Antenatal steroids (ANS) are one of the most widely prescribed medications in pregnancy, being administered to women at risk of preterm delivery. In the setting of preterm delivery at or below 35 weeks’ gestation, systematic review data show ANS reduce perinatal morbidity and mortality, primarily by promoting fetal lung maturation. However, with the expanding use of this intervention has come a growing appreciation for the potential off-target, adverse effects of ANS therapy on wider fetal development. We undertook a narrative literature review of the animal and clinical literature to assess current evidence for adverse effects of ANS exposure and fetal development. This review presents a summary of the evidence relating to the potential for wide-ranging, off-target, adverse effects of ANS therapy on fetal development and programming. We highlight an urgent need for further animal and clinical studies investigating the effects of ANS on the fetal immune, cardiovascular, renal and hepatic systems given a current sparsity of evidence. We also strongly suggest an emphasis on open disclosure, discussion and education of clinicians and patients with regard to the potential benefits and risks of ANS therapy, particularly in late preterm and term gestations where infants derive relatively few benefits from these drugs. We also propose further studies on the optimisation of ANS therapy through improved patient selection and improved dosing regimens based on a pharmacokinetic-pharmacodynamic informed understanding of ANS action on the fetal lung.

Antenatal corticosteroids are used to augment fetal lung maturity in human pregnancy. Dexamethasone (DEX) is also used to treat congenital adrenal hyperplasia of the fetus in early pregnancy. We previously reported effects of synthetic corticosteroids given to sheep in early or late gestation on pregnancy length and fetal cortisol levels and glucocorticoids alter plasma insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) concentrations in late pregnancy and reduce fetal weight. The effects of administering DEX in early pregnancy on fetal organ weights and betamethasone (BET) given in late gestation on weights of fetal brain regions or organ development have not been reported. We hypothesized that BET or DEX administration at either stage of pregnancy would have deleterious effects on fetal development and associated hormones. In early pregnancy, DEX was administered as four injections at 12-hourly intervals over 48 h commencing at 40–42 days of gestation (dG). There was no consistent effect on fetal weight, or individual fetal organ weights, except in females at 7 months postnatal age. When BET was administered at 104, 111 and 118 dG, the previously reported reduction in total fetal weight was associated with significant reductions in weights of fetal brain, cerebellum, heart, kidney and liver. Fetal plasma insulin, leptin and triiodothyronine were also reduced at different times in fetal and postnatal life. We conclude that at the amounts given, the sheep fetus is sensitive to maternal administration of synthetic glucocorticoid in late gestation, with effects on growth and metabolic hormones that may persist into postnatal life.