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Growth restriction in dexamethasone-treated preterm infants may be mediated by reduced IGF-I and IGFBP-3 plasma
F H Bloomfield1, D B Knight, B H Breier
1Research Centre for Developmental Medicine and Biology, University of Auckland, New Zealand.
Insights
Dexamethasone treatment for preterm infants with lung disease can restrict growth by suppressing the Insulin-like Growth Factor (IGF) axis. Both the dose and regimen of dexamethasone impact IGF levels and infant growth.
Area of Science:
- Neonatal Medicine
- Pediatric Endocrinology
- Pharmacology
Background:
- Dexamethasone is used to treat respiratory morbidity in preterm infants.
- This treatment is associated with restricted growth in these vulnerable infants.
Purpose of the Study:
- To investigate how dexamethasone treatment regimens interact with Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) and Insulin-like Growth Factor I (IGF-I) levels.
- To determine the association between these factors and linear growth rate in preterm infants.
Main Methods:
- A randomized clinical trial comparing a 42-day tapering dexamethasone course with a 3-day pulse course.
- Measured lower leg length by knemometry and IGFBP-3/IGF-I levels in 40 preterm infants.
- Analyzed data using stepwise regression and ANCOVA.
Main Results:
- Dexamethasone dose and treatment group influenced IGFBP-3 and IGF-I levels.
- Mean daily dexamethasone dose significantly affected linear growth rate.
- IGFBP-3 and IGF-I levels were significantly correlated with linear growth rate.
Conclusions:
- Dexamethasone's growth-restricting effects may be mediated by suppressing the IGF axis.
- Both dexamethasone dose and regimen are crucial in influencing IGF levels and inducing growth restriction in preterm infants.
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 < or = 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.