Date of Award
Doctor of Philosophy (PhD)
Professor S.A. Atkinson
Dexamethasone (DEX) treatment in very preterm infants has proven to facilitate earlier weaning from mechanical ventilation and supplemental oxygen, thereby lessening the severity of lung disease incurred by long-term oxygen dependency. However, DEX therapy is not without negative side-effects; studies in preterm infants and piglets have reported DEX-induced impairments in growth and bone mineral metabolism. DEX may act by altering the concentration or activity of specific components of the growth hormone (GH)/insulin-like growth factor (IGF-I) axis which are essential for regulating growth and bone mass. The first study, in preterm infants, characterized how DEX alters the circulating components of the GH-IGF-I axis and suggested potential mechanisms by which DEX delays growth and bone development as both plasma IGF-I and biochemical markers of bone metabolism were reduced during DEX. The objectives of the piglet studies were to delineate the effectiveness of adjunctive GH or GH+IGF-I to counter the detrimental effects of DEX on growth, protein turnover and bone mass. In the first studies, we administered GH, GH+IGF-I or placebo to piglets while they received a two week course of DEX. GH and GH+IGF-I partially attenuated the reductions in growth and bone mas to a similar extent. Only with respect to protein metabolism was an additional benefit observed with combined treatment (GH+IGF-I). A dose-response study revealed the minimal effective GH dose, and demonstrated that bone cell activity and weight and length gain returned to control levels during a period of rehabilitation in which no DEX or GH were administered. Currently, it is uncertain if DEX-treated infants experience similar metabolic improvements in weight and length growth or bone mineral mass post-DEX treatment or whether the metabolic insults of DEX are sustained. Longer term follow-up of DEX-treated preterm infants is required to fully comprehend to long-term consequences of DEX on growth into childhood. If there are long-term effects on growth and bone development, future studies should focus on whether GH is more effective post-DEX compared to during DEX treatment or whether adjunctive administration of other anabolic agents will counter the negative effects of DEX during development.
Ward, Wendy Elizabeth, "Steroid-induced growth delay and bone abnormalities in preterm infants and piglets during early development: the interaction of steroids and the GH-IGF-I axis" (1998). Open Access Dissertations and Theses. Paper 2060.