Recombinant human growth hormone for children born small for gestational age: meta-analysis confirms the consistent dose-effect relationship on catch-up growth.

BACKGROUND: The optimal treatment regimen of recombinant human GH (r-hGH) for short children born small for gestational age (SGA) is still under discussion. METHODS: A meta-analysis was performed of existing clinical trials that investigated the treatment of r-hGH in short children diagnosed SGA or with intrauterine growth retardation to determine the relationship between the daily r-hGH dose (placebo/no treatment; 0.033 mg/kg/day; 0.067 mg/kg/day) and the effect on growth [change in height-SD score (SDS) for chronological age]. A mathematical model describing the dose-response relationship was produced, and growth response (gain in height-SDS) to 2 yr of r-hGH 0.033 mg/kg/day [somatropin (rDNA origin) for injection; Serono] was estimated and compared with the response to other r-hGH formulations. RESULTS: The relationship between r-hGH dose and 2-yr growth response was described by an equation. The equation yielded a mean difference in height- SDS gain of 0.48 (0.35) between r-hGH 0.033 and 0.067 mg/kg/day in favor of the higher dose. The height-SDS gain after 2 yr of Serono r-hGH formulation, 0.033 mg/kg/day was estimated as 1.2. Comparison of this estimate to the growth response to 2-yr treatment at 0.033 mg/kg/day of other r-hGH formulations (mean difference in height-SDS 0.05, lower limit of the 95% confidence interval=-0.15) confirmed that growth response to Serono r-hGH formulation 0.033 mg/kg/day is an inferred response estimated to be within the range of observed responses to a (non-Serono formulation) r-hGH dose of 0.033 mg/kg/day. CONCLUSION: There is a clear dose-response relationship for r-hGH in the treatment of short children born SGA and the analysis confirmed that treatment with Serono r-hGH formulation 0.033 mg/kg/day should provide a meaningful therapeutic response.