Special Issue "Neonatal Respiratory Distress"

A special issue of Children (ISSN 2227-9067).

Deadline for manuscript submissions: closed (15 February 2021).

Special Issue Editors

Prof. Rita Marie Ryan
E-Mail Website
Guest Editor
School of Medicine, Case Western Reserve University, UH Rainbow Babies and Children’s Hospital, Cleveland, OH 44106, USA
Interests: neonatal lung biology; hyperoxia; surfactant; natriuretic peptide system
Special Issues and Collections in MDPI journals
Dr. Thomas M. Raffay
E-Mail Website
Guest Editor
School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
Interests: the developing lung; nitrosylated compounds; bronchial airway hyperreactivity; oxygenation patterns
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Neonatal respiratory distress is a broad, but very common problem. We hope to highlight novel concepts regarding the pathophysiology of neonatal respiratory distress, including those involving classic respiratory distress syndrome (RDS)/surfactant deficiency, persistent pulmonary hypertension of the newborn (PPHN), pulmonary insufficiency of prematurity (factors related to the need for respiratory support due to small size, immaturity, control of breathing, etc.), and evolving early bronchopulmonary dysplasia (BPD), as well as less common etiologies of neonatal respiratory distress such as acute lung injury/acute (adult) RDS (ARDS), congenital diaphragmatic hernia (CDH), tracheomalacia, and other anatomic problems. We are seeking both reviews, highlighting gaps in knowledge, as well as original research, including pilot studies and translational laboratory studies pertinent to the topic.  We are especially interested in studies supporting or introducing novel therapies and their mechanisms of action, such as new modes of surfactant delivery, antenatal and perinatal steroids, anti-oxidants, and other early-stage pharmacotherapies. During the ever-changing time of the novel SARS-CoV-2 (COVID-19) pandemic, we would also welcome works pertaining to practice modifications and challenges in the delivery room management of RDS, non-invasive positive pressure, and intubation.

The goal of this Special Issue in Children is to highlight the scientific understanding of the factors that contribute to neonatal respiratory distress, as well as advances in therapeutic approaches across a variety of settings.  Senior investigators are welcome to invite mentees and colleagues to co-author submissions under their supervision.  It is our intention that this Special Issue will appeal to both newborn medical providers and neonatal researchers from a variety of backgrounds, including nurses, advanced providers, therapists, pharmacists, physicians, and scientists.

Prof. Dr. Rita Marie Ryan
Dr. Thomas M. Raffay
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Children is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neonatal lung disease
  • prematurity
  • oxygenation
  • positive pressure
  • intubation
  • newborn resuscitation
  • congenital anomalies
  • hypoxic respiratory failure
  • surfactant

Published Papers (12 papers)

