Growth Hormone Therapy in Children Born Small for Gestational Age with Persistent Short Stature: Lessons Learned from Real-World International Databases and Directions for Future Research.

Abstract

Background: Children born small for gestational age (SGA) account for approximately 5% of the newborn population. Although most experience spontaneous catch-up growth during early childhood, up to 10% remain short beyond 2-4 years of age and are classified as having SGA with persistent short stature (SGA-SS). Recombinant human growth hormone (rhGH) has been approved for the treatment of SGA-SS for more than 2 decades, and numerous clinical trials and real-world observational studies have confirmed its efficacy in improving childhood growth and adult height. However, treatment response is highly variable and likely reflects the heterogeneous aetiology of SGA-SS, ranging from intrauterine environmental influences to genetic and epigenetic determinants of growth. Over the past 40 years, large international drug-specific registry programs (KIGS, GeNeSIS, NordiNet IOS, ANSWER, PATRO, NCGS, and ECOS) have provided invaluable data on the long-term safety and efficacy of individual rhGH therapies, including thousands of patients with SGA-SS and extended follow-up.

Summary: Safety outcomes across registries consistently demonstrate a low incidence of serious adverse events, with no excess metabolic or oncological risk compared with background population rates. With the increasing availability of next-generation sequencing, genetic diagnoses can now be identified in a substantial proportion of children with SGA-SS, opening new avenues for stratified treatment approaches.

Key messages: Future research should focus on defining genotype-specific growth responses, optimizing treatment regimens, and integrating next-generation patient databases such as GloBE-Reg to enhance long-term surveillance in the era of conventional and long-acting GH preparations.