Effectiveness of Recombinant Human Growth Hormone Therapy in Small‐for‐Gestational‐Age Children With Short Stature: A Stratified Analysis Based on Genetic Variant Status
Sanghee Park, Yena Lee, Hwal Rim Jeong, Eun Young Kim, Eu‐seon Noh, Hye young Jin, Eun Byul Kwon, Hye Jin Lee, Young‐Jun Seo, Young Suk Shim, Su Jin Kim, Ji‐Eun Lee, Nan Young Kim, Sangkyoon Hong, Min Jae Kang, Il Tae HwangABSTRACT
Objective
This study aimed to evaluate the impact of pathogenic genetic variants on growth outcomes following 3 years of recombinant human growth hormone (rhGH) therapy in children born small for gestational age with persistent short stature (SGA‐SS).
Design
A retrospective cohort study.
Patients
One hundred and seventy‐nine SGA‐SS children who underwent clinical and genetic evaluation were classified into variant‐positive ( n = 30) and variant‐negative groups ( n = 149).
Measurements
Clinical characteristics and growth outcomes were assessed over 3 years of rhGH therapy.
Results
At baseline, the variant‐positive group had significantly lower height standard deviation score (SDS) (−2.83 vs. −2.28, p < 0.001) and higher rates of intellectual disability (36.7% vs. 7.4%, p < 0.001) and congenital anomalies (30.0% vs. 6.7%, p < 0.001). rhGH therapy promoted longitudinal growth in both groups (evaluated n = 142); after 3 years, the estimated marginal mean (EMM) of height SDS reached −1.30 ± 0.10 in the variant‐positive group and −0.93 ± 0.04 in the variant‐negative group. However, linear mixed model analysis revealed a progressive attenuation of incremental height SDS gain in the variant‐positive group as the treatment progressed, with significant interaction estimates observed at Year 1 (Estimate −0.18), Year 2 (Estimate −0.31) and Year 3 (Estimate −0.36; all p < 0.05).
Conclusion
As one of the first longitudinal analyses utilizing repeated‐measures modelling in a genetically characterized patient population, this study demonstrates that while rhGH therapy effectively promoted linear growth in SGA‐SS children, patients with a molecular diagnosis presented with lower baseline stature and an attenuated incremental growth response over time, highlighting the importance of genetic evaluation for personalized treatment strategies.