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Research

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Article
A Quality Improvement Initiative to Reduce Bronchopulmonary Dysplasia in a Level 4 NICU—Golden Hour Management of Respiratory Distress Syndrome in Preterm Newborns
Children 2021, 8(4), 301; https://0-doi-org.brum.beds.ac.uk/10.3390/children8040301 - 15 Apr 2021
Viewed by 837
Abstract
Background: Prevention of chronic lung disease (CLD) requires a multidisciplinary approach spanning from the delivery room to Neonatal Intensive Care Unit (NICU) discharge. In 2018, a quality improvement (QI) initiative commenced in a level 4 NICU with the goal of decreasing chronic lung [...] Read more.
Background: Prevention of chronic lung disease (CLD) requires a multidisciplinary approach spanning from the delivery room to Neonatal Intensive Care Unit (NICU) discharge. In 2018, a quality improvement (QI) initiative commenced in a level 4 NICU with the goal of decreasing chronic lung disease rates below the Vermont Oxford Network (VON) average of 24%. Methods: Improvement strategies focused on addressing the primary drivers of ventilation strategies, surfactant administration, non-invasive ventilation, medication use, and nutrition/fluid management. The primary outcome was VON CLD, defined as need for mechanical ventilation and/or supplemental oxygen use at 36 weeks postmenstrual age. Statistical process control charts were used to display and analyze data over time. Results: The overall CLD rate decreased from 33.5 to 16.5% following several interventions, a 51% reduction that has been sustained for >18 months. Changes most attributable to this include implementation of the “golden hour” gestational age (GA) based delivery room protocol that encourages early surfactant administration and timely extubation. Fewer infants were intubated across all GA groups with the largest improvement among infants 26–27 weeks GA. Conclusions: Our efforts significantly decreased CLD through GA-based respiratory guidelines and a comprehensive, rigorous QI approach that can be applicable to other teams focused on improvement. Full article
(This article belongs to the Special Issue Neonatal Respiratory Distress)
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Article
Examining Variations in Surfactant Administration (ENVISION): A Neonatology Insights Pilot Project
Children 2021, 8(4), 261; https://0-doi-org.brum.beds.ac.uk/10.3390/children8040261 - 28 Mar 2021
Viewed by 520
Abstract
Variability in neonatal clinical practice is well recognized. Respiratory management involves interdisciplinary care and often is protocol driven. The most recent published guidelines for management of respiratory distress syndrome and surfactant administration were published in 2014 and may not reflect current clinical practice [...] Read more.
Variability in neonatal clinical practice is well recognized. Respiratory management involves interdisciplinary care and often is protocol driven. The most recent published guidelines for management of respiratory distress syndrome and surfactant administration were published in 2014 and may not reflect current clinical practice in the United States. The goal of this project was to better understand variability in surfactant administration through conduct of health care provider (HCP) interviews. Questions focused on known practice variations included: use of premedication, decisions to treat, technique of surfactant administration and use of guidelines. Data were analyzed for trends and results were communicated with participants. A total of 54 HCPs participated from June to September 2020. In almost all settings, neonatologists or nurse practitioners intubated the infant and respiratory therapists administered surfactant. The INSURE (INtubation-SURrfactant-Extubation) technique was practiced by 83% of participants. Premedication prior to intubation was used by 76% of HCPs. An FiO2 ≥ 30% was the most common threshold for surfactant administration (48%). In conclusion, clinical practice variations exist in respiratory management and surfactant administration and do not seem to be specific to NICU level or institution type. It is unknown what effects the variability in clinical practice might have on clinical outcomes. Full article
(This article belongs to the Special Issue Neonatal Respiratory Distress)
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Article
Extubation Readiness in Preterm Infants: Evaluating the Role of Monitoring Intermittent Hypoxemia
Children 2021, 8(3), 237; https://0-doi-org.brum.beds.ac.uk/10.3390/children8030237 - 18 Mar 2021
Viewed by 432
Abstract
Preterm infants with respiratory distress may require mechanical ventilation which is associated with increased pulmonary morbidities. Prompt and successful extubation to noninvasive support is a pressing goal. In this communication, we show original data that increased recurring intermittent hypoxemia (IH, oxygen saturation <80%) [...] Read more.
Preterm infants with respiratory distress may require mechanical ventilation which is associated with increased pulmonary morbidities. Prompt and successful extubation to noninvasive support is a pressing goal. In this communication, we show original data that increased recurring intermittent hypoxemia (IH, oxygen saturation <80%) may be associated with extubation failure at 72 h in a cohort of neonates <30 weeks gestational age. Current-generation bedside high-resolution pulse oximeters provide saturation profiles that may be of use in identifying extubation readiness and failure. A larger prospective study that utilizes intermittent hypoxemia as an adjunct predictor for extubation readiness is warranted. Full article
(This article belongs to the Special Issue Neonatal Respiratory Distress)
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Article
Prenatal Maternal Lipopolysaccharide and Mild Newborn Hyperoxia Increase Intrapulmonary Airway but Not Vessel Reactivity in a Mouse Model
Children 2021, 8(3), 195; https://0-doi-org.brum.beds.ac.uk/10.3390/children8030195 - 05 Mar 2021
Viewed by 447
Abstract
Maternal infection is a risk for preterm delivery. Preterm newborns often require supplemental oxygen to treat neonatal respiratory distress. Newborn hyperoxia exposure is associated with airway and vascular hyperreactivity, while the complications of maternal infection are variable. In a mouse model of prenatal [...] Read more.
Maternal infection is a risk for preterm delivery. Preterm newborns often require supplemental oxygen to treat neonatal respiratory distress. Newborn hyperoxia exposure is associated with airway and vascular hyperreactivity, while the complications of maternal infection are variable. In a mouse model of prenatal maternal intraperitoneal lipopolysaccharide (LPS, embryonic day 18) with subsequent newborn hyperoxia (40% oxygen × 7 days) precision-cut living lung slices were used to measure intrapulmonary airway and vascular reactivity at 21 days of age. Hyperoxia increased airway reactivity to methacholine compared to room air controls. Prenatal maternal LPS did not alter airway reactivity in room air. Combined maternal LPS and hyperoxia exposures increased airway reactivity vs. controls, although maximal responses were diminished compared to hyperoxia alone. Vessel reactivity to serotonin did not significantly differ in hyperoxia or room air; however, prenatal maternal LPS appeared to attenuate vessel reactivity in room air. Following room air recovery, LPS with hyperoxia lungs displayed upregulated inflammatory and fibrosis genes compared to room air saline controls (TNFαR1, iNOS, and TGFβ). In this model, mild newborn hyperoxia increases airway but not vessel reactivity. Prenatal maternal LPS did not further increase hyperoxic airway reactivity. However, inflammatory genes remain upregulated weeks after recovery from maternal LPS and newborn hyperoxia exposures. Full article
(This article belongs to the Special Issue Neonatal Respiratory Distress)
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Review

