title: The influence of foetal prednisone exposure on the cortisol levels in the offspring.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Rheumatology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Florentien D O
authors.initials: FD
authors.lastname: de Steenwinkel
authors.forename: Anita C S
authors.initials: AC
authors.lastname: Hokken-Koelega
authors.forename: Johanna M W
authors.initials: JM
authors.lastname: Hazes
authors.forename: Radboud J E M
authors.initials: RJ
authors.lastname: Dolhain
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000503:physiopathology; D001794:Blood Pressure; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011241:Prednisone / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D011241:Prednisone; D006854:Hydrocortisone