for hospital admission, 13% increased risk for antibiotic use for respiratory illnesses, 10% increased risk for coughing/wheezing/shortness of breath, 14% increased risk for nighttime symptoms, and 18% increased risk for rescue medication use. Additional analyses found that the increased risks were most prominent when there were three or more other children in the household. CONCLUSIONS: We observed that additional children in the household were a risk factor for adverse respiratory outcomes. We speculate that secondary person-to-person transmission of respiratory viral infections drives this finding. While this risk factor is not easily modified, measures do exist to mitigate this disease burden. Further studies are needed to define best practices for mitigating this risk associated with household viral transmission.

Respiratory Outcomes for Ventilator-Dependent Children With Bronchopulmonary Dysplasia.

OBJECTIVES: To describe outpatient respiratory outcomes and center-level variability among children with severe bronchopulmonary dysplasia (BPD) who require tracheostomy and long-term mechanical ventilation. METHODS: Retrospective cohort of subjects with severe BPD, born between 2016 and 2021, who received tracheostomy and were discharged on home ventilator support from 12 tertiary care centers participating in the BPD Collaborative Outpatient Registry. Timing of key respiratory events including time to tracheostomy placement, initial hospital discharge, first outpatient clinic visit, liberation from the ventilator, and decannulation were assessed using Kaplan-Meier analysis. Differences between centers for the timing of events were assessed via log-rank tests. RESULTS: There were 155 patients who met inclusion criteria. Median age at the time of the study was 32 months. The median age of tracheostomy placement was 5 months (48 weeks' postmenstrual age). The median ages of hospital discharge and first respiratory clinic visit were 10 months and 11 months of age, respectively. During the study period, 64% of the subjects were liberated from the ventilator at a median age of 27 months and 32% were decannulated at a median age of 49 months. The median ages for all key events differed significantly by center (P ≤ .001 for all events). CONCLUSIONS: There is wide variability in the outpatient respiratory outcomes of ventilator-dependent infants and children with severe BPD. Further studies are needed to identify the factors that contribute to variability in practice among the different BPD outpatient centers, which may include inpatient practices.

Validation of an outpatient questionnaire for bronchopulmonary dysplasia control.

INTRODUCTION: Despite bronchopulmonary dysplasia (BPD) being a common morbidity of preterm birth, there is no validated objective tool to assess outpatient respiratory symptom control for clinical and research purposes. METHODS: Data were obtained from 1049 preterm infants and children seen in outpatient BPD clinics of 13 US tertiary care centers from 2018 to 2022. A new standardized instrument was modified from an asthma control test questionnaire and administered at the time of clinic visits. External measures of acute care use were also collected. The questionnaire for BPD control was validated in the entire population and selected subgroups using standard methodology for internal reliability, construct validity, and discriminative properties. RESULTS: Based on the scores from BPD control questionnaire, the majority of caregivers (86.2%) felt their child's symptoms were under control, which did not differ by BPD severity (p = 0.30) or a history of pulmonary hypertension (p = 0.42). Across the entire population and selected subgroups, the BPD control questionnaire was internally reliable, suggestive of construct validity (albeit correlation coefficients were -0.2 to -0.4.), and discriminated control well. Control categories (controlled, partially controlled, and uncontrolled) were also predictive of sick visits, emergency department visits, and hospital readmissions. CONCLUSION: Our study provides a tool for assessing respiratory control in children with BPD for clinical care and research studies. Further work is needed to identify modifiable predictors of disease control and link scores from the BPD control questionnaire to other measures of respiratory health such as lung function testing.

Daycare Attendance is Linked to Increased Risk of Respiratory Morbidities in Children Born Preterm with Bronchopulmonary Dysplasia.