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Review
Molecular Mechanisms of Maternal Diabetes Effects on Fetal and Neonatal Surfactant
Children 2021, 8(4), 281; https://0-doi-org.brum.beds.ac.uk/10.3390/children8040281 - 06 Apr 2021
Cited by 1 | Viewed by 673
Abstract
Respiratory distress is a significant contributor to newborn morbidity and mortality. An association between infants of diabetic mothers (IDMs) and respiratory distress syndrome (RDS) has been well recognized for decades. As obesity and diabetes prevalence have increased over the past several decades, more [...] Read more.
Respiratory distress is a significant contributor to newborn morbidity and mortality. An association between infants of diabetic mothers (IDMs) and respiratory distress syndrome (RDS) has been well recognized for decades. As obesity and diabetes prevalence have increased over the past several decades, more women are overweight and diabetic in the first trimester, and many more pregnant women are diagnosed with gestational diabetes. Glycemic control during pregnancy can be challenging due to the maternal need for higher caloric intake and higher insulin resistance. Surfactant is a complex molecule at the alveolar air–liquid interface that reduces surface tension. Impaired surfactant synthesis is the primary etiology of RDS. In vitro cell line studies, in vivo animal studies with diabetic rat offspring, and clinical studies suggest hyperglycemia and hyperinsulinemia can disrupt surfactant lipid and protein synthesis, causing delayed maturation in surfactant in IDMs. A better understanding of the molecular mechanisms responsible for surfactant dysfunction in IDMs may improve clinical strategies to prevent diabetes-related complications and improve neonatal outcomes. Full article
(This article belongs to the Special Issue Neonatal Respiratory Distress)
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Review
Antenatal Corticosteroids: Extending the Practice for Late-Preterm and Scheduled Early-Term Deliveries?
Children 2021, 8(4), 272; https://0-doi-org.brum.beds.ac.uk/10.3390/children8040272 - 01 Apr 2021
Viewed by 418
Abstract
Respiratory distress in late-preterm and early term infants generally may warrant admission to a special care nursery or an intensive care unit. In particular, respiratory distress syndrome and transient tachypnea of the newborn are the two most common respiratory morbidities. Antenatal corticosteroids (ACS) [...] Read more.
Respiratory distress in late-preterm and early term infants generally may warrant admission to a special care nursery or an intensive care unit. In particular, respiratory distress syndrome and transient tachypnea of the newborn are the two most common respiratory morbidities. Antenatal corticosteroids (ACS) facilitate surfactant production and lung fluid resorption. The use of ACS has been proven to be beneficial for preterm infants delivered at less than 34 weeks’ gestation. Literature suggests that the benefits of giving antenatal corticosteroids may extend to late-preterm and early term infants as well. This review discusses the short-term benefits of ACS administration in reducing respiratory morbidities, in addition to potential long term adverse effects. An update on the current practices of ACS use in pregnancies greater than 34 weeks’ gestation and considerations of possibly extending versus restricting this practice to certain settings will also be provided. Full article
(This article belongs to the Special Issue Neonatal Respiratory Distress)
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Review
Neonatal Respiratory Distress Secondary to Meconium Aspiration Syndrome
Children 2021, 8(3), 246; https://0-doi-org.brum.beds.ac.uk/10.3390/children8030246 - 23 Mar 2021
Viewed by 847
Abstract
Infants born through meconium-stained amniotic fluid (MSAF) are 100 times more likely than infants born through clear amniotic fluid to develop respiratory distress in the neonatal period. Meconium aspiration syndrome (MAS) is a common cause of respiratory distress in term and post-mature neonates. [...] Read more.
Infants born through meconium-stained amniotic fluid (MSAF) are 100 times more likely than infants born through clear amniotic fluid to develop respiratory distress in the neonatal period. Meconium aspiration syndrome (MAS) is a common cause of respiratory distress in term and post-mature neonates. MAS is defined as respiratory distress accompanied by a supplemental oxygen requirement in an infant born with MSAF, in the absence of any other identified etiology to explain the symptoms. Therapy for MAS is supportive, and should be tailored to each infant’s specific pathophysiology. In cases of MAS with severe persistent pulmonary hypertension of the newborn (PPHN), patients may remain hypoxic despite aggressive ventilation, and in these cases surfactant, inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) can be life-saving. Long-term prognosis for MAS is more related to severity of initial hypoxemia and possible neurological insult than to the pulmonary pathology. Full article
(This article belongs to the Special Issue Neonatal Respiratory Distress)
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Review
Meconium Aspiration Syndrome: A Narrative Review
Children 2021, 8(3), 230; https://0-doi-org.brum.beds.ac.uk/10.3390/children8030230 - 17 Mar 2021
Viewed by 1024
Abstract
Meconium aspiration syndrome is a clinical condition characterized by respiratory failure occurring in neonates born through meconium-stained amniotic fluid. Worldwide, the incidence has declined in developed countries thanks to improved obstetric practices and perinatal care while challenges persist in developing countries. Despite the [...] Read more.
