Development and use of an infant resuscitation performance tool (Infa-RePT) to improve team performance.

BACKGROUND: Measurement of neonatal team resuscitation performance is critical to identify opportunities for improvement and to target education. An effective tool to measure team performance during infant resuscitations is lacking. METHODS: We developed an in-hospital infant resuscitation performance tool (Infa-RePT) using the modified Delphi method. We employed a QI framework and targeted interventions, including the use of role responsibility checklists, mock codes, and an educational video. We tracked Infa-RePT scores, mock code team attendance, and confidence surveys. Our specific aim was to improve Infa-RePT score from a baseline of 7.4 to <5 (lower is better) over a 26-month period. RESULTS: Twenty-five elements reached >80% consensus as essential components to include on the Infa-RePT. Independent observation showed 86% concordance on checklist items. Simulation (n = 26) and unit-based code (n = 10) Infa-RePT scores showed significant improvement after project start from 7.4 to 4.2 (p < 0.01) with special cause variation noted on control chart analysis. No significant difference was observed between simulations and in-unit codes. Staff confidence self-reports improved over the study period. CONCLUSIONS: Use of a novel scoring tool can help monitor team progress over time and identify areas for improvement. Focused interventions can improve resuscitation team performance. IMPACT: We developed and used a novel, comprehensive measurement tool for team infant resuscitation performance in both simulation and in-unit settings. Using QI methodology, team performance improved after the enhancement of a mock code simulation program. Review of team performance scores can highlight key areas to target interventions and monitor progress over time.

A mixed methods study of perceptions of bias among neonatal intensive care unit staff.

BACKGROUND: Inequity in neonatology may be potentiated within neonatal intensive care units (NICUs) by the effects of bias. Addressing bias can lead to improved, more equitable care. Understanding perceptions of bias can inform targeted interventions to reduce the impact of bias. We conducted a mixed methods study to characterize the perceptions of bias among NICU staff. METHODS: Surveys were distributed to all staff (N = 245) in a single academic Level IV NICU. Respondents rated the impact of bias on their own and others' behaviors on 5-point Likert scales and answered one open-ended question. Kruskal-Wallis test (KWT) and Levene's test were used for quantitative analysis and thematic analysis was used for qualitative analysis. RESULTS: We received 178 responses. More respondents agreed that bias had a greater impact on others' vs. their own behaviors (KWT p < 0.05). Respondents agreed that behaviors were influenced more by implicit than explicit biases (KWT p < 0.05). Qualitative analysis resulted in nine unique themes. CONCLUSIONS: Staff perceive a high impact of bias across different domains with increased perceived impact of implicit vs. explicit bias. Staff perceive a greater impact of others' biases vs. their own. Mixed methods studies can help identify unique, unit-responsive approaches to reduce bias. IMPACT: Healthcare staff have awareness of bias and its impact on their behaviors with patients, families, and staff. Healthcare staff believe that implicit bias impacts their behaviors more than explicit bias, and that they have less bias than others. Healthcare staff have ideas for strategies and approaches to mitigate the impact of bias. Mixed method studies are effective ways of understanding environment-specific perceptions of bias, and contextual assets and barriers when creating interventions to reduce bias and improve equity. Generating interventions to reduce the impact of bias in healthcare requires a context-specific understanding of perceptions of bias among staff.

Ventilatory Strategies in Infants with Established Severe Bronchopulmonary Dysplasia: A Multicenter Point Prevalence Study.

We performed a point prevalence study on infants with severe bronchopulmonary dysplasia (BPD), collecting data on type and settings of ventilatory support; 187 infants, 51% of whom were on invasive positive-pressure ventilation (IPPV), from 15 centers were included. We found a significant center-specific variation in ventilator modes.

Ethical implications of early genetic diagnosis in an infant with Lesch-Nyhan syndrome.

