The Story of Antenatal Steroid Therapy before Preterm Birth

Hallman, Mikko

doi:10.1159/000381130

Cited by 16 publications

(8 citation statements)

References 28 publications

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“…Research studies using biochemical, physiological, or molecular genetic techniques, and cell culture or experimental animal models, have informed, for example, the development of antenatal corticosteroid therapy, exogenous surfactant administration, nitric oxide treatment for respiratory failure, and therapeutic hypothermia for neonatal encephalopathy [7-10]. …”

Section: Early-stage Translational Researchmentioning

confidence: 99%

The Research Cycle: Improving Care and Outcomes for Newborn Infants

McGuire

Halliday

2018

Neonatology

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Ensuring that policies and practice in perinatal care are informed by evidence from high-quality research is fundamental to improving outcomes for newborn infants and their families. Effective interventions in the perinatal period can have a life-long impact disproportionate to their costs. Many of the major advances in care that have transformed outcomes for preterm and sick newborn infants have been informed by empirical and applied health research. Conversely, there are examples of life-long adverse consequences for infants and families that are a legacy of practices based on poor-quality evidence. The challenge in the 21st century is to maintain the trajectory of improvements in care and outcomes. This will most likely be achieved via marginal gains from new or improved care practices underpinned by a range of research approaches, from preclinical and laboratory-based empirical studies that uncover pathogenic pathways or therapeutic mechanisms, to large-scale, applied research such as multicentre, randomised controlled trials. This will involve the coordination and collaboration of research efforts globally. Strategies to develop and prioritise research questions need to involve parents and families. Given the context in which much perinatal research is conducted, particularly in emergency situations around the time of birth, robust and transparent ethics and governance frameworks are essential to maintain the trust and engagement of communities. An ethical imperative exists to ensure that research output is disseminated effectively, and that effective and cost-effective interventions are implemented and integrated within a cycle that audits and benchmarks good practice and outcomes, and informs research evidence-based continuous quality improvement. This is the first in a series of articles on research methodology in neonatal medicine to be published in Neonatology, in response to a request from trainee researchers. We introduce the series by describing the research cycle, in particular how it is applied in neonatal medicine. Subsequent articles will cover translational research, clinical trials, diagnostic tests, global challenges, and the ethical issues relating to neonatal/perinatal research.

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Section: Early-stage Translational Researchmentioning

confidence: 99%

The Research Cycle: Improving Care and Outcomes for Newborn Infants

McGuire

Halliday

2018

Neonatology

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“…In den frühen 1990er Jahren wurden mit der Entwicklung neuer Beatmungsmethoden, der routinemäßigen Einführung der pränatalen Lungenreifungsinduktion durch Kortikosteroide und der Surfactant-Ersatztherapie wesentliche Fortschritte in der Perinatologie erreicht (sog. "Surfactant-Ära") [19][20][21]. Die "neue" BPD der Surfactant-Ära -definiert als zusätzlicher Sauerstoffbedarf im Alter von 28 Tagen und klassifiziert nach dem Sauerstoffbedarf im Alter von 36 Wochen post menstruationem -zeigt sich mit veränderter Pathophysiologie: Nicht die Schädigung bereits entwickelter Lungenstrukturen steht im Vordergrund, sondern der Stillstand der physiologischen Lungenentwicklung mit gestörter alveolärer und vaskulärer Struktur [22,23].…”

Section: Einleitung ▼unclassified

Lungenfunktion in Kindheit und Adoleszentenalter: Einfluss von Frühgeburtlichkeit und bronchopulmonaler Dysplasie

Segerer

Speer

2016

Z Geburtshilfe Neonatol

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“…1 To prevent preterm labor or to improve its outcome, pregnant women may receive a variety of medications daily, 2,3 such as steroids like betamethasone (BTM) or dexamethasone (DXM), which have been shown to decrease neonatal morbidity and mortality. [4][5][6] Especially the administration of prenatal BTM or DXM induces the immature pulmonary surfactant system of preterm infants, thereby reducing frequency and intensity of respiratory distress syndrome (RDS). 6 Administration of maternal progesterone has been also demonstrated to be beneficial in reducing primary and recurrent preterm birth.…”

Section: Introductionmentioning

confidence: 99%

Progesterone Antagonizes Dexamethasone-Regulated Surfactant Proteins In Vitro

Kunzmann

Ottensmeier²,

Speer³

et al. 2018

Reprod Sci

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Pregnant women at risk of preterm labor routinely receive glucocorticoids (GCs) and frequently also progesterone. Administration of GCs accelerates intrauterine surfactant synthesis and lung maturation, thereby reducing the incidence of neonatal respiratory distress syndrome; progesterone has the potential to prevent preterm birth. Little is known about possible interactions of GCs and progesterone. Our aim was to clarify whether progesterone can affect dexamethasone (DXM)-regulated expression of surfactant protein A (SP-A), SP-B, and SP-D in lung epithelial cells. H441 cells were exposed to DXM and progesterone and expression of SPs was analyzed by quantitative real-time polymerase chain reaction and immunoblotting. Although progesterone had no direct effect on the expression of SP-B, DXM-mediated induction was inhibited dose dependently on the transcriptional (64 µM [ P < .0001], 32 µM [ P = .0005], 16 µM [ P = .0019]) and the translational level. Furthermore, progesterone inhibited stimulatory effects of other GCs as well. While exogenous tissue growth factor β1 (TGF-β1) inhibited DXM-induced SP-B expression (messenger RNA [mRNA]: P = .0014), progesterone itself did not influence TGF-β1 mRNA expression and/or TGF-β1/Smad signaling, demonstrating that TGF-β1 and/or Smad activation is not involved. The inhibitory effect of progesterone could be imitated by the GC and progesterone receptor (PR) antagonist RU-486, but not by the specific PR antagonist PF-02413873, indicating that progesterone acts as a competitive antagonist of DXM. The effect of progesterone on DXM-regulated genes was not specific for SP-B, as expression of SP-A and SP-D mRNAs was also antagonized. The present study highlights a new action of progesterone as a potential physiological inhibitor of GC-dependent SP expression in lung epithelial cells. The clinical relevance of this in vitro finding is currently unknown.

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The Story of Antenatal Steroid Therapy before Preterm Birth

Cited by 16 publications

References 28 publications

The Research Cycle: Improving Care and Outcomes for Newborn Infants

The Research Cycle: Improving Care and Outcomes for Newborn Infants

Lungenfunktion in Kindheit und Adoleszentenalter: Einfluss von Frühgeburtlichkeit und bronchopulmonaler Dysplasie

Progesterone Antagonizes Dexamethasone-Regulated Surfactant Proteins In Vitro

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