Reduced life expectancy in rats after neonatal dexamethasone treatment.
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.
Kamphuis
Patrick J G H
PJ
Department of Pharmacology and Anatomy, Rudolph Magnus Institute of Neuroscience, 3508 AB Utrecht, The Netherlands.
de Vries
Willem B
WB
Bakker
Joost M
JM
Kavelaars
Annemieke
A
van Dijk
Jaap E
JE
Schipper
Marguerite E
ME
van Oosterhout
Matthijs F M
MF
Croiset
Gerda
G
Heijnen
Cobi J
CJ
van Bel
Frank
F
Wiegant
Victor M
VM
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
D005938:Glucocorticoids; D003907:Dexamethasone