Cell therapy for the preterm infant: promise and practicalities

2020 ◽  
Vol 105 (5) ◽  
pp. 563-568 ◽  
Author(s):  
Elizabeth K Baker ◽  
Susan E Jacobs ◽  
Rebecca Lim ◽  
Euan M Wallace ◽  
Peter G Davis
Keyword(s):  
Brain Injury ◽  
Cell Therapy ◽  
Preterm Infant ◽  
Bronchopulmonary Dysplasia ◽  
Neonatal Intensive Care ◽  
Survival Rates ◽  
Therapeutic Approaches ◽  
New Approach ◽  
Extremely Preterm ◽  
Changing Patterns

Recent decades have seen the rapid progress of neonatal intensive care, and the survival rates of the most preterm infants are improving. This improvement is associated with changing patterns of morbidity and new phenotypes of bronchopulmonary dysplasia and preterm brain injury are recognised. Inflammation and immaturity are known contributors to their pathogenesis. However, a new phenomenon, the exhaustion of progenitor cells is emerging as an important factor. Current therapeutic approaches do not adequately address these new mechanisms of injury. Cell therapy, that is the use of stem and stem-like cells, with its potential to both repair and prevent injury, offers a new approach to these challenging conditions. This review will examine the rationale for cell therapy in the extremely preterm infant, the preclinical and early clinical evidence to support its use in bronchopulmonary dysplasia and preterm brain injury. Finally, it will address the challenges in translating cell therapy from the laboratory to early clinical trials.

scholarly journals Fate of pulmonary hypertension associated with bronchopulmonary dysplasia beyond 36 weeks postmenstrual age

2020 ◽  
Vol 106 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Sanne Arjaans ◽  
Meindina G Haarman ◽  
Marcus T R Roofthooft ◽  
Marian W F Fries ◽  
Elisabeth M W Kooi ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Bronchopulmonary Dysplasia ◽  
Medical Center ◽  
Survival Rates ◽  
Patient Characteristics ◽  
University Hospital ◽  
Resolution Rate ◽  
Extremely Preterm ◽  
Postmenstrual Age ◽  
Preterm Born

ObjectiveTo determine the survival and evolution of pulmonary hypertension (PH) associated with bronchopulmonary dysplasia (BPD) in extremely premature born infants beyond 36 weeks postmenstrual age (PMA).DesignA single-centre retrospective cohort study from a university hospital.PatientsExtremely preterm (gestational age <30 weeks and/or birth weight <1000 g) infants, born between 2012 and 2017, in the University Medical Center Groningen with confirmed PH at/beyond 36 weeks PMA.Main outcome measuresSurvival, mortality rate and PH resolution. Patient characteristics, treatment, presence and evolution of PH were collected from patient charts.ResultsTwenty-eight infants were included. All had BPD, while 23 (82%) had severe BPD and 11 infants (39%) died. Survival rates at 1, 3 and 7 months from 36 weeks PMA were 89%, 70% and 58%, respectively. In 16 of the 17 surviving infants, PH resolved over time, with a resolution rate at 1 and 2 years corrected age of 47% and 79%, respectively. At 2.5 years corrected age, the resolution rate was 94%.ConclusionsThese extremely preterm born infants with PH-BPD had a survival rate of 58% at 6 months corrected age. Suprasystemic pulmonary artery pressure was associated with poor outcome. In the current study, infants surviving beyond the corrected age of 6 months showed excellent survival and resolution of PH in almost all cases. Prospective follow-up studies should investigate whether resolution of PH in these infants can be improved by multi-modal therapies, including respiratory, nutritional and cardiovascular treatments.

scholarly journals Care practices and outcomes of extremely preterm neonates born at 22–24 weeks –A single centre experience

2021 ◽  
pp. 1-8
Author(s):  
V.V. Ramaswamy ◽  
V.I. Oommen ◽  
A. Gupta ◽  
N. Weerapperuma ◽  
S. Zivanovic ◽  
...  
Keyword(s):  
Neonatal Intensive Care ◽  
Periventricular Leukomalacia ◽  
Survival Rates ◽  
Preterm Neonates ◽  
High Frequency Ventilation ◽  
Risk Of Death ◽  
Extremely Preterm ◽  
Frequency Ventilation ◽  
Level 3 ◽  
Care Practices

