Longitudinal Hemoglobin Trajectories and Their Association with Growth Response in Short Stature Children (Aged <15 Years) Undergoing Weekly Growth Hormone Therapy: A Real-World Cohort Study

Qingbo Xu,1,2 Yu Yang,1,2 Liling Xie,1,2 Dongguang Zhang,1,2 Haiying Zou,1,2 LanFang Cao,1,2 Li Yang1,2 1Department of Endocrinology, Genetics and Metabolism, Jiangxi Provincial Children’s Hospital, Nanchang, Jiangxi, 330038, People’s Republic of China; 2Department of Endocrinology, The Affiliated Children’s Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330038, People’s Republic of ChinaCorrespondence: Li Yang, Email [email protected]: Growth hormone (GH) therapy affects linear growth and may influence hematopoiesis, but dynamic hemoglobin (Hb) changes in children remain unclear.Objective: To characterize longitudinal Hb trajectories during weekly GH treatment in short stature, including idiopathic short stature (ISS) and growth hormone deficiency (GHD), and to assess their associations with growth response.Methods: This retrospective cohort study included 165 children with short stature who received once-weekly PEGylated GH therapy for at least 12 months. Hematologic/growth-related parameters were collected at baseline, 6 and 12 months. Group-based trajectory modeling (GBTM) identified Hb trajectory groups. Spearman correlation analysis was performed to evaluate the association between Hb, red blood cell (RBC) count, and insulin-like growth factor 1 (IGF-1). Multivariate logistic regression was used to identify predictors of Hb improvement (≥ 5 g/L).Results: Three distinct Hb trajectory groups were identified: ascending (n = 82), ascending-then-descending (n = 51), and stable (n = 32). The ascending group demonstrated the most favorable height SDS improvement at 12 months (mean ΔHtSDS = 1.01), while the ascending-then-descending and stable groups showed more modest gains. IGF-1 levels were moderately correlated with Hb at 12 months (ρ = 0.308, p = 0.001) and RBC counts (ρ = 0.236, p = 0.014). Logistic regression revealed no independent baseline predictor of Hb improvement; however, the inclusion of Hb trajectory group significantly enhanced the predictive model for growth response (adjusted R² increased from 0.129 to 0.240; p = 0.018).Conclusion: Hb trajectories vary significantly among children receiving GH therapy and are moderately associated with height outcomes. Longitudinal monitoring of Hb may serve as a cost-effective dynamic biomarker to guide personalized GH dose titration in pediatric growth disorders. If validated, Hb monitoring may serve as a practical biomarker for personalized GH dosing in pediatric growth disorders. Keywords: trajectory analysis, growth hormone therapy, hemoglobin trajectory, pediatric endocrinology