Pathogenic variants in HPRT1 lead to deficiency in hypoxanthine-guanine phosphoribosyltransferase and are responsible for a spectrum of disorders. The severe phenotype is termed Lesch-Nyhan syndrome (LNS) and is inherited in an X-linked recessive manner. Most individuals with LNS have profound intellectual and physical disabilities throughout life including self-mutilating behaviors. Here, we present the case of a male infant who was diagnosed with LNS at 3 weeks of age via rapid exome sequencing (ES), which revealed a hemizygous maternally inherited deletion of at least 1.3 Mb of Xq26.3, including exons 2 to 9 of HPRT1. We discuss the critical time points leading to this diagnosis while highlighting his parents' values that guided the decision-making. Genetic testing provided an early diagnosis for this infant that led to important considerations regarding goals of care in addition to raising new ethical concerns. This highlights the important role that early and rapid diagnostic genetic testing can play in helping families make difficult decisions. Additionally, this case highlights the complexity of discussing rare genetic diagnoses with families and facilitating critical discussions to empower the family toward making an informed decision.

The 21st Century Cures Act: Perspectives of Clinicians in a Level-IV Neonatal Intensive Care Unit.

OBJECTIVE: Our objective is to describe the implications, anticipated and perceived, by providers in a level-IV neonatal intensive care unit (NICU) with immediate patient access to inpatient notes and test results in the wake of the 21st Century Cures Act (CCA). STUDY DESIGN: Using a mixed-method approach in February 2021, a preimplementation survey of neonatologists, neonatal fellows, nurse practitioners, and neonatal nurses reported their perspectives on the new 21st CCA and how they anticipated that it would change their practices, and the experience of families in the NICU. In the follow-up to implementation, a postsurvey was completed by staff reporting their experiences in July 2021. Thematic analysis was performed. RESULTS: In the preimplementation survey, staff reported the greatest perceived benefits of the changes to be an increase in families' ability to be part of the care team and prepare questions, and faster discussion of results by the care team. Also, staff's highest concerns were that family members may incorrectly interpret results delivered electronically without the context provided by the care team and be overwhelmed by the amount of information available. In the postimplementation survey, staff reported that the Act had less impact on their practice than they had anticipated preimplementation. CONCLUSION: To maximize benefits and limit burdens to families and staff, care teams should consider a thoughtful approach to information sharing with family members in compliance with the 21st CCA. KEY POINTS: · The impact of the 21 CCA on the NICU has not been studied.. · NICU staff have significant concerns related to the release of results to families.. · This study highlights the need to set expectations and provide family-centered care..

Prematurity negatively affects regenerative properties of human amniotic epithelial cells in the context of lung repair.

There is a growing appreciation of the role of lung stem/progenitor cells in the development and perpetuation of chronic lung disease including idiopathic pulmonary fibrosis. Human amniotic epithelial cells (hAECs) were previously shown to improve lung architecture in bleomycin-induced lung injury, with the further suggestion that hAECs obtained from term pregnancies possessed superior anti-fibrotic properties compared with their preterm counterparts. In the present study, we aimed to elucidate the differential effects of hAECs from term and preterm pregnancies on lung stem/progenitor cells involved in the repair. Here we showed that term hAECs were better able to activate bronchioalveolar stem cells (BASCs) and type 2 alveolar epithelial cells (AT2s) compared with preterm hAECs following bleomycin challenge. Further, we observed that term hAECs restored TGIF1 and TGFß2 expression levels, while increasing c-MYC expression despite an absence of significant changes to Wnt/ß-catenin signaling. In vitro, term hAECs increased the average size and numbers of BASC and AT2 colonies. The gene expression levels of Wnt ligands were higher in term hAECs, and the expression levels of BMP4, CCND1 and CDC42 were only increased in the BASC and AT2 organoids co-cultured with hAECs from term pregnancies but not preterm pregnancies. In conclusion, term hAECs were more efficient at activating the BASC niche compared with preterm hAECs. The impact of gestational age and/or complications leading to preterm delivery should be considered when applying hAECs and other gestational tissue-derived stem and stem-like cells therapeutically.

A Device for the Quantification of Oxygen Consumption and Caloric Expenditure in the Neonatal Range.

