Infant RSV infection desensitizes β2-adrenergic receptor via CXCL11-CXCR7 signaling in airway smooth muscle.

Rationale: Airflow obstruction refractory to β2 adrenergic receptor (β2AR) agonists is an important clinical feature of infant respiratory syncytial virus (RSV) bronchiolitis, with limited treatment options. This resistance is often linked to poor drug delivery and potential viral infection of airway smooth muscle cells (ASMCs). Whether RSV inflammation causes β2AR desensitization in infant ASMCs is unknown.

Fetal Tracheal Occlusion Corelates with Normalized YAP Expression and Alveolar Epithelial Differentiation in CDH.

Congenital diaphragmatic hernia (CDH) is characterized by incomplete closure of the diaphragm. While the ensuing compression to the fetal lung causes lung hypoplasia, specific cellular phenotypes and developmental signaling defects in the alveolar epithelium in CDH are not fully understood. Employing lung samples from human CDH, a surgical lamb model and a nitrogen rat model, we investigate whether lung compression impairs alveolar epithelial differentiation and Yes-associated protein (YAP)-mediated mechanosensing.

Activation of STAT3-mediated ciliated cell survival protects against severe infection by respiratory syncytial virus.

Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia, mostly in infants. To identify molecular targets of intervention during RSV infection in infants, we investigated how age regulates RSV interaction with the bronchial epithelium barrier. Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium.

Parental Self-Efficacy and Personal Time Help Explain Impact of Parent-Staff Interactions on Parental Distress and Bonding in the Neonatal Intensive Care Unit.

Objectives: To identify factors that help explain associations between parent-staff interactions and: (1) parental depression, anxiety, and post-traumatic stress; and (2) parent-child bonding in the neonatal intensive care unit.

Study Design: Our cross-sectional mixed methods survey investigated the ways in which parental-staff interactions relate to parental distress and parent-child bonding. Parents with babies in the neonatal intensive care unit (n = 165) completed validated measures and open-ended questions about their experiences with staff.

Prevention of NICU Admission Hypothermia in Moderate- and Late-Preterm Infants.

Background: Neonatal hypothermia is a common and preventable cause of neonatal morbidity and mortality. Although hypothermia prevention has been extensively studied in infants <32 weeks' gestation, the authors of few studies have targeted moderate- and late-preterm infants (MLPIs) in the delivery room.

Methods: This quality improvement initiative was conducted from June 2019 to June 2023 at the Massachusetts General Hospital NICU and Labor and Delivery Unit.

Bilirubin Measurement and Phototherapy Use After the AAP 2022 Newborn Hyperbilirubinemia Guideline.

Background And Objectives: Guidelines for the management of neonatal hyperbilirubinemia have helped to reduce rates of significant hyperbilirubinemia. However, recent evidence suggesting overtreatment and potential harms of phototherapy have informed the American Academy of Pediatrics clinical practice guideline revision and the accompanying increase in phototherapy thresholds. These changes are predicted to safely reduce overuse; however, to date, the exact effect of these guidelines has not been established.

Age-related STAT3 signaling regulates severity of respiratory syncytial viral infection in human bronchial epithelial cells.

Respiratory syncytial virus (RSV) can cause severe disease especially in infants; however, mechanisms of age-associated disease severity remain elusive. Here, employing human bronchial epithelium models generated from tracheal aspirate-derived basal stem cells of neonates and adults, we investigated whether age regulates RSV-epithelium interaction to determine disease severity. We show that following RSV infection, only neonatal epithelium model exhibited cytopathy and mucus hyperplasia, and neonatal epithelium had more robust viral spread and inflammatory responses than adult epithelium.

Airway Basal Stem Cells in COVID-19 Exhibit a Proinflammatory Signature and Impaired Mucocililary Differentiation.

Airway basal stem cells (BSCs) play a critical role in epithelial regeneration. Whether coronavirus disease (COVID-19) affects BSC function is unknown. Here, we derived BSC lines from patients with COVID-19 using tracheal aspirates (TAs) to circumvent the biosafety concerns of live-cell derivation.

Limited Utility of Toxicology Testing at Delivery for Perinatal Cannabis Use.

Objectives: To describe the characteristics of individuals undergoing toxicology testing at delivery for a sole indication of cannabis use and to evaluate the rate of unexpected positive toxicology testing results among this cohort.

Methods: This retrospective cohort study included dyads with a maternal history of cannabis use who underwent peripartum toxicology testing between 2016 and 2020 at 5 birthing hospitals in Massachusetts. We collected information on maternal demographic characteristics and toxicology test results and reviewed records of dyads with unexpected positive results to identify additional social risk factors and clinical outcomes.

Human Airway Basal Cells Undergo Reversible Squamous Differentiation and Reshape Innate Immunity.

Histological and lineage immunofluorescence examination revealed that healthy conducting airways of humans and animals harbor sporadic poorly differentiated epithelial patches mostly in the dorsal noncartilage regions that remarkably manifest squamous differentiation. analysis demonstrated that this squamous phenotype is not due to intrinsic functional change in underlying airway basal cells. Rather, it is a reversible physiological response to persistent Wnt signaling stimulation during differentiation.