OBJECTIVES: To test the hypothesis that daycare attendance among children with bronchopulmonary dysplasia (BPD) is associated with increased chronic respiratory symptoms and/or greater health care use for respiratory illnesses during the first 3 years of life. STUDY DESIGN: Daycare attendance and clinical outcomes were obtained via standardized instruments for 341 subjects recruited from 9 BPD specialty clinics in the US. All subjects were former infants born preterm (<34 weeks) with BPD (71% severe) requiring outpatient follow-up between 0 and 3 years of age. Mixed logistic regression models were used to test for associations. RESULTS: Children with BPD attending daycare were more likely to have emergency department visits and systemic steroid usage. Children in daycare up to 3 years of age also were more likely to report trouble breathing, having activity limitations, and using rescue medications when compared with children not in daycare. More severe manifestations were found in children attending daycare between 6 and 12 months of chronological age. CONCLUSIONS: In this study, children born preterm with BPD who attend daycare were more likely to visit the emergency department, use systemic steroids, and have chronic respiratory symptoms compared with children not in daycare, indicating that daycare may be a potential modifiable risk factor to minimize respiratory morbidities in children with BPD during the preschool years.

Insurance coverage and respiratory morbidities in bronchopulmonary dysplasia.

INTRODUCTION: Preterm infants and young children with bronchopulmonary dysplasia (BPD) are at increased risk for acute care utilization and chronic respiratory symptoms during early life. Identifying risk factors for respiratory morbidities in the outpatient setting could decrease the burden of care. We hypothesized that public insurance coverage was associated with higher acute care usage and respiratory symptoms in preterm infants and children with BPD after initial neonatal intensive care unit (NICU) discharge. METHODS: Subjects were recruited from BPD clinics at 10 tertiary care centers in the United States between 2018 and 2021. Demographics and clinical characteristics were obtained through chart review. Surveys for clinical outcomes were administered to caregivers. RESULTS: Of the 470 subjects included in this study, 249 (53.0%) received employer-based insurance coverage and 221 (47.0%) received Medicaid as sole coverage at least once between 0 and 3 years of age. The Medicaid group was twice as likely to have sick visits (adjusted odd ratio [OR]: 2.06; p = 0.009) and emergency department visits (aOR: 2.09; p = 0.028), and three times more likely to be admitted for respiratory reasons (aOR: 3.04; p = 0.001) than those in the employer-based group. Additionally, those in the Medicaid group were more likely to have nighttime respiratory symptoms (aOR: 2.62; p = 0.004). CONCLUSIONS: Children with BPD who received Medicaid coverage were more likely to utilize acute care and have nighttime respiratory symptoms during the first 3 years of life. More comprehensive studies are needed to determine whether the use of Medicaid represents a barrier to accessing care, lower socioeconomic status, and/or a proxy for detrimental environmental exposures.

Characteristics of infants or children presenting to outpatient bronchopulmonary dysplasia clinics in the United States.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is a common respiratory sequelae of preterm birth, for which longitudinal outpatient data are limited. Our objective was to describe a geographically diverse outpatient cohort of former preterm infants followed in BPD-disease specific clinics. METHODS: Seven BPD specialty clinics contributed data using standardized instruments to this retrospective cohort study. Inclusion criteria included preterm birth (<37 weeks) and respiratory symptoms or needs requiring outpatient follow-up. RESULTS: A total of 413 preterm infants and children were recruited (mean age: 2.4 ± 2.7 years) with a mean gestational age of 27.0 ± 2.8 weeks and a mean birthweight of 951 ± 429 grams of whom 63.7% had severe BPD. Total, 51.1% of subjects were nonwhite. Severe BPD was not associated with greater utilization of acute care/therapies compared to non-severe counterparts. Of children with severe BPD, differences in percentage of those on any home respiratory support (p = .001), home positive pressure ventilation (p = .003), diuretics (p < .001), inhaled corticosteroids (p < .001), and pulmonary vasodilators (p < .001) were found between centers, however no differences in acute care use were observed. DISCUSSION: This examination of a multicenter collaborative registry of children born prematurely with respiratory disease demonstrates a diversity of management strategies among geographically distinct tertiary care BPD centers in the United States. This study reveals that the majority of children followed in these clinics were nonwhite and that neither variation in management nor severity of BPD at 36 weeks influenced outpatient acute care utilization. These findings suggest that post-neonatal intensive care unit factors and follow-up may modify respiratory outcomes in BPD, possibly independently of severity.