BACKGROUND: The accurate measurement of oxygen consumption (VO2) and energy expenditure (EE) may be helpful to optimize the treatment of critically ill patients. However, current techniques are limited in their ability to accurately quantify these end points in infants due to a low VO2, low tidal volume, and rapid respiratory rate. This study describes and validates a new device intended to perform in this size range. METHODS: We created a customized device that quantifies inspiratory volume using a pneumotachometer and concentrations of oxygen and carbon dioxide gas in the inspiratory and expiratory limbs. We created a customized algorithm to achieve precise time alignment of these measures, incorporating bias flow and compliance factors. The device was validated in 3 ways. First, we infused a certified gas mixture (50% oxygen/50% carbon dioxide) into an artificial lung circuit, comparing measured with simulated VO2 and carbon dioxide production (VCO2) within a matrix of varying tidal volume (4-20 mL), respiratory rate (20-80 bpm), and fraction of inspired oxygen (0.21-0.8). Second, VO2, VCO2, and EE were measured in Sprague Dawley rats under mechanical ventilation and were compared to simultaneous Douglas bag collections. Third, the device was studied on n = 14 intubated, spontaneously breathing neonates and infants, comparing measured values to Douglas measurements. In all cases, we assessed for difference between the device and reference standard by linear regression and Bland-Altman analysis. RESULTS: In vitro, the mean ± standard deviation difference between the measured and reference standard VO2 was +0.04 ± 1.10 (95% limits of agreement, -2.11 to +2.20) mL/min and VCO2 was +0.26 ± 0.31 (-0.36 to +0.89) mL/min; differences were similar at each respiratory rate and tidal volume measured, but higher at fraction of inspired oxygen of 0.8 than at 0.7 or lower. In rodents, the mean difference was -0.20 ± 0.55 (-1.28 to +0.89) mL/min for VO2, +0.16 ± 0.25 (-0.32 to +0.65) mL/min for VCO2, and -0.84 ± 3.29 (-7.30 to +5.61) kcal/d for EE. In infants, the mean VO2 was 9.0 ± 2.5 mL/kg/min by Douglas method and was accurately measured by the device (bias, +0.22 ± 0.87 [-1.49 to +1.93] mL/kg/min). The average VCO2 was 8.1 ± 2.3 mL/kg/min, and the device exhibited a bias of +0.33 ± 0.82 (-1.27 to +1.94) mL/kg/min. Mean bias was +2.56% ± 11.60% of the reading for VO2 and +4.25% ± 11.20% of the reading for VCO2; among 56 replicates, 6 measurements fell outside of the 20% error range, and no patient had >1 of 4 replicates with a >20% error in either VO2 or VCO2. CONCLUSIONS: This device can measure VO2, VCO2, and EE with sufficient accuracy for clinical decision-making within the neonatal and pediatric size range, including in the setting of tachypnea or hyperoxia.

Neurotrophin receptor TrkB promotes lung adenocarcinoma metastasis.

Lung cancer is notorious for its ability to metastasize, but the pathways regulating lung cancer metastasis are largely unknown. An in vitro system designed to discover factors critical for lung cancer cell migration identified brain-derived neurotrophic factor, which stimulates cell migration through activation of tropomyosin-related kinase B (TrkB; also called NTRK2). Knockdown of TrkB in human lung cancer cell lines significantly decreased their migratory and metastatic ability in vitro and in vivo. In an autochthonous lung adenocarcinoma model driven by activated oncogenic Kras and p53 loss, TrkB deficiency significantly reduced metastasis. Hypoxia-inducible factor-1 directly regulated TrkB expression, and, in turn, TrkB activated Akt signaling in metastatic lung cancer cells. Finally, TrkB expression was correlated with metastasis in patient samples, and TrkB was detected more often in tumors that did not have Kras or epidermal growth factor receptor mutations. These studies demonstrate that TrkB is an important therapeutic target in metastatic lung adenocarcinoma.

Sustaining careers of physician-scientists in neonatology and pediatric critical care medicine: formulating supportive departmental policies.

Understanding mechanisms of childhood disease and development of rational therapeutics are fundamental to progress in pediatric intensive care specialties. However, Division Chiefs and Department Chairs face unique challenges when building effective laboratory-based research programs in Neonatal and Pediatric Intensive Care, owing to high clinical demands necessary to maintain competence as well as financial pressures arising from fund flow models and the current extramural funding climate. Given these factors, the role of institutional support that could facilitate successful transition of promising junior faculty to independent research careers is ever more important. Would standardized guidelines of such support provide greater consistency among institutions? We addressed preliminary questions during a national focus group, a workshop and a survey of junior and senior academicians to solicit recommendations for optimal levels of protected time and resources when starting an independent laboratory. The consensus was that junior faculty should be assigned no more than 8 wk clinical service and should obtain start-up funds of $500K-1M exclusive of a 5-y committed salary support. Senior respondents placed a higher premium on protected time than junior faculty.

