title: Reduced life expectancy in rats after neonatal dexamethasone treatment.
abstract: The glucocorticoid dexamethasone (Dex) is widely used in preterm infants for the prevention of chronic lung disease. However, major concern has arisen about the long-term sequelae of this therapy. Here we report that neonatal treatment with dexamethasone significantly shortens the lifespan by 25% of male rats (28.6 +/- 1.1 to 21.3 +/- 0.8 mo) and by 18% of female rats (26.9 +/- 1.8 to 22.0 +/- 0.7 mo). Histopathological examination indicated end-stage cardiac and renal failure as the cause of premature death. Furthermore, Dex-treated rats showed symptoms of hypertension at young adult age, which worsened with increasing age. Thus, a brief period of glucocorticoid treatment during early life results in untimely death presumably due to cardiovascular and renal disease later in life. These serious, adverse long-term consequences call for prudence with glucocorticoid treatment of human preterm infants and careful follow-up of young adults with a history of neonatal glucocorticoid treatment.
authors.affiliation: Department of Pharmacology and Anatomy, Rudolph Magnus Institute of Neuroscience, 3508 AB Utrecht, The Netherlands.
authors.forename: Patrick J G H
authors.initials: PJ
authors.lastname: Kamphuis
authors.forename: Willem B
authors.initials: WB
authors.lastname: de Vries
authors.forename: Joost M
authors.initials: JM
authors.lastname: Bakker
authors.forename: Annemieke
authors.initials: A
authors.lastname: Kavelaars
authors.forename: Jaap E
authors.initials: JE
authors.lastname: van Dijk
authors.forename: Marguerite E
authors.initials: ME
authors.lastname: Schipper
authors.forename: Matthijs F M
authors.initials: MF
authors.lastname: van Oosterhout
authors.forename: Gerda
authors.initials: G
authors.lastname: Croiset
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
authors.forename: Frank
authors.initials: F
authors.lastname: van Bel
authors.forename: Victor M
authors.initials: VM
authors.lastname: Wiegant
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology; D008017:Life Expectancy; D008136:Longevity / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone