Article

Repeated courses of antenatal corticosteroids have adverse effects on aspects of brain development in naturally delivered baboon infants.

Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, Victoria, Australia.
Pediatric Research (Impact Factor: 2.84). 02/2012; 71(6):661-7. DOI: 10.1038/pr.2012.18
Source: PubMed

ABSTRACT 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.
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.
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.
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.

0 Bookmarks
 · 
74 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Various neurological and psychiatric manifestations have been recorded in children with adrenal disorders. Based on literature review and on personal case-studies and case-series we focused on the pathophysiological and clinical implications of glucocorticoid-related, mineralcorticoid-related, and catecholamine-related paediatric nervous system involvement. Childhood Cushing syndrome can be associated with long-lasting cognitive deficits and abnormal behaviour, even after resolution of the hypercortisolism. Exposure to excessive replacement of exogenous glucocorticoids in the paediatric age group (e.g., during treatments for adrenal insufficiency) has been reported with neurological and magnetic resonance imaging (MRI) abnormalities (e.g., delayed myelination and brain atrophy) due to potential corticosteroid-related myelin damage in the developing brain and the possible impairment of limbic system ontogenesis. Idiopathic intracranial hypertension (IIH), a disorder of unclear pathophysiology characterised by increased cerebrospinal fluid (CSF) pressure, has been described in children with hypercortisolism, adrenal insufficiency, and hyperaldosteronism, reflecting the potential underlying involvement of the adrenal-brain axis in the regulation of CSF pressure homeostasis. Arterial hypertension caused by paediatric adenomas or tumours of the adrenal cortex or medulla has been associated with various hypertension-related neurological manifestations. The development and maturation of the central nervous system (CNS) through childhood is tightly regulated by intrinsic, paracrine, endocrine, and external modulators, and perturbations in any of these factors, including those related to adrenal hormone imbalance, could result in consequences that affect the structure and function of the paediatric brain. Animal experiments and clinical studies demonstrated that the developing (i.e., paediatric) CNS seems to be particularly vulnerable to alterations induced by adrenal disorders and/or supraphysiological doses of corticosteroids. Physicians should be aware of potential neurological manifestations in children with adrenal dysfunction to achieve better prevention and timely diagnosis and treatment of these disorders. Further studies are needed to explore the potential neurological, cognitive, and psychiatric long-term consequences of high doses of prolonged corticosteroid administration in childhood.
    International Journal of Endocrinology 01/2014; 2014:282489. · 1.52 Impact Factor
  • Neural Regeneration Research 05/2014; 9(9):909-11. · 0.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To determine the impact of prenatal exposure to maternal anti-Ro antibodies, slow fetal heart rate and/or chronic dexamethasone therapy for immune-mediated congenital atrio-ventricular heart block (CAVB) on cognitive and academic performance at school age.Methods: Prospective, blinded assessment of cognitive functioning of 3 cohorts of children aged 6-16 years with in-utero exposure to maternal anti-Ro antibodies and with: 1) no CAVB and no prenatal dexamethasone (n=14); 2) CAVB without prenatal treatment (n=10); and 3) CAVB with prenatal dexamethasone therapy (n=16). Domains assessed included intelligence, visual perceptual and visual motor skills, auditory and visual attention, verbal learning and memory, visual memory, executive function and behavior.Results: All cohorts scored within the normal range and were not significantly different in intelligence scores, verbal comprehension, perceptional reasoning, working memory, and processing speed. For prenatally treated children with CAVB, there were no significant associations between neurocognitive function scores, minimal fetal heart rate (range: 47 – 80 beats/min) and the duration and dosage (2-15 weeks; 56 – 824 mg) of dexamethasone therapy.Conclusion: CAVB and transplacental prenatal treatment with dexamethasone was not associated with neurocognitive impairment in school-age children. Larger numbers are required to validate our observation and assessment of other cognitive abilities is warranted. © 2014 American College of Rheumatology.
    Arthritis & Rheumatology. 04/2014; 66(8).

Full-text (2 Sources)

Download
19 Downloads
Available from
Jun 10, 2014