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BACKGROUND: Timely development of early motor skills is essential for later skill development in multiple domains. Infants with severe bronchopulmonary dysplasia (BPD) have significant risk for developmental delays. Early motor skill development in this population has not been described. The aim of the present study was to characterize motor skill acquisition at 3 and 6 months corrected age (CA) and assess trajectories of skill development over this time period in infants with severe BPD. METHODS: We performed a single-center, retrospective descriptive study. Motor skills were categorized as present and normal, present but atypical, or absent at 3 and 6 months CA. Logistic regression was used to identify clinical characteristics associated with negative trajectories of skill acquisition. RESULTS: Data were available for 232 infants and 187 infants at 3 and 6 months CA, respectively. Ten motor skills were present and normal in 5–44%(range) of subjects at 3 months. Nineteen motor skills were present and normal in 1–63%(range) of subjects at 6 months. Significant postural asymmetry was noted throughout the study period. Loss of skills and worsening asymmetries over time were common. Exposure to sedating medications was significantly associated with poor development. CONCLUSION: We report delays in motor skill acquisition and postural asymmetries in infants with severe BPD at both 3 and 6 months CA. The association between sedating medications and poor development suggests that efforts to limit these exposures may lead to improved development. Targeted interventions to facilitate early motor development may improve outcomes of this high-risk population.

BACKGROUND The decision to pursue chronic mechanical ventilation involves a complex mix of clinical and social considerations. Understanding the medical indications to pursue tracheostomy would reduce the ambiguity for both providers and families and facilitate focus on appropriate clinical goals. OBJECTIVE To describe potential indications to pursue tracheostomy and chronic mechanical ventilation in infants with severe BPD (sBPD). STUDY DESIGN We surveyed centers participating in the Children's Hospitals Neonatal Consortium to describe their approach to proceed with tracheostomy in infants with sBPD. We requested a single representative response per institution. Question types were fixed form and free text responses. RESULTS The response rate was high (31/34, 91%). Tracheostomy was strongly considered when: airway malacia was present, PCO2 ≥ 76-85 mmHg, FiO2 ≥ 0.60, PEEP ≥ 9-11 cm H2O, respiratory rate ≥ 61-70 breaths/min, PMA ≥ 44 weeks, and weight

Background Early detection of delay or impairment in motor function is important to guide clinical management and inform prognosis during a critical window for the development of motor control in children. The purpose of this study was to investigate the ability of biomechanical measures of early postural control to distinguish infants with future impairment in motor control from their typically developing peers. Methods We recorded postural control from infants lying in supine in several conditions. We compared various center of pressure metrics between infants grouped by birth status (preterm and full term) and by future motor outcome (impaired motor control and typical motor control). Results One of the seven postural control metrics—path length—was consistently different between groups for both group classifications and for the majority of conditions. Conclusions Quantitative measures of early spontaneous infant movement may have promise to distinguish early in life between infants who are at risk for motor impairment or physical disability and those who will demonstrate typical motor control. Our observation that center of pressure path length may be a potential early marker of postural instability and motor control impairment needs further confirmation and further investigation to elucidate the responsible neuromotor mechanisms. Impact The key message of this article is that quantitative measures of infant postural control in supine may have promise to distinguish between infants who will demonstrate future motor impairment and those who will demonstrate typical motor control. One of seven postural control metrics—path length—was consistently different between groups. This metric may be an early marker of postural instability in infants at risk for physical disability.

RATIONALE Aerosolized albuterol is widely used, but its tolerability and efficacy in infants with severe bronchopulmonary dysplasia (sBPD) is not well established. OBJECTIVES To compare the tolerability and efficacy of two dose levels of aerosolized albuterol to saline placebo in infants with sBPD. METHODS Single-center, multiple-crossover trial in 24 ventilated very preterm infants with sBPD. Albuterol (1.25 mg, 2.5 mg) and 3 ml of normal saline were administered every 4 h during separate 24-h treatment periods assigned in random order with a 6-h washout phase between periods. The primary outcome was the absolute change (post and pretherapy) in expiratory flow at 75% of exhalation (EF75). Secondary endpoints were changes in ventilator parameters, vital signs, and heart arrhythmia. RESULTS Average within subject EF75 values improved with each therapy: saline placebo ( + 0.45 L/min ± 2.5, p = .04), 1.25 mg of albuterol ( + 0.70 L/min ± 2.4, p

Neonatal chylothorax (NCTx) and central lymphatic flow disorder (CLFD) are historically challenging neonatal disorders with high morbidity and mortality. METHODS We conducted a retrospective study of 35 neonates with pulmonary lymphatic abnormalities at our institution who underwent lymphatic evaluation between December 2015 and September 2018. Patients with only pulmonary lymphatic perfusion syndrome were classified as NCTx and those with multiple flow abnormalities were classified as CLFD. Demographics, clinical characteristics, and outcomes were compared using t-tests/Wilcoxon rank sum tests and Fisher's exact tests. RESULTS All 35 patients had intranodal MR lymphangiography and 14 (40%) also had conventional fluoroscopic lymphangiography. Fifteen (42.8%) patients were diagnosed with NCTx and 20 (57.1%) were diagnosed with CLFD. Thirty-four (97.1%) patients had pleural effusions. None of the NCTx group had ascites, anasarca, or dermal backflow compared to 17 (85%) (p

Bronchopulmonary dysplasia is a common disease of prematurity that presents along a wide spectrum of disease severity. Infants with high severity require prolonged hospitalizations and benefit from multidisciplinary care. We describe our approach to the evaluation of infants with severe bronchopulmonary dysplasia. Important considerations include the phenotypic heterogeneity in clinical presentation that necessitates individualized care, the common presence of comorbidities and importance of a comprehensive multisystem evaluation, and the value of applying a chronic care model that prioritizes long-term respiratory and neurodevelopmental goals. Key features of the history, physical examination, and diagnostic studies are discussed with these considerations in mind.

