title: Repeated courses of antenatal corticosteroids have adverse effects on aspects of brain development in naturally delivered baboon infants.
abstract: BACKGROUND
  Repeated courses of antenatal steroids in women at risk of preterm delivery have beneficial effects on lung maturation, but concern exists about the effects on brain development. We aimed to determine whether repeated courses of corticosteroids increased the risk of neuropathology as compared with single courses or no treatment.
  
  
  METHODS
  Single-course animals received a 6-mg dose of steroids at 123 and 124 d of gestation (dg; term, 185 dg; n = 6). Repeated-course animals received additional doses at 137 and 138 dg (n = 7). Controls received no steroids (n = 5). Baboons delivered naturally at term and necropsy was performed. Brains were assessed histologically for parameters of development and neuropathology.
  
  
  RESULTS
  Body weights did not differ between the groups (P > 0.05); neither did brain/body weight ratio. Density of glial fibrillary acidic protein (GFAP)-immunoreactive (IR) astrocytes in white matter (WM) was increased in the single- (P < 0.05) and repeated-course (P < 0.01) groups as compared with controls. Density of myelin basic protein (MBP)-IR oligodendrocytes was reduced in the repeated-course animals as compared with both the control and single-course groups (P < 0.05); oligodendrocyte transcription factor 2 (Olig2)-IR showed no difference between groups.
  
  
  CONCLUSIONS
  Repeated courses of antenatal corticosteroids have effects on myelination in the developing nonhuman primate brain, which should be taken into account when determining a dosing regimen.
authors.affiliation: Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Amy
authors.initials: A
authors.lastname: Shields
authors.forename: Merran
authors.initials: M
authors.lastname: Thomson
authors.forename: Vicki
authors.initials: V
authors.lastname: Winter
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Coalson
authors.forename: Sandra
authors.initials: S
authors.lastname: Rees
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000196:embryology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007273:Injections, Intramuscular; D023421:Models, Animal; D004676:Myelin Basic Protein / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D010215:Papio; D011247:Pregnancy
chemical_list: D000305:Adrenal Cortex Hormones; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein