Glucocorticoid exposure of sheep at 0.7 to 0.75 gestation augments late-gestation fetal stress responses

Objectives: Exposure to glucocorticoid levels inappropriately high for current maturation alters fetal hypothalamo-pituitary-adrenal axis (HPAA) development. In an established fetal sheep model, we determined whether clinical betamethasone doses used to accelerate fetal lung maturation have persistent effects on fetal HPAA hypotensive-stress responses. Study Design: Pregnant ewes received saline (n = 6) or betamethasone (n = 6); 2 × 110 μg/kg body weight doses injected 24 hours apart (106/107 and 112/113 days' gestational age, term 150 days). Basal adrenocorticotropin (ACTH) and cortisol and responses to fetal hypotension were measured before and 5 days after the first course and 14 days after the second course. Results: Basal ACTH and cortisol were similar with treatment. HPAA responses to hypotension increased after the second but not first course and ACTH/cortisol ratio increased indicating central HPAA effects. Conclusions: Results demonstrate latency in the emergence of fetal HPAA hyperresponsiveness following betamethasone exposure that may explain hyperresponsiveness in full-term but not preterm neonates.