Bronchopulmonary dysplasia (BPD) is an acquired, developmental chronic lung disease that is a consequence of premature birth. In the most severe form of the disease, infants may require prolonged periods of positive pressure ventilation. BPD is a heterogeneous disease with lung mechanics that differ from those in respiratory distress syndrome; strategies to manage the respiratory support in infants with severe BPD should take this into consideration. When caring for these infants, practitioners need to shift from the acute care ventilation strategies that use frequent blood gases and support adjustments designed to minimize exposure to positive pressure. Infants with severe BPD benefit from a chronic care model that uses less frequent ventilator adjustments and provides the level of positive support that will achieve the longer-term goal of ongoing lung growth and repair.

Key Points Question What are the care practices and outcomes for very preterm infants in Chinese neonatal intensive care units? Findings In this cohort study of 9552 very preterm infants from 57 tertiary neonatal intensive care units throughout China in 2019, 86% received complete care, among whom 95% survived and 57% survived without major morbidities. Only 76% of the infants received antenatal corticosteroids, and 12% of the infants received delivery room continuous positive airway pressure. Meaning The findings of this study suggest that survival and survival without major morbidity of very preterm infants in Chinese neonatal intensive care units remain lower than in high-income countries and clinical quality improvement as well as systems and health services reorganization are needed to improve outcomes., Importance The Chinese Neonatal Network was established in 2018 and maintains a standardized national clinical database of very preterm or very low-birth-weight infants in tertiary neonatal intensive care units (NICUs) throughout China. National-level data on outcomes and care practices of very preterm infants (VPIs) in China are lacking. Objective To assess the care practices in NICUs and outcomes among VPIs in China. Design, Setting, and Participants A cohort study was conducted comprising 57 tertiary hospitals from 25 provinces throughout China. All infants with gestational age (GA) less than 32 weeks who were admitted to the 57 NICUs between January 1 and December 31, 2019, were included. Main Outcomes and Measures Care practices, morbidities, and survival were the primary outcomes of the study. Major morbidities included bronchopulmonary dysplasia, severe intraventricular hemorrhage (grade ≥3) and/or periventricular leukomalacia, necrotizing enterocolitis (stage ≥2), sepsis, and severe retinopathy of prematurity (stage ≥3). Results A total of 9552 VPIs were included, with mean (SD) GA of 29.5 (1.7) weeks and mean (SD) birth weight of 1321 (321) g; 5404 infants (56.6%) were male. Antenatal corticosteroids were used in 75.6% (6505 of 8601) of VPIs, and 54.8% (5211 of 9503)were born through cesarean delivery. In the delivery room, 12.1% of VPIs received continuous positive airway pressure and 26.7% (2378 or 8923) were intubated. Surfactant was prescribed for 52.7% of the infants, and postnatal dexamethasone was prescribed to 9.5% (636 of 6675) of the infants. A total of 85.5% (8171) of the infants received complete care, and 14.5% (1381) were discharged against medical advice. The incidences of the major morbidities were bronchopulmonary dysplasia, 29.2% (2379 of 8148); severe intraventricular hemorrhage and/or periventricular leukomalacia, 10.4% (745 of 7189); necrotizing enterocolitis, 4.9% (403 of 8171 ); sepsis, 9.4% (764 of 8171); and severe retinopathy of prematurity, 4.3% (296 of 6851) among infants who received complete care. Among VPIs with complete care, 95.4% (7792 of 8171) survived: 65.6% (155 of 236) at 25 weeks’ or less GA, 89.0% (880 of 988) at 26 to 27 weeks’ GA, 94.9% (2635 of 2755)at 28 to 29 weeks’ GA, and 98.3% (4122 of 4192) at 30 to 31 weeks’ GA. Only 57.2% (4677 of 8171) of infants survived without major morbidity: 10.5% (25 of 236) at 25 weeks’ or less GA, 26.8% (48 of 179) at 26 to 27 weeks’ GA, 51.1% (1409 of 2755) at 28 to 29 weeks’ GA, and 69.3% (2904 of 4192) at 30 to 31 weeks’ GA. Among all infants admitted, the survival rate was 87.6% (8370 of 9552)and survival without major morbidities was 51.8% (4947 of 9552). Conclusions and Relevance The findings of this study suggest that survival and survival without major morbidity of VPIs in Chinese NICUs have improved but remain lower than in high-income countries. Comprehensive and targeted quality improvement efforts are needed to provide complete care for all VPIs, optimize obstetrical and neonatal care practices, and improve outcomes., This cohort study evaluates the care practices used for as well as the survival and major morbidities among very preterm infants hospitalized in neonatal intensive care units in China.

Partial liquid ventilation is proposed as an alternative ventilation strategy to reduce surface tension, increase alveolar recruitment, and decrease inflammation. Studied in acute respiratory distress and other indications, liquid ventilation is being revisited for infants with bronchopulmonary dysplasia. Perfluorooctyl bromide used for liquid ventilation is radiopaque, allowing radiographic visualization of lung liquid ventilation patterns that may provide additional insight into pulmonary pathophysiology. Current protocols utilize reduced liquid dosing, resulting in unique imaging features. We discuss optimal radiographic technique and report initial ultrasound evaluation results. With renewed interest in partial liquid ventilation, it may be helpful for pediatric radiologists to familiarize themselves with the clinical use and radiographic appearance of liquid ventilation material.

Rationale Infants with severe bronchopulmonary dysplasia (sBPD) and airway obstruction may develop dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEPi ), which impairs patient/ventilator synchrony. Objectives To determine if PEEPi is present in infants with sBPD during spontaneous breathing and if adjusting ventilator PEEP improves patient/ventilator synchrony and comfort. Methods Interventional study in infants with sBPD. PEEPi measured by esophageal pressure (Pes) and pneumotachometer, during pressure-supported breaths. PEEP i defined as the difference between Pes at start of the inspiratory effort minus Pes at onset of inspiratory flow. The set PEEP was adjusted to minimize PEEP i . "Best PEEP" was the setting with minimal wasted efforts (WE), an inspiratory effort seen on the Pes waveform without a corresponding ventilator breath. FiO 2 and SpO 2 measured pre- and post-PEEP adjustment. Sedation requirements evaluated 72 hours preprocedure and postprocedure. Results Twelve infants were assessed (gestational age, 24.9 ± 1.4 weeks; study age, 48.8 ± 1.5 weeks, postmenstrual age). Mean baseline ventilator PEEP was 16.4 cm H2 O (14-20 cm H 2 O). Eight infants required an increase, one, a reduction, and three, no change in the set PEEP. For the eight infants requiring an increase in set PEEP, there was an 18.9% reduction in WE and a reduction in FiO 2 (0.084 ± 0.058) requirements in the subsequent 24 hours. Conditional sedation was reduced in five infants postprocedure. No adverse events occurred during testing. Conclusion PEEPi is measurable in infants with sBPD with concurrent esophageal manometry and flow-time tracings without the need for pharmacological paralysis. In those with PEEP i , increasing ventilator PEEP to offset PEEP i improves synchrony.

Objective To assess parents' views of their children's health-related quality of life (HRQoL) and the association between neonatal morbidities and HRQoL in children with severe bronchopulmonary dysplasia (BPD) who survived to 18-36 months of corrected age. Study Design Study population included infants born Results Seventy children (67% male, gestational age 26.1 ± 2.0 weeks, and birth weight 797 ± 318g) were enrolled at 27.1 ± 5.8 months of corrected age. Mean PHY-QoL and PS-QoL were 78.0 ± 21.9 and 75.3 ± 17.9, respectively, both significantly lower than reported means for term and preterm cohorts, with the exception of emotional QoL. Adjusted postnatal composite morbidity score was cumulatively associated with poorer PHY-QoL (P = .002) and poorer PS-QoL (P = .015). Presence of each additional neonatal morbidity was associated with a 4.4-point decrease in PHY-QoL and 2.8-point decrease in PS-QoL. Conclusions In this cohort, parental perceived HRQoL for their child with severe BPD was lower than expected for term and preterm populations. Neonatal morbidities had an additive association with poorer parental assessment of PHY-QoL and PS-QoL. These findings may aid in care of children with severe BPD and their families, both in the intensive care nursery and postdischarge.

Background: Premature infants with severe bronchopulmonary dysplasia (sBPD) are at risk of pulmonary hypertension (PH). Serum brain natriuretic peptide (BNP) is used to predict disease severity in adult PH. Its diagnostic utility in sBPD-associated PH is unknown. Objective: The aim of this paper was to determine the accuracy of BNP, against echocardiogram (echo), to diagnose PH in infants born Methods: We conducted a retrospective cohort study of all infants with sBPD with an echo and BNP within a 24-h period, at ≥36 weeks postmenstrual age. PH was defined as: right ventricular pressure >½ systemic blood pressure estimated from tricuspid regurgitant jet or patent ductus arteriosus (PDA) velocity, bidirectional or right-to left-PDA, and/or flat/bowing ventricular septum at end-systole. Receiver-operating characteristic (ROC) curves were constructed to test the diagnostic accuracy of BNP. Results:Of 128 infants, 68 (53%) had echo evidence of PH. BNP was higher among the infants with PH (median [interquartile range]: 127 pg/mL [39–290] vs. 35 [20–76], p < 0.001). The area under the ROC curve for diagnosing PH using BNP was 0.74 (95% CI 0.66–0.83). At an optimal cutpoint of 130 pg/mL, BNP correctly classified the presence or absence of PH in 70% of the infants (specificity: 92, sensitivity: 50%). Conclusions: BNP, relative to concurrent echo, demonstrated moderate accuracy for diagnosing PH in this cohort of preterm infants with sBPD. BNP may help rule in PH in this population but has low utility to rule out the disease.

To describe the findings, resulting changes in management, and safety profile of flexible bronchoscopy in the neonates with severe bronchopulmonary dysplasia. This was a retrospective case series of twenty-seven neonates with severe bronchopulmonary dysplasia who underwent flexible bronchoscopy in the neonatal intensive care unit. Flexible bronchoscopy revealed airway pathology in 20/27 (74%) patients. Tracheomalacia 13/27 (48%), bronchomalacia 11/27 (40.7%), and airway edema 13/27 (48%) were the most common findings. Bronchoalveolar lavage (BAL) was performed in 17 patients. BAL culture revealed a microorganism in 12/17 (70.5%) cases. Findings from bronchoscopy resulted in change in clinical management in 17/27 (63%) patients. Common interventions included initiation of antibiotics (37%) and treatment of tracheobronchomalacia with bethanechol (22.2%), atrovent (18.5%), and PEEP titration (18.5%). Bronchoscopy was performed without significant complication in 26/27 (97%) patients. Flexible bronchoscopy can be a safe and useful tool for the management of neonates with severe bronchopulmonary dysplasia.

OBJECTIVES: Immunizations provide important protection from serious childhood illnesses. Infant chronic lung disease (CLD) is a serious complication of prematurity and predisposes premature infants to respiratory morbidity, rehospitalization, and mortality. This high-risk group is especially vulnerable to infections, such as invasive pneumococcal disease, influenza, and bronchiolitis. Our purpose for this project was to increase 2-, 4-, and 6-month immunization rates in eligible infants with CLD in the NICU by 30% through December 2016. METHODS: A multidisciplinary team developed weekly targeted rounds to identify eligible patients with outstanding immunizations. Exclusion criteria included the following: (1) a fraction of inspired oxygen requirement of >80%, (2) pulmonary hypertensive crisis, (3) positive blood culture results or if within 48 hours of a sepsis evaluation, (4) if within 5 days of a surgical or interventional procedure, (5) receiving steroid treatment (not including a physiologic hydrocortisone dose for adrenal insufficiency), (6) a CLD team consensus of contraindication, and (7) parental refusal. RESULTS: The project managed 60 patients from March 2016 to December 2016. Immunization of eligible patients increased from 44% to 75% and was sustained for the next 6 months. The average number of days from admission to immunization record review decreased from 71 days at baseline to 27 days. CONCLUSIONS: The implementation of (1) an in-hospital immunization record review, (2) an e-mail reminder, (3) a weekly multidisciplinary eligibility discussion, and (4) an updated rounding tool was successful in increasing and sustaining immunization rates in this population of infants with CLD. The multidisciplinary CLD meeting was a novel opportunity to discuss immunization eligibility and safety monitoring.

IntroductionDespite the increase in the survival rate of high-risk infants (HRIs) worldwide, the prevalence of motor and neurodevelopmental sequelae in such newborns has not shown concomitant improvement. Meanwhile, there are few cohorts that explore factors related to the development of HRIs in China. Therefore, the Guangzhou High-Risk Infant Cohort (GHRIC) has been designed to examine the complex relationships among a myriad of factors influencing growth and development in such children.Methods and analysisThe GHRIC study is a prospective cohort study that by the year 2023 will enrol an estimated total of 3000 HRIs from Guangzhou Women and Children’s Medical Center (GWCMC) in Guangzhou, China. This study is designed to assess the growth and cognitive characteristics of HRIs and the risk factors affecting their development and prognoses. Data on risk factors, neurodevelopmental and cognitive-function evaluations, laboratory results, and specimens will be collected and analysed. Information on perinatal and clinical interventions for these infants will also be recorded during regular follow-up visits until age 6.Ethics and disseminationThe protocol for this study has been approved by the Research Ethics Committee of GWCMC, which accepted responsibility for supervising all of the aspects of the study (No. 2017102712). Study outcomes will be disseminated through conference presentations, peer-reviewed publications, the Internet and social media.Trial registration numberChiCTR-EOC-17013236

AIM: This review examined how applicable national and regional clinical practice guidelines and recommendations for managing neonates born to mothers with COVID-19 mothers were to the evolving pandemic. METHODS: A systematic search and review identified 20 guidelines and recommendations that had been published by May 25, 2020. We analysed documents from 17 countries: Australia, Brazil, Canada, China, France, India, Italy, Japan, Saudi Arabia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, the UK and the United States. RESULTS: The documents were based on expert consensus with limited evidence and were of variable, low methodological rigour. Most did not provide recommendations for delivery methods or managing symptomatic infants. None provided recommendations for post-discharge assimilation of potentially infected infants into the community. The majority encouraged keeping mothers and infants together, subject to infection control measures, but one-third recommended separation. Although breastfeeding or using breastmilk was widely encouraged, two countries specifically prohibited this. CONCLUSION: The guidelines and recommendations for managing infants affected by COVID-19 were of low, variable quality and may be unsustainable. It is important that transmission risks are not increased when new information is incorporated into clinical recommendations. Practice guidelines should emphasise the extent of uncertainty and clearly define gaps in the evidence.

* Abbreviations: ARDS: : acute respiratory distress syndrome BPD: : bronchopulmonary dysplasia CHOP: : Children’s Hospital of Philadelphia ECLS: : extracorporeal life support FDA: : Food and Drug Administration FRC: : functional residual capacity HFOV: : high-frequency oscillatory ventilation PEEP: : positive end-expiratory pressure PFC: : perfluorocarbon PFOB: : perfluorooctyl bromide PLV: : partial liquid ventilation RDS: : respiratory distress syndrome TLV: : total (tidal) liquid ventilation Survival rates in extremely premature infants are increasing as are rates of bronchopulmonary dysplasia. Current therapeutic options are not sufficient to prevent or treat bronchopulmonary dysplasia in many infants. This presents a large cost, both human and economic. Perfluorocarbon liquids have been studied since the 1960s for various biomedical applications. After some promising studies in the 1990s, work in this field was halted. Despite considerable attention, including significant amounts of published data, the temporal gap has seen a generation of physicians who may not know about this potentially valuable therapy. This article will reintroduce partial liquid ventilation, a promising therapeutic option in acute and chronically ill infants, to clinicians by examining the history and presenting new data. After completing this article, readers should be able to: 1. Identify the physiologic function of perfluorocarbon liquid in the human lung. 2. Describe the historical development of partial liquid ventilation and contextualize the published literature. 3. Explain the limitations of partial liquid ventilation and roadblocks in the past. In their 1962 article entitled, “Of mice as fish,” Kylstra and colleagues wrote with excitement about the implications of a newfound mode of ventilation. In liquid ventilation using oxygenated saline solutions, these investigators saw a sort of reverse engineering of evolution—mammals regressing to their supposed piscine origins. Kylstra et al envisioned a world in which pool water, titrated to have an adequate saline concentration, would allow for more efficacious resuscitation from drowning. (1) In its most essential form, liquid ventilation involves filling the lungs of an animal with some kind of liquid. That liquid, at varying doses, may be cycled in and out of the lungs with the assistance of a ventilator. In 1966, Clark and Gollan first described the use of perfluorocarbons (PFCs) in liquid ventilation toward a similar end as did Kylstra and colleagues—undersea survival and …

We report epidemiological and clinical investigations on ten pediatric SARS-CoV-2 infection cases confirmed by real-time reverse transcription PCR assay of SARS-CoV-2 RNA. Symptoms in these cases were nonspecific and no children required respiratory support or intensive care. Chest X-rays lacked definite signs of pneumonia, a defining feature of the infection in adult cases. Notably, eight children persistently tested positive on rectal swabs even after nasopharyngeal testing was negative, raising the possibility of fecal-oral transmission.