BACKGROUND: Wide variation in the care practices and survival rates of neonates born at peri-viable gestational ages of 22 +0 –24 +6 weeks exists. This study elucidates the postnatal risk factors for morbidity/mortality, contrasts the care practices and short-term outcomes of this vulnerable group of preterm neonates from a single center with others. METHODS: Retrospective study of neonates born at 22 +0 –24 +6 weeks in a level 3 neonatal intensive care unit in UK, over a period of 4 years (2016–2019). RESULTS: 94 neonates given active care studied. Survival until discharge was 51.1%(22–23 wks –44%, 24 wks –59.1%) and survival with no major brain injury (MBI) [grade III/IV IVH, cystic periventricular leukomalacia] was 38.3%(22–23 wks –32%, 24 wks –45.4%). Of those who survived until discharge, 75%had no MBI (22–23 wks –72.7%, 24 wks –76.9%). Neonates requiring significant respiratory support within first 72 hours as well as needing rescue high frequency ventilation had significantly high risk of mortality or MBI [aOR –7.17 (2.24–25.79), p = 0.00; 4.76 (1.43–20.00), p = 0.01]. CONCLUSIONS: Survival rate differed from other centres. MBI was low amongst survivors. Severe respiratory disease in the initial days was associated with a higher risk of death or MBI.

The effect of postnatal corticosteroids on growth parameters in infants with bronchopulmonary dysplasia

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Emma E. Williams ◽  
Theodore Dassios ◽  
Mikhaela Mann ◽  
Anne Greenough
Keyword(s):  
Preterm Infants ◽  
Bronchopulmonary Dysplasia ◽  
Head Circumference ◽  
Neonatal Intensive Care ◽  
Growth Parameters ◽  
Corticosteroid Treatment ◽  
Postnatal Growth ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
The Difference

Abstract Objectives Corticosteroids are administered to ventilator dependent infants with bronchopulmonary dysplasia (BPD) to improve respiratory function and facilitating extubation. Acutely, however, growth impairment can occur as a side effect of such therapy. We aimed to determine the effect of corticosteroids on postnatal growth during the entire neonatal intensive care unit (NICU) admission. Methods A whole population study of extremely preterm infants with BPD was undertaken. Corticosteroid therapy was classified as treatment with dexamethasone or hydrocortisone for a least five consecutive days. Growth was calculated as the difference in weight and head circumference z-score from birth to discharge. Results Six thousand, one hundred and four infants with BPD were included of whom 28.3% received postnatal corticosteroids. Infants receiving corticosteroids were less mature (GA 25.0 vs. 26.3 weeks) and of lower birthweight (0.70 vs. 0.84 kg) than those not receiving treatment. There were no significant differences between those who did and did not receive corticosteroids in weight gain (p=0.61) or head circumference growth (p=0.33) from birth to discharge. Single vs. multiple courses of postnatal corticosteroids did not result in significant differences in weight (p=0.62) or head circumference (p=0.13) growth. Conclusions Postnatal corticosteroid treatment did not affect the longer term growth of preterm infants with BPD.

scholarly journals Preventing Brain Injury in the Preterm Infant—Current Controversies and Potential Therapies

2021 ◽  
Vol 22 (4) ◽  
pp. 1671
Author(s):  
Nathanael Yates ◽  
Alistair J. Gunn ◽  
Laura Bennet ◽  
Simerdeep K. Dhillon ◽  
Joanne O. Davidson
Keyword(s):  
Cerebral Palsy ◽  
Brain Injury ◽  
Preterm Infant ◽  
Brain Damage ◽  
Preterm Infants ◽  
Preclinical Studies ◽  
Recombinant Erythropoietin ◽  
Neurological Outcomes ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

