Growth hormone therapy in high-risk pediatric populations: Integrated growth, metabolic, and safety outcomes in SGA, preterm, and Russell–silver syndrome

Background: Growth hormone (GH) therapy is widely used to enhance growth outcomes in children with growth disorders, including those born small for gestational age (SGA), preterm infants, and individuals with Russell-Silver Syndrome (RSS). While GH therapy demonstrates consistent efficacy in improving height and metabolic parameters, variability in response and concerns about long-term safety require careful evaluation.

Objective: This review aims to assess the effects of GH therapy on growth outcomes, metabolic health, and safety profiles in children born SGA, preterm, and those diagnosed with RSS, and to provide updated clinical recommendations for optimizing treatment strategies.

Methods: A systematic review of 95 clinical studies published between 2000 and 2025 was conducted, analyzing outcomes in over 6,500 pediatric patients receiving GH therapy. Data were synthesized from randomized controlled trials, cohort studies, and observational research, focusing on changes in height standard deviation scores (SDS), growth velocity, IGF-1 levels, and metabolic safety outcomes.

Results: In SGA children, GH therapy resulted in a mean height SDS improvement of +2.2 and a 36% increase in growth velocity, with the most favorable outcomes when treatment was initiated before 4 years of age. Mild insulin resistance and glucose intolerance were noted in a subset of patients. Preterm infants demonstrated an average height SDS gain of +1.9 and a 32% increase in growth velocity, particularly when GH therapy was combined with optimal nutritional strategies. Transient insulin resistance was occasionally observed but without significant long-term consequences. In RSS patients, GH therapy improved height SDS by +1.8 and growth velocity by 27%, although responses varied depending on the underlying genetic etiology. Metabolic benefits included improvements in IGF-1 levels and body composition, with minimal adverse effects. Weekly GH regimens were found to be comparable to daily injections in efficacy and safety across all populations.

Conclusion: GH therapy significantly improves growth outcomes and metabolic profiles in children born SGA, preterm, and with RSS. Early initiation and individualized treatment approaches optimize height gains while minimizing metabolic risks. Although generally safe, GH therapy requires regular monitoring of glucose metabolism and metabolic parameters, particularly in SGA and preterm populations. Personalized protocols based on genetic and nutritional factors, along with long-term follow-up, are essential to maximizing the therapeutic benefits while ensuring safety. Future research should further explore genetic predictors of GH response and the long-term metabolic and cardiovascular outcomes of GH-treated children.