Pneumothorax (PTX) represents accumulation of the air in the pleural space. A large or tension pneumothorax can collapse the lung and cause hemodynamic compromise, a life-threatening disorder. Traditionally, neonatal pneumothorax diagnosis has been based on clinical images, auscultation, transillumination, and chest X-ray findings. This approach may potentially lead to a delay in both diagnosis and treatment. The use of lung US in diagnosis of PTX together with US-guided thoracentesis results in earlier and more precise management. The recommendations presented in this publication are aimed at improving the application of lung US in guiding neonatal PTX diagnosis and management.

Background: Very low birth weight premature (VLBW) infants with bronchopulmonary dysplasia (BPD) often need prolonged respiratory support, which is associated with worse outcomes. The application of neurally adjusted ventilatory assist ventilation (NAVA) in infants with BPD has rarely been reported. This study investigated whether NAVA is safe and can reduce the duration respiratory support in VLBW premature infants with established or evolving BPD.Methods: This retrospective matched-cohort study included patients admitted to our NICU between April 2017 to April 2019 who were born at 0.05). However, NAVA was well tolerated and there was a decrease in the need of sedation (p = 0.012) after switching to NAVA.Conclusion: NAVA, when used as a sequel mode of ventilation, in premature neonates

Background: COVID-19 has spread to virtually all countries, and is still increasing rapidly However, pediatric cases are uncommon and their epidemiological and

OBJECTIVES: This study tested the hypothesis that longer duration of any type of respiratory support is associated with an increased rate of death or neurodevelopmental impairment (NDI) at 18–22 months. METHODS: Retrospective cohort study using the Generic Database of NICHD Neonatal Research Network from 2006 to 2010. Infants were born at

Objective We compared the accuracy of serum intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), and phosphate (phos) levels for diagnosing severe metabolic bone disease (MBD) in very low-birth-weight (VLBW) infants with severe bronchopulmonary dysplasia (BPD). Study Design Retrospective analysis of VLBW infants with severe BPD admitted between 2010 and 2012 and with ≥ 1 iPTH, ALP, and phos level collected within a similar 72-hour period. MBD severity was classified by serial radiography. Results Laboratory values were available for 65 infants, of whom 24 (36.9%) developed severe MBD. A maximum ALP > 660 IU/L was the most accurate for diagnosing severe MBD (area under the curve: 88.4%; 95% confidence interval [CI]: 77.2–94.5%). Maximum iPTH was the least accurate (optimal cut point > 130 pg/mL; area under the curve: 70.5%; 95% CI: 58.2–81.4). Conclusion Maximum ALP was more accurate than iPTH or phos for diagnosing severe MBD among preterm infants with severe BPD.

Objective To determine the relationship between interventricular septal position (SP) and right ventricular systolic pressure (RVSP) and mortality in infants with severe BPD (sBPD). Study design Infants with sBPD in the Children’s Hospitals Neonatal Database who had echocardiograms 34–44 weeks’ postmenstrual age (PMA) were included. SP and RVSP were categorized normal, abnormal (flattened/bowed SP or RVSP > 40 mmHg) or missing. Results Of 1157 infants, 115 infants (10%) died. Abnormal SP or RVSP increased mortality (SP 19% vs. 8% normal/missing, RVSP 20% vs. 9% normal/missing, both p

To identify the number of cumulative medication exposures and most frequently used medications in infants with severe BPD. We performed a retrospective cohort study in infants with severe BPD admitted to United States children’s hospitals. We measured cumulative medication exposures in individual subjects and between-center variation after adjustment for infant characteristics. We then identified the specific medications and therapeutic classes with the highest rates of use. In 3252 subjects across 43 hospitals, we identified a median (interquartile range) of 30 (17–45) cumulative medication exposures per infant. The adjusted mean number of medication exposures varied between centers (p

Ultrasound is a safe bedside imaging tool that obviates the use of ionizing radiation diagnostic procedures. Due to its convenience, the lung ultrasound has received increasing attention from neonatal physicians. Nevertheless, clear reference standards and guideline limits are needed for accurate application of this diagnostic modality. This document aims to summarize expert opinions and to provide precise guidance to help facilitate the use of the lung ultrasound in the diagnosis of neonatal lung diseases.

ObjectiveCompare rates of hypoxaemia during transpyloric and gastric feedings in very preterm infants with severe bronchopulmonary dysplasia.DesignN-of-1 multiple crossover trials with individual patient and pooled data analyses.SettingLevel IV intensive care nursery.PatientsInfants receiving positive airway pressure between 36 and 55 weeks postmenstrual age were enrolled between December 2014–July 2016.InterventionN-of-1 trial consisting of two blocks, each with a 4-day gastric and 4-day transpyloric feeding period assigned in random order.Main outcome measuresThe primary outcome was the frequency of daily intermittent hypoxaemic events (SpO2≤80% lasting 10–180 s). Secondary outcomes included the daily proportion of time with an SpO2≤80% and mean daily fraction of inspired oxygen.ResultsOf 15 infants, 13 completed the trial and 2 stopped early for transient worsening in respiratory status during gastric feedings. In the intention-to-treat analyses, transpyloric feedings resulted in increased rates of intermittent hypoxaemia in five infants, greater time per day in hypoxaemia in three infants and more supplemental oxygen use in three infants. One infant received more supplemental oxygen during gastric feedings. The remaining study outcomes were similar between the feeding routes in all other infants. Pooling all data, transpyloric feedings resulted in a higher frequency of intermittent hypoxaemic events (median 7.5/day (IQR 1–23.5) vs 3/day (1–11); adjusted incidence rate ratio 1.8, 95% CI 1.3 to 2.5) and a greater proportion of daily hypoxaemia time (median 0.8% (IQR 0.1–2.3) vs 0.4% (0.07–1.8); adjusted mean difference 1.6, 95% CI 1.1 to 2.5).ConclusionsTranspyloric compared with gastric feedings modestly increased rates of hypoxaemia among study participants.Trial registration numberNCT02142621