Preterm birth is associated with a high risk of morbidity and mortality including brain damage and cerebral palsy. The development of brain injury in the preterm infant may be influenced by many factors including perinatal asphyxia, infection/inflammation, chronic hypoxia and exposure to treatments such as mechanical ventilation and corticosteroids. There are currently very limited treatment options available. In clinical trials, magnesium sulfate has been associated with a small, significant reduction in the risk of cerebral palsy and gross motor dysfunction in early childhood but no effect on the combined outcome of death or disability, and longer-term follow up to date has not shown improved neurological outcomes in school-age children. Recombinant erythropoietin has shown neuroprotective potential in preclinical studies but two large randomized trials, in extremely preterm infants, of treatment started within 24 or 48 h of birth showed no effect on the risk of severe neurodevelopmental impairment or death at 2 years of age. Preclinical studies have highlighted a number of promising neuroprotective treatments, such as therapeutic hypothermia, melatonin, human amnion epithelial cells, umbilical cord blood and vitamin D supplementation, which may be useful at reducing brain damage in preterm infants. Moreover, refinements of clinical care of preterm infants have the potential to influence later neurological outcomes, including the administration of antenatal and postnatal corticosteroids and more accurate identification and targeted treatment of seizures.

scholarly journals The Association between early Gram-negative bacteria in tracheal aspirate cultures and severe bronchopulmonary dysplasia among extremely preterm infants requiring prolonged ventilation

2021 ◽  
Author(s):  
Yousuke Imanishi ◽  
Katsuya Hirata ◽  
Masatoshi Nozaki ◽  
Narutaka Mochizuki ◽  
Shinya Hirano ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Bronchopulmonary Dysplasia ◽  
Neonatal Intensive Care ◽  
Tracheal Aspirate ◽  
Multivariable Logistic Regression Analysis ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Postmenstrual Age

Objective: To evaluate the association between bronchopulmonary dysplasia (BPD) development at 36 weeks postmenstrual age (PMA) and Gram-negative bacteria in tracheal aspirate cultures among extremely preterm infants. Study Design: Retrospective cohort study. Patients were 155 infants aged less than or equal to 26 gestational weeks who were admitted to the neonatal intensive care unit of Osaka Women’s and Children’s Hospital from 2009 to 2018. Primary outcome was respiratory outcomes expressed as BPD development. Multivariable logistic regression analysis was used to identify neonatal and bacterial factors associated with BPD. Results: After adjusting for gestational age, birth weight, sex, chorioamnionitis, Gram-positive cocci (GPC) and Gram-negative rods (GNRs) in tracheal aspirate cultures within 28 days after birth, GNRs were significantly associated with BPD development (odds ratio [OR]: 3.88, 95% confidence interval [CI]: 1.68–8.94). In contrast, GPC were not associated with BPD development (OR: 0.47, 95% CI: 0.05–1.61). Conclusion: Gram-negative bacteria in tracheal cultures within 28 days of birth are associated with BPD development in infants aged less than or equal to 26 gestational weeks.

scholarly journals Effect of Antibiotic-induced Intestinal Dysbacteriosis on Bronchopulmonary Dysplasia and Related Mechanisms

2021 ◽  
Author(s):  
Xiao Ran ◽  
Yu He ◽  
Qing Ai ◽  
Yuan Shi
Keyword(s):  
Gut Microbiota ◽  
Bronchopulmonary Dysplasia ◽  
Neonatal Intensive Care ◽  
Macrophage Polarization ◽  
Survival Rates ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Inflammatory Reactions ◽  
Hyperoxia Exposure ◽  
Intestinal Dysbacteriosis

