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

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 mass 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 the 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.