Neonatal respiratory care practice among level III and IV NICUs in New England.

OBJECTIVES: To assess respiratory care guidelines and explore variations in management of very low birth weight (VLBW) infants within a collaborative care framework. Additionally, to gather clinical leaders' perspectives on guidelines and preferences for ventilation modalities. STUDY DESIGN: Leaders from each NICU participated in a practice survey regarding the prevalence of unit clinical guidelines, and management, at many stages of care. RESULTS: Units have an average of 4.3 (±2.1) guidelines, of 9 topics queried. Guideline prevalence was not associated with practice or outcomes. An FiO2 requirement of 0.3-0.4 and a CPAP of 6-7 cmH2O, are the most common thresholds for surfactant administration, which is most often done after intubation, and followed by weaning from ventilatory support. Volume targeted ventilation is commonly used. Extubation criteria vary widely. CONCLUSIONS: Results identify trends and areas of variation and suggest that the presence of guidelines alone is not predictive of outcome.

Transpyloric feeding is associated with adverse in-hospital outcomes in infants with severe bronchopulmonary dysplasia.

OBJECTIVE: To estimate the association of transpyloric feeding (TPF) with the composite outcome of tracheostomy or death for patients with severe bronchopulmonary dysplasia (sBPD). STUDY DESIGN: Retrospective multi-center cohort study of preterm infants <32 weeks with sBPD receiving enteral feedings. We compared infants who received TPF at 36, 44, or 50 weeks post-menstrual age to those who did not receive TPF at any of those timepoints. Odds ratios were adjusted for gestational age, small for gestational age, male sex, and invasive ventilation and FiO2 at 36 weeks. RESULTS: Among 1039 patients, 129 (12%) received TPF. TPF was associated with an increased odds of tracheostomy or death (aOR 3.5, 95% CI 2.0-6.1) and prolonged length of stay or death (aOR 3.1, 95% CI 1.9-5.2). CONCLUSIONS: Use of TPF in sBPD after 36 weeks was infrequent and associated with worse in-hospital outcomes, even after adjusting for respiratory severity at 36 weeks.

Neonatal platelet transfusions: New evidence and the challenges of translating evidence-based recommendations into clinical practice.

Platelet transfusions are a common intervention for thrombocytopenia. Although the main reason for transfusing platelets is to improve hemostasis, platelets have many additional physiological roles, including interactions with immune pathways. Much of the evidence base for safe and effective transfusions has been informed by randomized trials in adult patients with hematological malignancies. Only three randomized trials have been conducted in sick neonates. These trials have indicated evidence of harm, including a significantly higher rate of death or major bleeding within 28 days after randomization for the largest trial, which enrolled 660 infants. The overall research indicates limited effectiveness of platelet transfusions to reduce bleeding risk. It is important that the results of trials are implemented into practice, but uptake of research findings into neonatal medicine remains inconsistent, as for many areas of health care. There is a need to establish which potential implementation strategies (cost-) efficiently enact change, such as audit and feedback, automated reminder systems for ordering transfusions, and use of opinion leaders. Research is exploring potential mechanisms underlying the lack of effectiveness of platelet transfusions and the increased bleeding and mortality observed in neonatal randomized trials. One potential mechanism concerns the roles of platelets to promote excessive angiogenic signals during a vulnerable period of brain development. A further hypothesis explores the effects of transfusing "adult" platelets into "neonatal" thrombocytopenic blood on primary hemostasis and immune responses.

Mortality in the neonatal intensive care unit: improving the accuracy of death reporting.

