Optimizing antenatal corticosteroid therapy: Balancing benefit and risk in the era of precision medicine

Antenatal corticosteroid (ACS) therapy is a cornerstone of modern perinatal care and remains an effective intervention for reducing neonatal morbidity and mortality associated with preterm birth. However, emerging evidence highlights the need for a more refined approach to ACS use, especially with contemporary expansion of the ACS therapy eligible population. A relatively small pool of evidence exists for several sub-populations exposed to ACS therapy, including multiple pregnancies, intrauterine growth restriction and in the setting of chorioamnionitis. This review synthesized current evidence on the pharmacokinetics, efficacy, and safety of ACS, with particular focus on dose optimization, long-term outcomes, and variability in fetal treatment response. We examined the potential of developing tools to assess fetal lung maturation and thus pregnancies that would most benefit from ACS therapy. Additionally, we sought to address emerging concerns regarding ACS overexposure and unintended effects on non-pulmonary fetal systems. The review highlights key knowledge gaps, particularly in relation to long-term neurodevelopmental outcomes, optimal dosing strategies, and tools for individualized risk prediction. Development of precision-based approaches to ACS therapy is essential to ensure maximal benefit and minimal harm across varied clinical contexts in which this intervention is used.