Growth hormone therapy for children born small for gestational age: height gain is less dose dependent over the long term than over the short term.
BACKGROUND
Approximately 3% of children are born small for gestational age (SGA), and approximately 10% of SGA children maintain a small body size throughout childhood and often into adult life. Among short SGA children, growth hormone (GH) therapy increases short-term growth in a dose-dependent manner; experience with long-term therapy is limited.


OBJECTIVE
To delineate the dose dependency of long-term height gain among short SGA children receiving GH therapy.


METHODS
We performed an epianalysis of the first adult height data for SGA children (n = 28) enrolled in 3 randomized trials comparing the growth-promoting efficacy of 2 continuous GH regimens (33 or 67 microg/kg per day for approximately 10 years, starting at approximately 5 years of age); in addition, we performed a meta-analysis of the adult height results published previously and those presented here.


RESULTS
Epianalysis outcomes (n = 28) suggested that adult height increased more with a higher-dose regimen than with a lower-dose regimen. In the meta-analysis (n = 82), the higher-dose regimen was found to elicit a long-term height gain superior to that achieved with the lower-dose regimen by a mean of 0.4 SD (approximately 1 inch). Children who were shorter at the start of therapy experienced more long-term height gain.


CONCLUSIONS
These findings confirm GH therapy as an effective and safe approach to reduce the adult height deficit that short SGA children otherwise face. In addition, the first meta-analysis indicated that height gain is less dose dependent over the long term than over the short term, at least within the dose range explored to date. For SGA children whose stature is not extremely short, current data support the use of a GH dose of approximately 33 microg/kg per day from start to adult height, particularly if treatment starts at a young age; shorter children (for example, height below -3 SD) might benefit from an approach in which short-term catch-up growth is achieved with a higher dose (> or =50 microg/kg per day) and long-term growth to adult height is ensured with a GH dose of approximately 33 mug/kg per day. Because GH-induced accelerations of height and weight gain evolve in parallel, the dose tapering from > or =50 microg/kg to approximately 33 microg/kg can be accomplished by simply maintaining the absolute GH dose (in micrograms) while the child gains weight (in kilograms). With this algorithm, more growth-responsive children taper their GH dose down to approximately 33 microg/kg per day more quickly.
de Zegher
Francis
F
University of Leuven, Leuven, Belgium. francis.dezegher@uz.kuleuven.ac.be
Hokken-Koelega
Anita
A
D000328:Adult; D000704:Analysis of Variance; D001827:Body Height / Q000187:drug effects*; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006128:Growth / Q000187:drug effects; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000254:growth & development*; D008297:Male
D019382:Human Growth Hormone