Research overview
Antenatal steroids (ANS) are an essential part of the obstetric management of women at risk of preterm delivery, and are estimated to be administered to between 8 and 15% of all WA mothers and babies.
ANS have been proven to reduce the risk of neonatal mortality and morbidity, however current dosing practices, which use the mother as a reservoir, see the mother and fetus exposed to unnecessarily high doses of steroid that disrupt the maternal and fetal hypothalamic pituitary axis (HPA), alter placental transfer and glucose regulation, something particularly problematic for the increasing numbers of women with gestational diabetes. Recent studies have linked steroid exposures to increased risk of long-term harms including abnormal brain development associated with childhood learning difficulties, insulin resistance and precursors for adult disease such as obesity and diabetes.
Additional studies have shown that higher ANS doses do not convey benefit. Our group has previously shown that a fetal plasma betamethasone concentration of 2ng/ml (one tenth achieved with maternal reservoir dosing) achieves lung maturation equivalent to that of a standard, high-dose antenatal steroid regimen.
This research will generate pre-clinical data necessary to develop a targeted, low-dose ANS therapy that is delivered via nanoparticles exclusively to the fetus. This treatment approach will achieve life-saving maturation of the preterm lung, whilst shielding the mother and placenta from high-dose steroid exposures seen in current ANS dosing strategies.
Why this project is important
The study will address optimisation of ANS therapy in order to save lives and reduce the risk of long-term disease for preterm babies. Preterm birth is WA’s leading cause of neonatal death, with the majority of these deaths being related to respiratory complications. Development of a targeted, low dose ANS treatment regimen is now increasingly viewed as critical to the improvement of ANS treatment efficacy and safety. In using nanoparticles to develop a low dose ANS therapy targeted to the fetus, we can significantly decrease maternal and fetal steroid exposures, reducing the risk of harm to mother and fetus. In addition to improving immediate treatment benefit and enhanced safety for preterm babies and mothers, such an approach may also improve the overall risk profile of ANS therapy. This is because in many centres, ANS are often incorrectly administered to women who go on to deliver at term. In these cases, the adverse off-target effects on maternal glucose control, and on placental function manifest as reduced fetal growth and greater risk of childhood learning deficits and poor executive function. Although accurate targeting of treatments is the optimal solution, a reduced dose ANS treatment that uses nanoparticles to limit steroid exposure to the fetus has the potential to greatly improve outcomes for the very sizable number of mothers and babies that receive off-target treatments.
Project researchers
Erin Fee
Professor Matt Kemp
Partners
Tohoku University Hospital, Sendai Japan
National University of Singapore
The University of Western Australia
Funders
Channel 7 Telethon Trust
Project timeline
2023 – current