OBJECTIVE: Death certificates commonly contain errors, which hinders understanding of infant mortality. We, therefore, undertook a quality improvement (QI) initiative to improve death reporting in our neonatal intensive care unit (NICU). STUDY DESIGN: After our baseline assessment (January 1, 2015 to June 30, 2017), we implemented our QI initiatives using Plan, Do, Study, Act (PDSA) tests of change. We prospectively reviewed death certificates (July 1, 2017 to December 31, 2019) to evaluate the impact of our interventions. RESULTS: The overall proportion of incorrect death certificates significantly decreased from 71 to 22% with special cause variation noted after the second PDSA cycle. The most common errors involved inaccurate or incomplete reporting of prematurity and errors in the sequence of events. CONCLUSION: Through a series of PDSA cycles focused on formal provider education and ongoing review, we significantly reduced inaccurate death reporting. These interventions are generalizable across NICUs and important to improve public health reporting accuracy.

Diagnosis and management of pulmonary hypertension in infants with bronchopulmonary dysplasia.

Chronic pulmonary hypertension of infancy (cPHi) is a heterogeneous disease process that contributes to morbidity and mortality in preterm infants. cPHi is most commonly associated with chronic lung disease of prematurity and represents a unique phenotype of bronchopulmonary dysplasia. It is characterized by persistently elevated or newly rising pulmonary vascular resistance and pulmonary artery pressure beyond the first weeks of age. The high-pressure afterload on the right ventricle may or may not be tolerated, depending upon additional cardiovascular shunting and co-morbidities. A comprehensive clinical evaluation combined with advanced hemodynamic assessment by echocardiography and other cardiac imaging modalities help decipher the etiopathologies of disease, identify cardiopulmonary compromise earlier and guide individualized therapeutic intervention tailored by the phenotype. This review summarizes the underlying etiologies, risk factors for development, hemodynamic assessment, management, and follow-up of cPHi in preterm infants. We offer an algorithm for early detection of cPHi and outline research priorities.

Essentials of Neonatal-Perinatal Medicine fellowship: an overview.

Neonatal-Perinatal Medicine (NPM) fellowship programs have undergone constant evolution since their first appearance in the 1960s. This article is the first in a seven-part series (Table 1) that critically evaluates the essentials of neonatology fellowship clinical and research education, performance assessment, and administrative support necessary to support NPM fellowship programs. This overview article will provide background on the history of NPM fellowship programs and provide a framework for the article series. Table 1 Essentials of NPM fellowship article series. Essentials of NPM fellowship Part 1: Overview of NPM fellowship Description of the evolution of NPM Fellowship Part 2: Clinical education and experience Strengths, weaknesses, opportunities, and threats of clinical education in NPM fellowship Part 3: Scholarship opportunities and threats Scholarship requirements during NPM fellowship Part 4: Innovations in medical education Critical analysis of current educational practices and andragogical innovations in NPM fellowship Part 5: Evaluation of competence and proficiency using milestones Assessment of NPM fellows during training using competency-based medical education principles Part 6: Program administration Administrative infrastructure and stakeholders necessary to run a NPM fellowship program Part 7: Careers in NPM Career preparation and opportunities for NPM fellowship graduates.

Implementation of a neonatal platelet transfusion guideline to reduce non-indicated transfusions using a quality improvement framework.

OBJECTIVE: Variation exists in neonatal platelet transfusion practices. Recent studies found potential harm in liberal platelet transfusion practices, supporting the use of lower transfusion thresholds. Our aim was to reduce non-indicated platelet transfusions through implementation of a restrictive platelet transfusion guideline. STUDY DESIGN: Platelet transfusions from January 2017 to December 2019 were classified as indicated or non-indicated using the new guideline. Interventions included guideline implementation and staff education. Outcomes were evaluated using statistical process control charts. Major bleeding was the balancing measure. RESULT: During study, 438 platelet transfusions were administered to 105 neonates. The mean number of non-indicated platelet transfusions/month decreased from 7.3 to 1.6. The rate of non-indicated platelet transfusions per 100 patient admissions decreased from 12.5 to 2.9. Rates of major bleeding remained stable. CONCLUSIONS: Implementation of a restrictive neonatal platelet transfusion guideline significantly reduced potentially harmful platelet transfusions in our NICU without a change in major bleeding.

COVID-19: neonatal-perinatal perspectives.