Tracheostomy in the pediatric trisomy 21 population.

INTRODUCTION: Tracheostomy in children is often performed to alleviate airway obstruction (AO) or to facilitate long-term ventilator support due to respiratory failure of various etiologies, such as heart failure, and postoperative respiratory failure. Although many of these pathologies are common among trisomy 21 patients, tracheostomy rates among this population have not previously been reported. The aim of our study was to determine the incidence of trisomy 21 patients undergoing tracheostomy. Secondary objectives include decannulation rates and mortality associated with tracheostomy. MATERIALS AND METHODS: A retrospective cohort study was conducted on pediatric trisomy 21 patients undergoing tracheostomy between 2004 and 2013. RESULTS: Twenty patients underwent tracheostomy at a median age of 7.1 months (interquartile range [IQR] = 3.5,21.3). The estimated incidence of tracheostomy in trisomy 21 patients among our tracheostomy population was 1.7% (20/1173) over 10 years. The most common indications were airway obstruction (AO) (55%), cardiac/pulmonary respiratory failure (CRF) (25%), or both (20%). Overall mortality was 30%, much lower among AO patients (9%) than CRF (40%) or both (60%), (P = 0.029). Nine patients (45%) were successfully decannulated, with median duration of cannulation of 2.2 years (IQR = 1.7,3). CONCLUSIONS: This study suggests a rate of tracheostomy in the pediatric trisomy 21 population approximately 3 times that of the general pediatric population. Over half in this cohort underwent tracheostomy for isolated AO, while the general pediatric tracheostomy population demonstrates a much higher prevalence of prematurity-related CRF. Overall mortality rate and decannulation rate approximated that of the general pediatric tracheostomy population, although outcomes were significantly poorer among patients trisomy 21 patients undergoing tracheostomy for CRF.

Implementation of Updated Hearing Screen Guidelines in a Level IV NICU-A Quality Improvement Project.

Hearing loss is the most common congenital birth defect. In 2007, American Academy of Pediatrics updated the hearing screen guidelines to recommend hearing screen by 1 month of age, diagnostic evaluation by 3 months, and early interventions by 6 months. Early interventions have been shown to improve developmental outcome in children with hearing loss. Infants admitted to the neonatal intensive care unit (NICU) are at higher risk for hearing loss. For infants born before 34 weeks' gestation, there are no guidelines for initial hearing screen. Although auditory brain stem response can be reliably performed at 32 to 34 weeks, in most NICUs, they are screened prior to discharge per universal hearing screen guidelines. In high-risk infants, often with prolonged hospitalization, this leads to missed opportunity for early detection and implementation of early intervention services. Using quality improvement methodology, an updated hearing screen algorithm was developed and implemented in our level IV NICU along with an electronic medical record tool to improve the process of identifying infants meeting criteria for hearing screen.

Successful Reversal of Furosemide-Induced Secondary Hyperparathyroidism With Cinacalcet.

Secondary hyperparathyroidism (SHPT) is a rare complication of furosemide therapy that can occur in patients treated with the loop diuretic for a long period of time. We report a 6-month-old 28-weeks premature infant treated chronically with furosemide for his bronchopulmonary dysplasia, who developed hypocalcemia and severe SHPT, adversely affecting his bones. Discontinuation of the loop diuretic and the addition of supplemental calcium and calcitriol only partially reversed the SHPT, bringing serum parathyroid hormone level down from 553 to 238 pg/mL. After introduction of the calcimimetic Cinacalcet, we observed a sustained normalization of parathyroid hormone concentration at 27 to 63 pg/mL and, with that correction, of all biochemical abnormalities and healing of the bone disease. No adverse effects were noted. We conclude that in cases of SHPT due to furosemide in which traditional treatment fails, there may be room to consider the addition of a calcimimetic agent.