Over the past four decades, advances in neonatal intensive care have led to the survival of smaller and more immature infants. The improved survival of very low birth weight infants is associated with long term respiratory morbidity, most frequently in the form of bronchopulmonary dysplasia. In this review, we will discuss the pathogenesis, risk factor as well as management of commonly seen acquired airway disorders associated with prematurity, prolonged intubation and ventilation.

Optimal nutrition and growth in patients with severe, established bronchopulmonary dysplasia are complex and require an understanding of the factors and challenges that affect this population. Most publications have reported weight gain as the primary outcome because of ease of measurement, accuracy, and repeatability. There is, however, increasing evidence that linear growth is better correlated with long-term development and pulmonary outcomes. In addition, factors such as stress, inflammation, respiratory support and stability, and medication exposures have a direct influence on achieving nutritional success in infants with severe bronchopulmonary dysplasia. This article reviews concepts related to these challenges and provides recommendations for achieving successful nutrition in this population.

Pulmonary vein stenosis (PVS) is a rare condition that has been linked to prematurity and congenital heart disease (CHD). Despite these associations, treatment options are limited and outcomes are guarded. We investigated differences in PVS outcomes based on the presence of CHD and prematurity, and risk factors for mortality or lung transplantation in PVS. Single-center retrospective cohort study of patients diagnosed with PVS between January 2005 and May 2016 and identified by ICD codes with chart validation. Cox proportional hazard models assessed risk factors for the composite outcome of mortality or lung transplantation. Ninety-three patients with PVS were identified: 65 (70%) had significant CHD, 32 (34%) were premature, and 14 (15%) were premature with CHD. Sixty-five (70%) underwent a PVS intervention and 42 (46%) underwent ≥2 interventions. Twenty-five subjects (27%) died or underwent lung transplant 5.8 months (interquartile range [IQR] 1.1, 15.3) after diagnosis. There was no difference in age at diagnosis or mortality based on presence of CHD or prematurity. PVS diagnosis before age 6 months and greater than 1 pulmonary vein affected at diagnosis were associated with higher mortality (hazards ratio [HR] 3.4 (95% confidence interval 1.5, 7.5), P = 0.003, and HR 2.1 per additional vein affected (95% confidence interval 1.3, 3.4), P = 0.004, respectively). Survival in children with PVS is poor, independent of underlying CHD or prematurity. Younger age and greater number of veins affected at diagnosis are risk factors for worse outcome. Understanding causal mechanisms and development of treatment strategies are necessary to improve outcomes.

OBJECTIVES To examine growth, sedation needs, and participation in developmental activities before and after tracheostomy among infants with severe bronchopulmonary dysplasia. METHODS Retrospective analysis of infants born at

Despite the advance in neonatal care over the past few decades, preventing preterm infants with respiratory distress syndrome progress to bronchopulmonary dysplasia remained challenging. In this review, we will discuss the respiratory support strategies in preterm infants with RDS evolving into BPD based on the changes in pulmonary mechanics and pathophysiology as well as currently available evidence.

Background: Very low birth weight (VLBW; BW ≤1500g) infants with severe BPD may require prolonged mechanical ventilation. While tracheostomy in these patients is associated with adverse neurodevelopmental outcomes, causality is difficult to show and tracheostomy placement may have other benefits in addition to provide a stable airway in this population. Objective: To evaluate growth indices and participation in developmental activities before and after tracheostomy in VLBW infants with severe BPD. Method: We conducted a retrospective analysis of VLBW infants born at ≤32 week gestation who were …

Background: Despite advances in neonatal care, management of infants with severe bronchopulmonary dysplasia (sBPD) remains difficult. Objective: To describe the multidisciplinary care model and five-year outcomes of the Newborn and Infant Chronic Lung Disease (NeoCLD) Program at The Children's Hospital Of Philadelphia (CHOP). Methods/Results: The CHOP NeoCLD program was established in 2010 to improve the care of infants with extremely severe BPD. Given the chronic and multi-system involvement nature of this disease, we took a complex care multidisciplinary …

Objective Nonrespiratory comorbidities are common among preterm infants with severe bronchopulmonary dysplasia (BPD) referred to tertiary perinatal centers. We evaluated the incidence, severity, and risk factors for metabolic bone disease (MBD) in this population. Study Design We conducted a retrospective cohort study of all infants born ≤ 1,500 g who were diagnosed with severe BPD in our single, tertiary referral center between September 2010 and October 2012. MBD severity was classified by serial radiography. Results Among the 83 infants diagnosed with severe BPD, 26 (31%) developed severe MBD (rickets). Male gender and lower gestational age and birth weight were associated with increased odds of severe MBD. After adjustment for these potential confounders, cytomegalovirus infection, postnatal growth restriction, surgical necrotizing enterocolitis, and blood culture confirmed sepsis were associated with increased odds of severe MBD. The cumulative duration of therapy with furosemide, hydrocortisone, and prednisolone each correlated with significantly greater probability of severe MBD. Conclusions Severe MBD was common in this referral-based cohort with severe BPD. The high incidence in this population is likely explained by the coexistence of multiple exposures and comorbidities associated with bone demineralization.

