Research overview
A single course of antenatal steroid (ANS) therapy is standard of care for women at risk of imminent preterm birth between 24-34 weeks’ gestation. Dosing regimens vary widely between different regions but generally involve the maternal intramuscular administration of 24 mg of either dexamethasone phosphate or betamethasone phosphate (with or without betamethasone acetate) in divided doses over a 24-48h period.
Well-targeted ANS therapy reduces the incidence of neonatal respiratory distress syndrome as well as several neonatal morbidities and mortality. An important but unresolved challenge relates to the potential risk for adverse long-term effects arising from ANS therapy, and how these potential risks might be balanced with therapeutic benefit in a target population.
Areas covered:
We provide a detailed assessment of the animal and human antenatal steroid literature. We first introduce key concepts in glucocorticoid signalling, steroid pharmacokinetics and pharmacodynamics, and clinical use before moving to present human and animal data to inform the potential for long-term harms arising from antenatal steroid therapy.
Expert opinion:
Following a review of the literature, our assessment is that:
1) antenatal exposure to the high doses of betamethasone or dexamethasone in current clinical use does have the potential to induce a range of multi-system changes in the mammalian (including human) fetus that alter growth and maturational development in a manner that may increase long-term risk of diseases (notably neurological and endocrine); and
2) these risks are likely to increase in proportion to the magnitude and duration of steroid exposure.
We conclude that giving a single course of ANS therapy to women between 24 and 34 weeks of pregnancy, who are carefully assessed and at risk of preterm labour, is well justified. However, efforts should be made to improve dosing and patient selection to enhance the risk-benefit balance.
For ANS use outside this age range (excluding resource-poor settings), the risk-benefit discussion is more complex. At periviable gestations, the high immediate risk of active treatment justifies accepting modest long-term risks. At late preterm and term gestations, where steroids do not provide significant survival or health benefits, it is more difficult to support the routine ANS use.
Project researchers
Dr Sean Carter
Ms Erin Fee
Ms Hannah Watson
Professor Matt Kemp
Partners
Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Department of Neonatology, Khoo-Teck Puat National University Children’s Medical Institute, National University Hospital, Singapore
Division of Obstetrics and Gynaecology, University of Western Australia, Australia.
Centre for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan.
Division of Pulmonary Biology, Cincinnati Children’s Hospital, Cincinnati, OH.
Department of Obstetrics and Gynecology, Faculty of Medicine, Universidad de los Andes, Santiago, Chile.
IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile.
Project timeline
Completed 2025
Publication
Addressing the long-term risks of administering antenatal steroids