A Novel Method of Measuring Fractional Exhaled Nitric Oxide in Tracheostomized Ventilator-Dependent Children.

BACKGROUND: The lower airway concentration of fractional exhaled nitric oxide (FENO) is unknown in children with chronic lung disease of infancy who have tracheostomy for long-term mechanical ventilation. We aimed to evaluate an online method of measuring FENO in a cohort of ventilator-dependent children with a tracheostomy and to explore the relationship between the peak FENO concentration (FENO peak) and the degree of respiratory support using the respiratory severity score. METHODS: We conducted a prospective cross-sectional study in 31 subjects who were receiving long-term respiratory support through a tracheostomy. We measured the FENO peak and FENO plateau concentration from the tip of the tracheostomy tube using a nitric oxide analyzer in subjects during a quiet state while being mechanically ventilated. We obtained 2 consecutive 2-min duration measurements from each subject. The FENO peak, exhaled NO output (equal to the FENO peak × minute ventilation), and pulmonary NO excretion (exhaled NO output/weight) were calculated and correlated with the respiratory severity score. RESULTS: The median FENO peak was 2.69 ppb, and the median FENO plateau was 1.57 ppb. The coefficients of repeatability between the 2 consecutive measurements for FENO peak and FENO plateau were 0.74 and 0.59, respectively. The intraclass coefficient between subjects within the cohort was 0.988 (95% CI 0.975-0.994, P < .001) for FENO peak and 0.991 (95% CI 0.982-0.996, P < .001) for FENO plateau. We found that the FENO peak was directly correlated with minute ventilation, but we did not find a direct relationship between the FENO peak concentration, exhaled NO output, or pulmonary NO excretion and respiratory severity score. CONCLUSIONS: FENO peak and plateau concentration can be measured online easily with a high degree of reliability and repeatability in infants and young children with a tracheostomy. FENO peak concentration from the lower airway is low and influenced by minute ventilation in children receiving mechanical ventilation.

Outcomes of Tracheostomy in Children Requiring Surgery for Congenital Heart Disease.

Outcomes after discharge in children requiring tracheostomy after cardiac surgery have not been fully described. A retrospective, single-center study was performed on all children <18 years of age requiring both tracheostomy and surgery for congenital heart disease from January 2002 to May 2015. Forty-six tracheostomies were placed after surgery and four before. Single-ventricle anatomy was present in 12 (33%) patients. Incidence of tracheostomy after heart surgery increased from 0.8% the first half of the study period to 2% the second half. Median time between cardiac surgery and tracheostomy was 58 days. The most common indication for tracheostomy was multifactorial (30%) followed by airway malacia (22%). Median length to follow-up for survivors was 3.9 years (range 0.4-11.8 years). Survival to hospital discharge was 72%, and intermediate survival was 48%. Survival in those with systemic to pulmonary artery shunts at the time of tracheostomy was 22% compared to 59% for those with biventricular anatomy. Heart failure and multiple indications for tracheostomy were associated with worse outcome. There was no difference in survival for those discharged with a ventilator compared to those that were not. The most common cause of death after discharge was tracheostomy tube dislodgement/obstruction, accounting for 5 of 11 that died. Survival with a tracheostomy after cardiac surgery is poor, and children with systemic to pulmonary artery shunts are at especially high risk of death.

Tracheobronchomalacia diagnosed by tracheobronchography in ventilator-dependent infants.

