Document Detail


Is prenatal glucocorticoid administration another origin of adult disease?
MedLine Citation:
PMID:  11703405     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. The intra-uterine environment is now believed to play a major role in the origin of many adult diseases. Illnesses in which there is significant 'programming' before the time of birth include hypertension, diabetes, coronary heart disease and stroke. Acting on a genetic predisposition, intra-uterine triggers appear to programme the individual's metabolism and endocrine milieu and, after birth, these risk factors are then either amplified or minimized by environmental influences. The triggers operative during fetal life that have been studied most extensively are undernutrition and glucocorticoid exposure. 2. Over the past decade, a series of studies in sheep have focused on the perinatal and life-long consequences of glucocorticoid exposure in mid- to late-pregnancy. These studies in the sheep model have shown that maternal injections with glucocorticoids, in a manner similar to clinical treatment for women at risk of preterm birth, enhance fetal lung maturation, but were also associated with developmental and other functional alterations that are of concern. With weekly doses to the mother, there is restricted fetal growth, delayed myelination of the central nervous system, altered blood pressure soon after birth and increased insulin response to glucose challenge in early adulthood. If the glucocorticoids are given to the fetus by ultrasound-guided intramuscular injection, rather than to the mother, the effects on lung maturation are similar, but growth is spared and blood pressure after birth is unaltered. Increased insulin response to glucose challenge occurs in early adulthood with glucocorticoid by either route and is independent of growth restriction. 3. The findings in experimental animals are supported by studies of children in the Western Australian Preterm Infant Follow-up Study. Multivariate analyses have shown that increasing the number of glucocorticoid exposures, for the purpose of enhancing lung maturation prior to preterm birth, is associated with reduced birthweight and behavioural disorders at 3 years of age. 4. The results of these animal and clinical studies provide further support for a role of prenatal glucocorticoid exposure in triggering predisposition to adult disease. Further exploration of these models is expected to uncover the mechanisms and lead to effective strategies that may underpin clinical interventions.
Authors:
J P Newnham
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  28     ISSN:  0305-1870     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-12     Completed Date:  2001-12-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  957-61     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia. jnewnham@obsgyn.uwa.edu.au
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MeSH Terms
Descriptor/Qualifier:
Adult
Animals
Betamethasone / pharmacology*
Female
Fetus / drug effects*,  embryology
Glucocorticoids / adverse effects*
Humans
Hypertension / chemically induced
Infant, Newborn
Models, Animal
Pregnancy
Pregnancy, Animal
Prenatal Exposure Delayed Effects*
Sheep
Grant Support
ID/Acronym/Agency:
R01 HL65397-01/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Glucocorticoids; 378-44-9/Betamethasone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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