The coronavirus disease 2019 (COVID-19) pandemic, resulting from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused severe and widespread illness in adults, including pregnant women, while rarely infecting neonates. An incomplete understanding of disease pathogenesis and viral spread has resulted in evolving guidelines to reduce transmission from infected mothers to neonates. Fortunately, the risk of neonatal infection via perinatal/postnatal transmission is low when recommended precautions are followed. However, the psychosocial implications of these practices and racial/ethnic disparities highlighted by this pandemic must also be addressed when caring for mothers and their newborns. This review provides a comprehensive overview of neonatal-perinatal perspectives of COVID-19, ranging from the basic science of infection and recommendations for care of pregnant women and neonates to important psychosocial, ethical, and racial/ethnic topics emerging as a result of both the pandemic and the response of the healthcare community to the care of infected individuals.

Association of nucleated red blood cell count with mortality among neonatal intensive care unit patients.

BACKGROUND: Nucleated red blood cells (nRBCs) are associated with adverse outcomes for pediatric and adult intensive care patients. METHODS: The association between nRBC count and mortality was examined in an observational cohort of patients admitted to the neonatal intensive care unit from December 2015-December 2018. RESULTS: Among the 1059 patients with at least one nRBC count obtained, 45 infants (4.2%) experienced in-hospital mortality prior to NICU discharge, the primary outcome measured in this study. Infants with any nRBC count >0 had a significantly higher risk of mortality (5.3% [45/849] vs. 0% [0/351], p < 0.001 by Fisher exact), and time to mortality decreased with higher nRBC counts (Spearman correlation -0.59, p < 0.001). The association between nRBC count and mortality remained significant even when restricting only to infants who were older than 7 days at time of nRBC count. CONCLUSION: Among neonatal intensive care unit patients, including those >7 days old, nRBCs are associated with significantly elevated mortality risk. A prospective study to better characterize clinical co-variants is necessary to better establish the use of nRBCs as a predictor of mortality.

Screening With Reticulocyte Hemoglobin Increased Iron Sufficiency Among NICU Patients.

INTRODUCTION: To increase the rate of iron sufficiency among neonatal intensive care unit (NICU) patients from 16% to >35% within 12 months of implementing standardized assessment of reticulocyte hemoglobin (retHE). METHODS: We implemented a quality improvement (QI) study to improve iron sufficiency in our out-born level III/IV NICU. We screened 2,062 admissions, of which 622 were eligible based on feeding status at discharge. QI interventions included educational efforts and guideline implementation. Our primary outcome measure was the percentage of patients with their discharge retHE measure within the normal range. We also tracked the process measure of the number of retHE tests performed and a balancing measure of the incidence of elevated retHE among patients receiving iron supplementation. Statistical process control (SPC) charts assessed for special cause variation. RESULTS: The percentage of patients with a retHe within the normal range was significantly increased from a mean of 20% to 39% on SPC chart analysis. We measured significantly more retHE values after guideline implementation (11/mo to 24/mo) and found no cases of elevated retHE among patients receiving iron supplementation. CONCLUSIONS: After the implementation of a standardized guideline, a higher rate of iron sufficiency was found in NICU patients at discharge. This work is generalizable to neonatal populations with the potential for a significant impact on clinical practice.

Mesenchymal Stem Cells Increase Alveolar Differentiation in Lung Progenitor Organoid Cultures.

Lung epithelial cell damage and dysfunctional repair play a role in the development of lung disease. Effective repair likely requires the normal functioning of alveolar stem/progenitor cells. For example, we have shown in a mouse model of bronchopulmonary dysplasia (BPD) that mesenchymal stem cells (MSC) protect against hyperoxic lung injury at least in part by increasing the number of Epcam+ Sca-1+ distal lung epithelial cells. These cells are capable of differentiating into both small airway (CCSP+) and alveolar (SPC+) epithelial cells in three-dimensional (3D) organoid cultures. To further understand the interactions between MSC and distal lung epithelial cells, we added MSC to lung progenitor 3D cultures. MSC stimulated Epcam+ Sca-1+ derived organoid formation, increased alveolar differentiation and decreased self-renewal. MSC-conditioned media was sufficient to promote alveolar organoid formation, demonstrating that soluble factors secreted by MSC are likely responsible for the response. This work provides strong evidence of a direct effect of MSC-secreted factors on lung progenitor cell differentiation.