BACKGROUND: Tracheobronchomalacia prevalence in premature infants on prolonged mechanical ventilation is high. OBJECTIVE: To examine the prevalence of tracheobronchomalacia diagnosed by tracheobronchography in ventilator-dependent infants, and describe the demographic, clinical and dynamic airway characteristics of those infants with tracheobronchomalacia. MATERIALS AND METHODS: This retrospective review studies 198 tracheobronchograms performed from 1998 to 2011 in a cohort of 158 ventilator-dependent infants <2 years of age. Dynamic airway assessment during tracheobronchography determined the optimal positive end-expiratory pressure to maintain airway patency at expiration in those infants with tracheobronchomalacia. RESULTS: Tracheobronchograms were performed at a median age of 52 weeks post menstrual age. The primary diagnoses in these infants were bronchopulmonary dysplasia (53%), other causes of chronic lung disease of infancy (28%) and upper airway anomaly (13%). Of those with bronchopulmonary dysplasia, 48% had tracheobronchomalacia. Prematurity (P=0.01) and higher baseline - pre-tracheobronchogram positive end-expiratory pressure (P=0.04) were significantly associated with tracheobronchomalacia. Dynamic airway collapse during tracheobronchography showed statistically significant airway opening at optimal positive end-expiratory pressure (P < 0.001). There were no significant complications noted during and immediately following tracheobronchography. CONCLUSION: The overall prevalence of tracheobronchomalacia in this cohort of ventilator-dependent infants is 40% and in those with bronchopulmonary dysplasia is 48%. Infants born prematurely and requiring high pre-tracheobronchogram positive end-expiratory pressure were likely to have tracheobronchomalacia. Tracheobronchography can be used to safely assess the dynamic function of the airway and can provide the clinician the optimal positive end-expiratory pressure to maintain airway patency.

An unusual case of rapidly progressive hyperbilirubinemia.

We present an unusual case of hyperbilirubinemia with rapid early progression leading to bilirubin encephalopathy in a term neonate. Despite early recognition and intervention, the total serum bilirubin reached a maximum level of 39 mg/dL at 32 hours of life. Prior to an emergent exchange transfusion, the patient's diagnostic evaluation was significant for Coombs-negative microangiopathic hemolytic anemia and thrombocytopenia. Further testing revealed a deficiency of ADAMTS13 protein, or von Willebrand factor-cleaving protease, a finding diagnostic of congenital thrombotic thrombocytopenic purpura, or Upshaw-Schulman syndrome. This rare disease is often misdiagnosed, especially in the newborn period.

Lung pathology in premature infants with Ureaplasma urealyticum infection.

Respiratory tract colonization with Ureaplasma urealyticum in preterm infants has been associated with a higher incidence of pneumonia, severe respiratory failure, bronchopulmonary dysplasia (BPD), and death. In this report, we characterize the lung pathology and expression of tumor necrosis factor-alpha (TNF-alpha) associated with U. urealyticum pneumonia in very low-birth weight infants (VLBW; < or =1500 g). Lung pathology of archived autopsy specimens was retrospectively reviewed in three groups of VLBW infants: 5 gestational controls who died from nonpulmonary causes, 13 infants with pneumonia who were culture and/or PCR negative for U. urealyticum, and 5 infants with pulmonary disease and positive for U. urealyticum by tracheal aspirate and/or lung tissue culture or polymerase chain reaction (PCR). Presence and extent of alveolar macrophages and neutrophils, as well as interstitial lymphocytic infiltration and fibrosis were evaluated. PCR was performed on formalin-fixed, paraffin-embedded lung sections. Additional sections were immunostained for TNF-alpha. The peripheral total white blood cell counts and absolute neutrophil counts were three-fold higher in infants with U. urealyticum pneumonia than cell counts in infants infected with other organisms. There was a trend toward a predominance of neutrophils in alveoli of non- Ureaplasma pneumonia infants, but a trend toward a predominance of alveolar macrophages in U. urealyticum-infected infants. The most striking finding was the presence of increased interstitial fibrosis in all Ureaplasma-infected infants. TNF-alpha immunoreactive cell density was very low in the gestational controls, but increased in both pneumonia groups. We conclude that persistent lung U. urealyticum infection may contribute to chronic inflammation and early fibrosis in the preterm lung.