A Tracheal Aspirate-derived Airway Basal Cell Model Reveals a Proinflammatory Epithelial Defect in Congenital Diaphragmatic Hernia.

Congenital diaphragmatic hernia (CDH) is characterized by incomplete closure of the diaphragm and lung hypoplasia. The pathophysiology of lung defects in CDH is poorly understood. To establish a translational model of human airway epithelium in CDH for pathogenic investigation and therapeutic testing.

Standardizing the Evaluation and Management of Necrotizing Enterocolitis in a Level IV NICU.

Objectives: Necrotizing enterocolitis (NEC) is a severe intestinal inflammatory disease and a leading cause of morbidity and mortality in NICUs. Management of NEC is variable because of the lack of evidence-based recommendations. It is widely accepted that standardization of patient care leads to improved outcomes.

Caring for our caretakers: building resiliency in NICU parents and staff.

Unlabelled: The neonatal intensive care unit (NICU) is a high-acuity, stressful unit for both parents and staff. Up to 50% of mothers and partners experience emotional distress (i.e.

Primary culture of tracheal aspirate-derived human airway basal stem cells.

Patient-specific airway basal stem cells (BSCs) can be derived from tracheal aspirate (TA) samples from intubated patients, thus providing an invaluable lung stem cell derivation method that bypasses the need for lung tissue. The primary culture of BSCs provides the ideal model to study the function and differentiation of the conducting lung epithelium. This protocol outlines the specific steps for isolation, culture maintenance, passaging, freezing, thawing, differentiation, and immunofluorescence characterization of human TA-derived airway BSCs.

Single-cell immunophenotyping of the fetal immune response to maternal SARS-CoV-2 infection in late gestation.

Background: During the COVID-19 pandemic, thousands of pregnant women have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The implications of maternal SARS-CoV-2 infection on fetal and childhood well-being need to be characterized. We aimed to characterize the fetal immune response to maternal SARS-CoV-2 infection.

Improving Timeliness of Hepatitis B Vaccine Birth Dose Administration.

Background And Objectives: When given within 24 hours of birth, the hepatitis B vaccine is up to 90% effective in preventing perinatal infection. The American Academy of Pediatrics now recommends administration within 24 hours for infants with a birth weight >2 kg, but a national benchmark for compliance with this time frame has not been established. We aimed to increase the monthly average of eligible newborns receiving the vaccine on time from 40% to 80% over a 9-month period.

Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic.

Importance: Biological data are lacking with respect to risk of vertical transmission and mechanisms of fetoplacental protection in maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Objective: To quantify SARS-CoV-2 viral load in maternal and neonatal biofluids, transplacental passage of anti-SARS-CoV-2 antibody, and incidence of fetoplacental infection.

Design, Setting, And Participants: This cohort study was conducted among pregnant women presenting for care at 3 tertiary care centers in Boston, Massachusetts.

Establishment of a pediatric COVID-19 biorepository: unique considerations and opportunities for studying the impact of the COVID-19 pandemic on children.

Background: COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. This biorepository enables pediatric centers world-wide to collect samples uniformly to drive forward our understanding of COVID-19 by addressing specific pediatric and neonatal COVID-19-related questions.

Rapid establishment of a COVID-19 perinatal biorepository: early lessons from the first 100 women enrolled.

Background: Collection of biospecimens is a critical first step to understanding the impact of COVID-19 on pregnant women and newborns - vulnerable populations that are challenging to enroll and at risk of exclusion from research. We describe the establishment of a COVID-19 perinatal biorepository, the unique challenges imposed by the COVID-19 pandemic, and strategies used to overcome them.

Methods: A transdisciplinary approach was developed to maximize the enrollment of pregnant women and their newborns into a COVID-19 prospective cohort and tissue biorepository, established on March 19, 2020 at Massachusetts General Hospital (MGH).

Pediatric Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Clinical Presentation, Infectivity, and Immune Responses.

Objectives: As schools plan for re-opening, understanding the potential role children play in the coronavirus infectious disease 2019 (COVID-19) pandemic and the factors that drive severe illness in children is critical.

Study Design: Children ages 0-22 years with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presenting to urgent care clinics or being hospitalized for confirmed/suspected SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) at Massachusetts General Hospital were offered enrollment in the Massachusetts General Hospital Pediatric COVID-19 Biorepository. Enrolled children provided nasopharyngeal, oropharyngeal, and/or blood specimens.

Establishment of a Pediatric COVID-19 Biorepository: Unique Considerations and Opportunities for Studying the Impact of the COVID-19 Pandemic on Children.

Background: COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. This biorepository enables pediatric centers world-wide to collect samples uniformly to drive forward our understanding of COVID-19 by addressing specific pediatric and neonatal COVID-19-related questions.

Rho/SMAD/mTOR triple inhibition enables long-term expansion of human neonatal tracheal aspirate-derived airway basal cell-like cells.

Background: Bronchopulmonary dysplasia remains one of the most common complications of prematurity, despite significant improvements in perinatal care. Functional modeling of human lung development and disease, like BPD, is limited by our ability to access the lung and to maintain relevant progenitor cell populations in culture.

Methods: We supplemented Rho/SMAD signaling inhibition with mTOR inhibition to generate epithelial basal cell-like cell lines from tracheal aspirates of neonates.