| Objective: The final height gain in children with short stature treated with genetic recombinant human growth hormone(rhGH)therapy mainly depends on the efficacy of rhGH during the first year.This study aimed to investigate the risk factors of rhGH efficacy in the first year and to develop and validate a clinical predictive model for poor therapeutic response during the first year of rhGH treatment.Methods:1.Analysis of risk factors of rhGH efficacy: Children who were diagnosed and treated with rhGH for at least 1 year at the Department of Pediatrics,the First Affiliated Hospital of China Medical University,due to short stature from January 2008 to January 2022 were selected for the study.The baseline data of the children at the initiation of rhGH treatment and the clinical outcomes after 1 year of rhGH treatment were collected. Univariate linear regression analysis to enquire factors related to the efficacy of rhGH year 1.Multivariate linear regression analysis was used to analyze the independent risk factors affecting the efficacy of rhGH.2.Development and validation of clinical predictive model: 627 children with growth disorders(GHD,SGA,ISS,TS)from the long term growth study cohort(LGS)were retrospectively evaluated.Poor response to rhGH treatment was defined as a height gain< 0.4 SDS at the 1st year of rhGH treatment.Restricted cubic splines(RCS)were used to investigate the risk association of predictors with poor response to rhGH treatment.The study cohort was split into training and test sets in a 6:4 ratio.In the training set,the most valuable predictor variables were screened by LASSO(least absolute shrinkage and selection operator)regression analysis and a multivariate logistic regression model was constructed.Receiver operating characteristic(ROC)curves,calibration curves,decision curve analysis(DCA),and clinical impact curves(CIC)were used to assess the predictive model’s accuracy and clinical value.The predictive accuracy of the model was validated on the testing set.Results:1.Analysis of risk factors of rhGH efficacy: 83 children with short stature were enrolled.The risk factors significantly associated with rhGH efficacy included age at rhGH initiation(β=-0.11,95%CL-0.21 to-0.01,P=0.025),bone age(β=-0.23,95%CL-0.38 to-0.07,P=0.005),etiological diagnosis of short stature(β=1.3,95%CL 0.09 to 2.6,P=0.036).The results of multivariate linear regression analysis showed that the age of rhGH treatment initiation(β=-0.11,95%CI-0.21 to 0.02,P=0.020)and the etiological diagnosis of short stature(β=1.4,95%CI 0.15 to 2.6,P=0.028)were independent risk factors affecting the short-term efficacy of rhGH treatment.2.Development and validation of clinical predictive model: Two predictive models containing 8 baseline predictors(diagnosis,age,height SDS,bone age minus chronological age,rhGH dosage,distance from mid-parental height in SDS,weight SDS,IGF-1 SDS)and 1 post-treatment predictor(height SDS gain at 6 months)were constructed by multivariate logistic regression analyses.The nomogram was built based on the multivariate predictive model and showed good discrimination and model fit effects in both the training set and the testing set.DCA and CIC analyses presented good clinical usability.Conclusion:1.Analysis of risk factors of rhGH efficacy: The independent risk factors affecting the efficacy of rhGH treatment in children with growth disorders include the age of rhGH treatment initiation and the etiological diagnosis of short stature.2.Development and validation of clinical predictive model: The clinical predictive model for predicting the probability of poor short-term response of rhGH treatment in pediatric patients with growth disorders(Model A and Model B)is useful and can assist physicians in making clinical decisions. |
PDF Full Text Request