From early growth failure to endocrine recovery: Long-term outcomes and GH therapy in SGA and severely preterm children

Soliman, Ashraf T and Ali, Haytham and Ali, Hamdy and Alyafei, Fawzia and Alaaraj, Nada M and Hamed, Noor and Ahmed, Shayma M and Khalil, Ahmed (2025) From early growth failure to endocrine recovery: Long-term outcomes and GH therapy in SGA and severely preterm children. GSC Advanced Research and Reviews, 24 (1). pp. 198-212. ISSN 2582-4597

Background: Children born small for gestational age (SGA) or severely premature (<32 weeks gestation or <1500 g birth weight) are at elevated risk for persistent growth failure and multiple endocrine abnormalities. These include GH–IGF-1 axis dysfunction, insulin resistance, delayed puberty, altered body composition, and neurocognitive impairment. While many catch up by age 2, approximately 10–15% remain short, reflecting partial GH insensitivity. Growth hormone (GH) therapy has emerged as a cornerstone of treatment, though variability in response remains a concern. Objectives: To review the prevalence and clinical impact of endocrine and growth disturbances in children born SGA or severely premature; to evaluate the efficacy and safety of GH therapy; and to identify predictors of therapeutic response and long-term outcomes. Methods: A structured mini-review was conducted using three ESPE abstracts (2025–2026) and 28 peer-reviewed studies published between 2000 and 2025. Included studies addressed GH therapy in SGA or preterm populations and reported outcomes related to height, body composition, metabolic parameters, puberty, bone density, and neurodevelopment. Results were synthesized into six summary tables and four figures, including a forest plot of final height SDS gains. Results: Endocrine abnormalities were highly prevalent: GH–IGF-1 axis dysfunction (60–80%), growth failure (70%), insulin resistance (30–50%), low bone mineral density (40–60%), and delayed puberty (25%). GH therapy significantly improved linear growth (+2.0 to +2.5 SDS), growth velocity (+10 cm/year), and lean body mass (+10–15%), while reducing central adiposity and fracture risk. Weekly GH formulations (somapacitan) matched daily GH in safety and efficacy. Mild, transient insulin resistance was noted in 5–10% of cases. Early treatment (age 2–4 years), low baseline IGF-1, and better nutritional status predicted better outcomes. Neurodevelopmental improvements were suggested but require further study. Conclusion: SGA and severely preterm children who fail to achieve catch-up growth are at high risk for persistent endocrine and metabolic complications. GH therapy offers substantial benefit when started early and tailored to individual risk factors. Long-term follow-up is essential to monitor not only height outcomes but also metabolic health, puberty, and neurocognitive development. Personalized strategies using genotype, weekly GH regimens, and holistic care models are promising next steps in optimizing therapy.