Research overview
Worldwide, 15 million babies are born preterm (<37 weeks’ gestation) annually, placing them at increased risk of neonatal death, and lifelong disability. To reduce these risks, women at risk of preterm birth are routinely administered antenatal glucocorticoids (ACS) which activate the fetal glucocorticoid receptor (GR), accelerating fetal lung maturation and improving neonatal survival.
However, there is considerable variability in ACS efficacy, with a large proportion of babies failing to demonstrate respiratory benefit from treatment. A critical gap in current knowledge is understanding the biological basis of this sizable variability in fetal response to ACS. Why do current clinical regimens fail to uniformly induce fetal lung maturation?
ACS dosing is uniform, despite sizable evidence showing inter-individual variability in glucocorticoid responses to agonist stimulation. Data from this research group strongly suggest that there is a heritable component to fetal ACS responsiveness, and that lower doses of ACS more reliably induce lung maturation, suggesting that current doses may exceed the optimal range for GR activation in many individuals. This project seeks to understand the role of individual responses to ACS dose in relation to fetal lung maturation, with a view to inform optimised (and potentially precision) ACS dosing.
The team will employ an ex-vivo fetal lung explant model allowing them to test individual ACS sensitivity profiles and identify inter-individual variability, while preserving the native tissue architecture.
This project addresses a fundamental gap in the understanding of ACS-driven lung maturation. Until we can define the optimal dose range and understand differential response profiles to ACS, our ability to optimise ACS and improve outcomes remains limited.
By identifying dose-response relationships, this research will inform safer, more individualised antenatal care for mothers and babies. This approach aims to reduce unnecessary exposure and potential harm, while extending the benefits of ACS therapy to fetuses who currently do not respond.
Project researchers
Hannah Watson
Funders
Women and Infants Research Foundation
Project timeline
2026 – 2027
