GH-IGF-1 axis and rhGH outcomes in children with GHD, ISS and SGA: a systematic review and meta-analysis.
rhGH therapy shows the strongest growth response in children with complete GHD, especially when started early and guided by IGF-1 levels.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
The systematic review and meta-analysis evaluated the GH-IGF-1 axis and rhGH treatment outcomes in 18,642 children with GHD, ISS, and SGA. Baseline IGF-1 SDS was lowest in GHD, and GHD showed greater first-year height velocity and ΔHeight SDS compared to ISS and SGA. Younger age and lower baseline IGF-1 SDS predicted better treatment response.
Abstract
Growth hormone deficiency (GHD), idiopathic short stature (ISS), and persistent short stature after birth small for gestational age (SGA) are major pediatric indications for recombinant human growth hormone (rhGH) therapy, but direct pooled comparisons of GH-IGF-1 axis profiles and treatment outcomes remain limited. We performed a systematic PubMed/MEDLINE search covering January 2005 to December 2024 and identified 47 studies including 18,642 children: 9,214 with GHD, 6,807 with ISS, and 2,621 with SGA. Study quality was assessed using the Newcastle-Ottawa Scale, Cochrane RoB 2.0, and AMSTAR-2. Random-effects meta-analyses were used to calculate pooled mean differences, standardized mean differences, and 95 % confidence intervals. Baseline IGF-1 SDS was lowest in GHD (-2.9 ± 1.1) compared with ISS (-1.5 ± 1.2) and SGA (-1.3 ± 1.1; p<0.001). Complete GHD showed greater first-year height velocity (HV) than ISS (MD +0.80 cm/year; 95 % CI 0.52-1.08) and SGA (MD + 0.62; 95 % CI 0.28-0.96). One-year ΔHeight SDS was also greater in GHD than ISS (SMD +0.24; 95 % CI 0.17-0.31) and SGA (SMD +0.19; 95 % CI 0.09-0.29). ΔIGF-1 SDS and near-adult height gain similarly favored GHD. Younger age at treatment initiation and lower baseline IGF-1 SDS significantly predicted more robust response. Overall, rhGH improves growth and IGF-1 outcomes across GHD, ISS, and SGA, with the strongest response in complete GHD, supporting early treatment and IGF-1-guided therapeutic strategies.
Background
This study addresses the clinical question of how rhGH therapy affects growth outcomes in children with GHD, ISS, and SGA. Prior research has established rhGH as a treatment for these conditions, but direct comparisons of the GH-IGF-1 axis and treatment outcomes across these groups have been limited. Understanding these differences is crucial for optimizing treatment strategies.
Methods
The researchers conducted a systematic review and meta-analysis of 47 studies published between January 2005 and December 2024, involving 18,642 children: 9,214 with GHD, 6,807 with ISS, and 2,621 with SGA. Study quality was assessed using the Newcastle-Ottawa Scale, Cochrane RoB 2.0, and AMSTAR-2. Random-effects meta-analyses were used to calculate pooled mean differences, standardized mean differences, and 95% confidence intervals.
Results
Baseline IGF-1 SDS was significantly lower in children with GHD compared to those with ISS and SGA. Complete GHD showed a greater first-year height velocity compared to ISS and SGA, with mean differences of +0.80 cm/year and +0.62 cm/year, respectively. The one-year ΔHeight SDS was also greater in GHD compared to ISS and SGA. Younger age at treatment initiation and lower baseline IGF-1 SDS were associated with a more robust response to rhGH therapy.
Interpretation
The findings suggest that rhGH therapy is most effective in children with complete GHD, particularly when initiated at a younger age and with lower baseline IGF-1 SDS. While the effect sizes are statistically significant, the clinical significance may vary depending on individual patient factors. The study's reliance on pooled data introduces potential heterogeneity, and the results are specific to pediatric populations.
Key findings
- Baseline IGF-1 SDS was lowest in GHD (-2.9 ± 1.1) compared with ISS (-1.5 ± 1.2) and SGA (-1.3 ± 1.1; p<0.001).
- Complete GHD showed greater first-year height velocity than ISS (MD +0.80 cm/year; 95% CI 0.52-1.08) and SGA (MD +0.62; 95% CI 0.28-0.96).
- One-year ΔHeight SDS was greater in GHD than ISS (SMD +0.24; 95% CI 0.17-0.31) and SGA (SMD +0.19; 95% CI 0.09-0.29).
- ΔIGF-1 SDS and near-adult height gain similarly favored GHD.
- Younger age at treatment initiation and lower baseline IGF-1 SDS significantly predicted more robust response.
Limitations
- Pooled data from multiple studies may introduce heterogeneity.
- Findings are limited to pediatric populations.
- Study quality varies across included studies.
- Potential for publication bias in selected studies.