GH–IGF-1 axis and rhGH outcomes in children with GHD, ISS and SGA: a systematic review and meta-analysis

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.