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New approaches to hormonal acceleration of fetal lung maturation
J C Schellenberg1, G C Liggins
1Postgraduate School of Obstetrics and Gynecology, National Women's Hospital, Auckland, New Zealand.
Insights
Antenatal glucocorticoid therapy effectively reduces respiratory distress syndrome (RDS) in premature infants. However, efficacy decreases with lower gestational age, prompting research into combined hormone treatments for enhanced fetal lung maturation.
Area of Science:
- Perinatology
- Neonatology
- Developmental Biology
Background:
- Antenatal glucocorticoid administration is a cornerstone therapy for preventing and treating respiratory distress syndrome (RDS) in premature infants.
- Established protocols aim to mimic physiological glucocorticoid levels, demonstrating significant reductions in RDS incidence and severity.
- Long-term follow-up studies indicate a low likelihood of adverse developmental effects in children exposed to antenatal glucocorticoids.
Purpose of the Study:
- To review the established effects of glucocorticoids on fetal lung maturation in both animal models and human subjects.
- To present recent findings from the author's laboratory regarding factors influencing glucocorticoid efficacy.
- To explore novel therapeutic strategies for improving fetal lung maturation, particularly in cases of limited response to conventional treatment.
Main Methods:
- Review of existing literature on glucocorticoid effects on lung maturation.
- Presentation of experimental data from the author's laboratory, including studies in fetal sheep.
- Investigation of combined hormone therapies, including cortisol, triiodothyronine, prolactin, and thyrotropin-releasing hormone (TRH).
Main Results:
- Antenatal glucocorticoids are effective in reducing RDS, with therapeutic levels comparable to those in newborns experiencing RDS or prolonged membrane rupture.
- A subset of fetuses, especially those below 28 weeks gestation, exhibit a diminished response to glucocorticoid therapy.
- In fetal sheep, glucocorticoid efficacy for lung maturation decreases with advancing gestational age; however, combined administration of cortisol, triiodothyronine, and prolactin, or TRH and cortisol, promoted lung maturation.
Conclusions:
- While antenatal glucocorticoids are beneficial, their efficacy is variable and reduced in very preterm fetuses.
- Combined hormone therapies, such as glucocorticoids with TRH, show promise in enhancing fetal lung maturation and warrant further investigation in human trials.
- Optimizing antenatal treatment strategies is crucial for improving outcomes in extremely premature infants.
Abstract:
The paper reviews the effects on lung maturation of glucocorticoids in animals and humans and presents relevant recent findings from the author's laboratory. It is now well established that antenatal glucocorticoid treatment reduces the incidence and severity of the respiratory distress syndrome (RDS) in prematurely born infants. The recommended doses of glucocorticoids produce fetal glucocorticoid activity levels similar to those of newborns with RDS or prolonged rupture of the membranes. Extensive follow-up studies have shown that adverse effects on child development are unlikely to occur. It is also evident that a significant number of fetuses do not respond to the treatment, which is of particular consequence in fetuses of less than 28 weeks gestation. These fetuses are less likely to respond to glucocorticoid therapy that fetuses between 28 and 32 weeks gestation and are at a higher risk of developing complications due to their immaturity. In fetal sheep, there is a similar decrease in the efficacy of glucocorticoids on lung maturation with decreasing gestational age. Simultaneous infusion of cortisol, triiodothyronine and prolactin but not of any of these hormones administered singly or in combination of two produced mature lungs in fetal sheep of 125 days gestation. Similar results were obtained with thyrotropin releasing hormone (TRH) and cortisol. It remains to be seen whether the combined administration of glucocorticoids and TRH accelerates lung maturation in human fetuses.