Despite improvements in survival of preterm infants, bronchopulmonary dysplasia (BPD) remains a persistent morbidity. The incidence, clinical course, and current management of severe BPD (sBPD) remain to be defined. To address these knowledge gaps, a multicenter collaborative was formed to improve outcomes in this population.We performed a "snapshot" in eight neonatal intensive care units (NICUs) on December 17, 2013. A standardized clinical data form for each inpatient born at 32 weeks was completed and collated centrally for analysis. sBPD was defined as receiving ≥ 30% supplemental oxygen and/or receiving positive pressure ventilation at 36 weeks postmenstrual age (PMA).Of a total census of 710 inpatients, 351 infants were born at 32 weeks and 128 of those (36.5%) met criteria for sBPD. The point prevalence of sBPD varied between centers (11-58%; p 0.001). Among infants with sBPD there was a variation among centers in the use of mechanical ventilation at 28 days of life (p 0.001) and at 36 weeks PMA (p = 0.001). We observed differences in the use of diuretics (p = 0.018), inhaled corticosteroids (p 0.001), and inhaled β-agonists (p 0.001).The high point prevalence of sBPD and variable management among NICUs emphasizes the lack of evidence in guiding optimal care to improve long-term outcomes of this high-risk, understudied population.

Tracheobronchomalacia is a common comorbidity in neonates with bronchopulmonary dysplasia. However, the effect of tracheobronchomalacia on the clinical course of bronchopulmonary dysplasia is not well-understood.We sought to assess the impact of tracheobronchomalacia on outcomes in neonates with bronchopulmonary dysplasia in a large, multi-center cohort.We preformed a cohort study of 974 neonates with bronchopulmonary dysplasia admitted to 27 neonatal intensive care units participating in the Children's Hospital Neonatal Database who had undergone bronchoscopy. In hospital morbidity for neonates with bronchopulmonary dysplasia and tracheobronchomalacia (N=353, 36.2%) was compared to those without tracheobronchomalacia (N=621, 63.8%) using mixed-effects multivariate regression.Neonates with tracheobronchomalacia and bronchopulmonary dysplasia had more comorbidities, such as gastroesophageal reflux (OR=1.65, 95%CI 1.23- 2.29, P=0.001) and pneumonia (OR=1.68, 95%CI 1.21-2.33, P=0.002) and more commonly required surgeries such as tracheostomy (OR=1.55, 95%CI 1.15-2.11, P=0.005) and gastrostomy (OR=1.38, 95%CI 1.03-1.85, P=0.03) compared with those without tracheobronchomalacia. Neonates with tracheobronchomalacia were hospitalitized (118 ± 93 vs 105 ± 83 days, P=0.02) and ventilated (83.1 ± 91.1 vs 67.2 ± 71.9 days, P=0.003) longer than those without tracheobronchomalacia. Upon discharge, neonates with tracheobronchomalacia and BPD were more likely to be mechanically ventilated (OR=1.37, 95CI 1.01-1.87 P=0.045) and possibly less likely to receive oral nutrition (OR=0.69, 95%CI 0.47-1.01, P=0.058).Tracheobronchomalacia is common in neonates with bronchopulmonary dysplasia who undergo bronchoscopy and is associated with longer and more complicated hospitalizations.

Gastroesophageal reflux may exacerbate lung disease in infants with bronchopulmonary dysplasia (BPD). Anti-reflux surgery may therefore reduce the severity of this disease in some infants. We report a retrospective series of 22 infants with severe BPD who underwent anti-reflux surgery. Our experience indicates that these procedures can be safely performed in this population and that early post-operative initiation of gastric feeds is well tolerated. Modest post-operative reductions in required oxygen and median respiratory rate were observed.

To estimate the risk of death or tracheostomy placement (D/T) in infants with severe bronchopulmonary dysplasia (sBPD) born32 weeks' gestation referred to regional neonatal intensive care units.We conducted a retrospective cohort study in infants born32 weeks' gestation with sBPD in 2010-2011, using the Children's Hospital Neonatal Database. sBPD was defined as the need for FiO2 ⩾ 0.3, nasal cannula support2 l min(-1) or positive pressure at 36 weeks' post menstrual age. The primary outcome was D/T before discharge. Predictors associated with D/T in bivariable analyses (P0.2) were used to develop a multivariable logistic regression equation using 80% of the cohort. This equation was validated in the remaining 20% of infants.Of 793 eligible patients, the mean gestational age was 26 weeks' and the median age at referral was 6.4 weeks. D/T occurred in 20% of infants. Multivariable analysis showed that later gestational age at birth, later age at referral along with pulmonary management as the primary reason for referral, mechanical ventilation at the time of referral, clinically diagnosed pulmonary hypertension, systemic corticosteroids after referral and occurrence of a bloodstream infection after referral were each associated with D/T. The model performed well with validation (area under curve 0.86, goodness-of-fit χ(2), P = 0.66).Seven clinical variables predicted D/T in this large, contemporary cohort with sBPD. These results can be used to inform clinicians who counsel families of affected infants and to assist in the design of future prospective trials.