Abstract BackgroundThe modification of the gut microbiota by antibiotics may influence the disease susceptibility and immunological responses. Infants in the neonatal intensive care unit (NICU) subjected to frequent antibiotics and oxygen therapies, which may give rise to the local and systemic inflammatory reactions and progression of bronchopulmonary dysplasia (BPD). This study aimed to investigate the role of intestinal dysbacteriosis by antibiotic therapy before hyperoxia exposure in the progression of BPD.MethodsMice had been exposed to hyperoxia (85% O2) since postnatal day 3 until day 16 for the BPD model establishment, treated with antibiotics from postnatal day 2 until day 8. Treated mice and appropriate controls were harvested on postnatal day 10 for 16S rRNA gene sequencing, or postnatal day 17 for assessment of alveolar morphometry and macrophages differentiation.ResultsAntibiotic-induced intestinal dysbacteriosis before hyperoxia exposure gave rise to deterioration of BPD evidenced by reduced survival rates and alveolarization, moreover, antibiotic-induced intestinal dysbacteriosis resulted in increased iNOS and decreased Arg-1 levels in lung homogenates.ConclusionBroad-spectrum antibiotic-induced intestinal dysbacteriosis may participate in BPD pathogenesis via alteration of the macrophage polarization status. Manipulating the gut microbiota may potentially intervene the therapy of BPD.

Apgar Scoring: Its Use and Meaning for Today’s Newborn

2000 ◽  
Vol 19 (1) ◽  
pp. 17-19 ◽  
Author(s):  
Linda Juretschke
Keyword(s):  
Preterm Infant ◽  
Gestational Age ◽  
Apgar Score ◽  
Scoring System ◽  
Survival Rates ◽  
Age Groups ◽  
The Past ◽  
Extremely Preterm ◽  
Accepted Practice

Apgar scoring is a common and accepted practice used for evaluating newborns immediately after delivery. After its development by Dr. Virginia Apgar in the late 1940s/early 1950s, its use and meaning have evolved over the past five decades. Today, every baby born in a U.S. hospital is given an Apgar score. With advances in neonatology and improved survival rates for infants with lower gestational ages, a new or revised scoring system may be warranted in order to more appropriately evaluate the extremely preterm infant. In addition, the predictive capabilities of Apgar scoring must be considered with caution for all gestational age groups.

scholarly journals ARE CANADIAN NEONATOLOGISTS READY FOR A STEM CELL TRIAL FOR BRONCHOPULMONARY DYSPLASIA?

2018 ◽  
Vol 23 (suppl_1) ◽  
pp. e23-e23
Author(s):  
Mireille Guillot ◽  
Sarah Asad ◽  
Justin Presseau ◽  
Manoj M Lalu ◽  
Brigitte Lemyre ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Bronchopulmonary Dysplasia ◽  
Stem Cell Therapy ◽  
Barriers And Enablers ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Research Assistants

Abstract BACKGROUND Pre-clinical studies support the role of stem cells in preventing bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity. We are planning the first Canadian clinical trial of stem cell therapy for BPD. OBJECTIVES To ensure successful bench-to-bedside translation, the objective of our study was to identify the barriers and enablers that may influence neonatologists’ decision to identify extremely preterm infants at risk of BPD for participation in a stem cell trial for BPD. DESIGN/METHODS Semi-structured interviews were conducted with neonatologists across Canada. We used the Theoretical Domains Framework (TDF) to develop an interview topic guide covering 14 key domains that influence behavior (e.g. knowledge, intentions, goals, social influences). Two independent researchers used directed content analysis (using qualitative software NVIVO 11) to assign utterances to TDF thematic domains. We further identified sub-themes within domains to identify key barriers and enablers to neonatologists identifying infants for the planned trial. RESULTS Sixteen interviews were conducted with neonatologists across Canada (Western Canada n=7, Central Canada n=7, Eastern Canada n=2). Seven were practicing as a neonatologist for 10 years or less, 5 for 11–20 years and 4 for >20 years. Preliminary analyses demonstrated that neonatologists are eager to help identify patients for this study due to the importance they place on trying to treat BPD. Many participants had worries concerning the lack of evidence on long-term outcomes of stem cell therapy. Access to clear protocols, well defined eligibility criteria, and research assistants were brought up as key facilitators for screening patients. The most commonly reported barrier included the need for human resources (e.g. research assistants), funding, and institutional support to help screen patients. CONCLUSION Our interviews identified facilitators and barriers from a neonatologist perspective to a potential stem cells trial for BPD. Our findings will inform the design of a phase I/II clinical trial.

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