The influence of foetal prednisone exposure on the cortisol levels in the offspring

Objective Pregnant women suffering from autoimmune disease use glucocorticoids. Glucocorticoids can partly diffuse to the foetus and may influence the development of the foetal hypothalamic-pituitary-adrenal axis, especially in early stage of pregnancy. The objective was to investigate whether prednisone exposure in utero influences the cortisol levels of the prepubertal children. Design Mothers participated in a prospective cohort study on rheumatoid arthritis (RA) and pregnancy. Children were exposed (n = 44) or nonexposed (n = 65) to prednisone in utero. Salivary cortisol levels were taken from all children during 1 day: at awakening, 30 min after awakening, 1 p.m. and bedtime. Cortisol levels between groups were also analysed using area under the curve (AUC), cortisol awakening response (CAR) and slope. Results The mean age (SD) of the children was 6·98 (1·23). The difference in mean (SD) cortisol level at '1 p.m.' was 5·42 nm (4·08) in the prednisone-exposed and 3·97 nm (4·00) in the nonexposed (P = 0·03). Prednisone-exposed children had a higher AUC (β = 13·28; P = 0·02), even after correction for RA disease activity. No differences were found on CAR, slope or blood pressure. The cortisol levels of the nonexposed were more similar to the age-specific references than the prednisone-exposed. Conclusion Prednisone use during pregnancy is associated with a higher daytime cortisol level, in the prepubertal offspring, not yet accompanied with clinical outcomes. This conclusion will have no consequences at this moment, but it does raise questions concerning prednisone exposure in utero and the long-term consequences for the offspring.

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