Meconium aspiration syndrome is a clinical condition characterized by respiratory failure occurring in neonates born through meconium-stained amniotic fluid. Worldwide, the incidence has declined in developed countries thanks to improved obstetric practices and perinatal care while challenges persist in developing countries. Despite the improved survival rate over the last decades, long-term morbidity among survivors remains a major concern. Since the 1960s, relevant changes have occurred in the perinatal and postnatal management of such patients but the most appropriate approach is still a matter of debate. This review offers an updated overview of the epidemiology, etiopathogenesis, diagnosis, management and prognosis of infants with meconium aspiration syndrome. Full article
(This article belongs to the Special Issue Neonatal Respiratory Distress)
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Review
Genetic Testing for Neonatal Respiratory Disease
Children 2021, 8(3), 216; https://0-doi-org.brum.beds.ac.uk/10.3390/children8030216 - 11 Mar 2021
Cited by 1 | Viewed by 603
Abstract
Genetic mechanisms are now recognized as rare causes of neonatal lung disease. Genes potentially responsible for neonatal lung disease include those encoding proteins important in surfactant function and metabolism, transcription factors important in lung development, proteins involved in ciliary assembly and function, and [...] Read more.
Genetic mechanisms are now recognized as rare causes of neonatal lung disease. Genes potentially responsible for neonatal lung disease include those encoding proteins important in surfactant function and metabolism, transcription factors important in lung development, proteins involved in ciliary assembly and function, and various other structural and immune regulation genes. The phenotypes of infants with genetic causes of neonatal lung disease may have some features that are difficult to distinguish clinically from more common, reversible causes of lung disease, and from each other. Multigene panels are now available that can allow for a specific diagnosis, providing important information for treatment and prognosis. This review discusses genes in which abnormalities are known to cause neonatal lung disease and their associated phenotypes, and advantages and limitations of genetic testing. Full article
(This article belongs to the Special Issue Neonatal Respiratory Distress)
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Review
Hydrogen Sulfide—Clues from Evolution and Implication for Neonatal Respiratory Diseases
Children 2021, 8(3), 213; https://0-doi-org.brum.beds.ac.uk/10.3390/children8030213 - 11 Mar 2021
Viewed by 474
Abstract
Reactive oxygen species (ROS) have been the focus of redox research in the realm of oxidative neonatal respiratory diseases such as bronchopulmonary dysplasia (BPD). Over the years, nitric oxide (NO) and carbon monoxide (CO) have been identified as important gaseous signaling molecules involved [...] Read more.
Reactive oxygen species (ROS) have been the focus of redox research in the realm of oxidative neonatal respiratory diseases such as bronchopulmonary dysplasia (BPD). Over the years, nitric oxide (NO) and carbon monoxide (CO) have been identified as important gaseous signaling molecules involved in modulating the redox homeostasis in the developing lung. While animal data targeting aspects of these redox pathways have been promising in treating and/or preventing experimental models of neonatal lung disease, none are particularly effective in human neonatal clinical trials. In recent years, hydrogen sulfide (H2S) has emerged as a novel gasotransmitter involved in a magnitude of cellular signaling pathways and functions. The importance of H2S signaling may lie in the fact that early life-forms evolved in a nearly anoxic, sulfur-rich environment and were dependent on H2S for energy. Recent studies have demonstrated an important role of H2S and its synthesizing enzymes in lung development, which normally takes place in a relatively hypoxic intrauterine environment. In this review, we look at clues from evolution and explore the important role that the H2S signaling pathway may play in oxidative neonatal respiratory diseases and discuss future opportunities to explore this phenomenon in the context of neonatal chronic lung disease. Full article
(This article belongs to the Special Issue Neonatal Respiratory Distress)
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Review
Respiratory Distress in the Newborn with Primary Ciliary Dyskinesia
Children 2021, 8(2), 153; https://0-doi-org.brum.beds.ac.uk/10.3390/children8020153 - 18 Feb 2021
Viewed by 596
Abstract
Primary ciliary dyskinesia (PCD) is inherited in a predominantly autosomal recessive manner with over 45 currently identified causative genes. It is a clinically heterogeneous disorder that results in a chronic wet cough and drainage from the paranasal sinuses, chronic otitis media with hearing [...] Read more.
Primary ciliary dyskinesia (PCD) is inherited in a predominantly autosomal recessive manner with over 45 currently identified causative genes. It is a clinically heterogeneous disorder that results in a chronic wet cough and drainage from the paranasal sinuses, chronic otitis media with hearing impairment as well as male infertility. Approximately 50% of patients have situs inversus totalis. Prior to the development of chronic oto-sino-pulmonary symptoms, neonatal respiratory distress occurs in more than 80% of patients as a result of impaired mucociliary clearance and mucus impaction causing atelectasis and lobar collapse. Diagnosis is often delayed due to overlapping symptoms with other causes of neonatal respiratory distress. A work up for PCD should be initiated in the newborn with compatible clinical features, especially those with respiratory distress, consistent radiographic findings or persistent oxygen requirement and/or organ laterality defects Full article
(This article belongs to the Special Issue Neonatal Respiratory Distress)
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Other