To develop and test a decision aid for counseling parents of children with bronchopulmonary dysplasia (BPD).Local problem:Parental education about complex conditions is not standardized and communication and understanding may not be adequate.Semi-structured interviews were conducted with 33 neonatal clinicians and 12 parents of children with BPD using a qualitative research design. The interviews were used to identify education topics that were felt to be important in BPD education. These topics were then used to create a visual decision aid to be used in counseling sessions with parents. The decision aid was then used in mock counseling sessions with 15 'experienced' participants and 7 'naïve' participants to assess its efficacy. The participants completed a pre and post test to assess change in knowledge as well as an 11-question Likert style acceptability survey.Implementation of a decision aid while educating parents about BPD.Topics identified during the interviews were used to create eight educational cards which included pictures, pictographs and statistics. Overall, participants thought the decision aid contained an appropriate amount of information, were easy to understand and improved their knowledge about BPD. Testing demonstrated a significant increase in knowledge in both the 'experienced' (P0.0001) and 'naïve' group (P=0.0064).A decision aid for parents of children with BPD may improve understanding of the condition and help facilitate communication between parents and doctors.

Efficient gene transfer is a critical goal in retroviral transduction. Several peptides capable of forming amyloid fibrils, such as the 39-residue semen-derived infection-enhancing peptide (SEVI), have demonstrated the ability to boost retroviral gene delivery. Here, a 13-residue peptide P13 (Ac-(671) NWFDITNWLWYIK(683)) derived from the membrane-proximal external region of the human immunodeficiency virus type 1 (HIV-1) gp41 transmembrane protein, together with its 16-residue peptide derivative (P16) were found to enhance HIV-1 infection significantly. Both peptides, P13 and P16, could form amyloid fibril structures to potently enhance HIV-1 infectivity. Further investigations showed that both aromatic Trp residues and cationic Lys residues contributed to the enhancement of HIV-1 infection by these two active peptides. P16 could more effectively augment HIV-1 YU-2 infection than SEVI, implying its potential applications as a tool in the lab to improve gene transfer rates.

Objectives To assess the effect of pulmonary hypertension on neonatal intensive care unit mortality and hospital readmission through 1 year of corrected age in a large multicenter cohort of infants with severe bronchopulmonary dysplasia. Study design This was a multicenter, retrospective cohort study of 1677 infants born Results Pulmonary hypertension occurred in 370 out of 1677 (22%) infants. During the neonatal admission, pulmonary hypertension was associated with mortality (OR 3.15, 95% CI 2.10-4.73, P Conclusions Infants with severe bronchopulmonary dysplasia-associated pulmonary hypertension have increased morbidity and mortality through 1 year of corrected age. This highlights the need for improved diagnostic practices and prospective studies evaluating treatments for this high-risk population.

Congenital tuberculosis (CTB) due to maternal genitourinary (GU) TB infection is a rare occurrence, as infection of the genital tract in women generally leads to infertility. Increasing availability of assisted reproductive technology creates the potential for CTB to emerge as a significant problem. We describe five infants (two sets of twins and a singleton birth) conceived by in vitro fertilization who developed CTB. All five infants were born to mothers who had immigrated to the United States from India and none had GU TB diagnosed before the birth of their infected infants.

Eliciting a broadly neutralizing antibody response against the HIV-1 membrane-proximal external region (MPER) mimicking the activity of 4E10 and 2F5 monoclonal antibodies remains a major challenge. In this study, two novel tetra-branched peptide immunogens, 4E10- and 2F5-MAP4, were designed and synthesized using a MAP system. Guinea pigs were immunized with either of these two synthetic immunogens emulsified in an oil-phase adjuvant at 3-week intervals. After four immunizations, epitope-specific antibody responses were induced successfully, and moderate neutralizing activities against tier 1 (clades B, BC, AE) and tier 2 (clade C) HIV-1 pseudoviruses were detectable in unfractionated sera and purified IgGs. The synthetic gp41 membrane-proximal external region peptide mimetics, 4E10- and 2F5-MAP4, assisted by an appropriate adjuvant, are promising prophylactic vaccine candidates potentially capable of eliciting broadly neutralizing antibody responses against HIV-1. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.

Objective Bacterial colonization of the airway may contribute to the development of bronchopulmonary dysplasia. Whether airway colonization increases risk for later adverse respiratory outcomes is less clear. We described tracheal aspirate culture results obtained from preterm infants receiving mechanical ventilation at 36 weeks postmenstrual age (PMA) and evaluated the association between bacteria type and the risk for prolonged supplemental oxygen use. Study Design We conducted a retrospective, single-center cohort study comparing infants (1) with and without a tracheal aspirate culture that grew a Gram-negative rod (GNR) and (2) with and without a culture that grew a Gram-positive cocci (GPC). Results Among 121 infants, 65 (53.7%) and 51 (42.2%) had a tracheal aspirate culture that grew a potentially pathogenic GNR and GPC prior to 36 weeks PMA, respectively. GNR were associated with increased risk for death or use of supplemental oxygen at discharge (adjusted odds ratio [aOR], 6.2; 95% confidence interval [CI], 1.8–21.1), and use of supplemental oxygen at discharge among survivors (aOR, 5.5; 95% CI, 1.6–19.0). GPC did not affect the risk for any study outcomes. Conclusion GNR but not GPC in the airways of preterm infants receiving mechanical ventilation at 36 weeks PMA is associated with increased risk for prolonged supplemental oxygen use.

The Avalon Elite Bi-caval Dual Lumen cannula was designed for placement in the right internal jugular vein for veno-venous double lumen extracorporeal membrane oxygenation (VVDL ECMO). Despite the use of echocardiography, it is often difficult to correctly position the VVDL cannula in neonates due to patient size and anatomy. Cannula malposition may contribute to inadequate hemodynamic support necessitating conversion to veno-arterial (V-A) support. We report a case of successful conversion from VVDL ECMO to V-A ECMO using the 13-French Avalon cannula in a neonate. This case demonstrates that the 13 French-Avalon Elite Bi-caval Dual Lumen Cannula can be safely used as a venous cannula in neonates requiring conversion to V-A ECMO.