Growth restriction in dexamethasone-treated preterm infants may be mediated by reduced IGF-I and IGFBP-3 plasma concentrations

OBJECTIVE Preterm infants receiving dexamethasone for respiratory morbidity frequently suffer restricted growth. The aim of this study was to investigate the interactions between dexamethasone treatment regimen and circulating IGFBP-3 and IGF-I levels, and the associations between these variables and linear growth rate in preterm babies receiving dexamethasone for chronic lung disease of prematurity. DESIGN A randomised, unblinded, clinical trial of two different courses of dexamethasone: a 42-day tapering course (the long course) and a repeatable 3 day pulse course. PATIENTS Forty preterm infants (19 in the pulse group, 21 in the long group) with a birthweight less than or equal to 1250 g who were ventilated at 7 days of age. MEASUREMENTS Lower leg length was measured thrice weekly by knemometry, and IGFBP-3 and IGF-I levels were measured prior to commencing treatment, at 14 and 42 days of treatment and at 36 weeks postmenstrual age (PMA). Interactions between variables were analysed by stepwise regression analysis and analysis of covariance (ancova). Associations between variables were assessed by correlation coefficients. RESULTS In an ancova, mean daily dose of dexamethasone/kg (MDDD) and treatment group both significantly influenced IGFBP-3 levels (P = 0.0009 and P = 0.017, respectively), and tended to influence IGF-I levels similarly (P = 0.098 and P = 0.07). MDDD also significantly influenced mean daily increase in lower leg length (MDILL; P < 0.01). IGFBP-3 and IGF-I levels were significantly related to MDILL (ancova: P < 0.01). The correlation coefficients for IGFBP-3 and IGF-I levels and MDILL were 0.2 and 0.3 (both P < 0.0001), respectively. IGFBP-3 and IGF-I levels were highly correlated (r(2) = 0.52, P < 0.0001) and both increased significantly with increasing PMA (P < 0.0001). IGF-I levels were higher in females (P = 0.036). CONCLUSION This study provides evidence that the growth-restricting effects of dexamethasone may be mediated, at least in part, via suppression of the IGF axis. Both dexamethasone dose and treatment regimen influence circulating IGF-I and IGFBP-3 levels, and both are important in inducing growth restriction.