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Case Report
Neonatal Respiratory Distress and Airway Emergency: Report of Two Cases
Children 2021, 8(4), 255; https://0-doi-org.brum.beds.ac.uk/10.3390/children8040255 - 25 Mar 2021
Viewed by 518
Abstract
We discuss two cases of congenital airway malformations seen in our neonatal intensive care unit (NICU). The aim is to report extremely rare events characterized by immediate respiratory distress after delivery and the impossibility to ventilate and intubate the airway. The first case [...] Read more.
We discuss two cases of congenital airway malformations seen in our neonatal intensive care unit (NICU). The aim is to report extremely rare events characterized by immediate respiratory distress after delivery and the impossibility to ventilate and intubate the airway. The first case is a male twin born at 34 weeks by emergency caesarean section. Immediately after delivery, the newborn was cyanotic and showed severe respiratory distress. Bag-valve-mask ventilation did not relieve the respiratory distress but allowed for temporary oxygenation during subsequent unsuccessful oral-tracheal intubation (OTI) attempts. Flexible laryngoscopy revealed complete subglottic obstruction. Postmortem analysis revealed a poly-malformative syndrome, unilateral multicystic renal dysplasia with a complete subglottic diaphragm, and a tracheo-esophageal fistula (TEF). The second case is a male patient that was vaginally born at 35 weeks. Antenatally, an ultrasound (US) arose suspicion for a VACTERL association (vertebral defects, anal atresia, TEF with esophageal atresia and radial or renal dysplasia, plus cardiovascular and limb defects) and a TEF, and thus, fetal magnetic resonance (MRI) was scheduled. Spontaneous labor started shortly thereafter, before imaging could be performed. Respiratory distress, cyanosis, and absence of an audible cry was observed immediately at delivery. Attempts at OTI were unsuccessful, whereas bag-valve-mask ventilation and esophageal intubation allowed for sufficient oxygenation. An emergency tracheostomy was attempted, although no trachea could be found on cervical exploration. Postmortem analysis revealed tracheal agenesis (TA), renal dysplasia, anal atresia, and a single umbilical artery. Clinicians need to be aware of congenital airway malformations and subsequent difficulties upon endotracheal intubation and must plan for multidisciplinary management of the airway at delivery, including emergency esophageal intubation and tracheostomy. Full article
(This article belongs to the Special Issue Neonatal Respiratory Distress)
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