Addressing the long-term risks of administering antenatal steroids

Introduction: A single course of antenatal steroid (ANS) therapy is standard of care for women at risk of preterm birth, reducing the risk of neonatal respiratory distress syndrome, neonatal morbidity, and mortality. An unresolved challenge relates to the potential risk of adverse long-term effects, and how these risks might be balanced with therapeutic benefit. Areas covered: We outline key concepts in glucocorticoid signaling, pharmacokinetics/pharmacodynamics, and clinical use before presenting data on the potential long-term harms of ANS therapy. Expert opinion: Our assessment is that: i) Currently used, high dose ANS regimens can induce multi-system changes in the fetus that alter growth and development, potentially increasing long-term disease risk; and ii) relative risks likely increase proportionally to the magnitude and duration of steroid exposure, in late preterm and term ANS use, and in off-target treatments. A single course of ANS therapy to at risk women between 24- and 34-weeks' gestation is well justified. Efforts should be made to improve dosing and patient selection. At periviable gestations, the high immediate risk of serious disease or death justifies modest long-term risks. At late preterm and term gestations, where steroids do not provide notable survival or health benefits, supporting routine ANS use is more difficult.