{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:03:53Z","timestamp":1785420233619,"version":"3.56.0"},"reference-count":20,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007831","name":"Capital Health Development","doi-asserted-by":"crossref","award":["2024-1-1131"],"award-info":[{"award-number":["2024-1-1131"]}],"id":[{"id":"10.13039\/100007831","id-type":"DOI","asserted-by":"crossref"}]},{"name":"High-level Public Health Talents Training Plan","award":["AL-02-19"],"award-info":[{"award-number":["AL-02-19"]}]},{"name":"New Quality Foundation of Capital Institute of Pediatrics","award":["XZYC-2025-07"],"award-info":[{"award-number":["XZYC-2025-07"]}]},{"award":["XZYC-2025-07"],"award-info":[{"award-number":["XZYC-2025-07"]}],"id":[{"id":"https:\/\/ror.org\/00zw6et16","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Individual responses to recombinant human growth hormone (rhGH) therapy in children with idiopathic short stature (ISS) vary substantially, limiting pretreatment decision-making. This study aimed to develop and externally validate an interpretable machine learning model for predicting suboptimal 12-month growth response to rhGH therapy. Methods: In this retrospective dual-center study, 901 children from Center 1 were used for model development and internal testing, and 51 children from Center 2 formed an independent external validation cohort. Routinely collected baseline demographic, laboratory, hormonal, radiographic, and family-history variables were used to develop multiple machine learning models. A soft-voting ensemble classifier was constructed and interpreted using SHapley Additive exPlanations (SHAP). The primary outcome was suboptimal growth response, defined as failure to achieve a height gain of at least 0.5 standard deviation score after 12 months of treatment. Results: The optimized ensemble model showed strong discrimination in the internal test set, with an area under the receiver operating characteristic curve of 0.927, and maintained robust performance in the external validation cohort, with an AUC of 0.897. SHAP analysis identified luteinizing hormone, body mass index, TW3 RUS bone age, and insulin-like growth factor 1 as the leading contributors to predicted suboptimal-response risk. Conclusions: An interpretable ensemble machine learning model based on routinely available pretreatment data can predict suboptimal short-term rhGH response in children with ISS and may support individualized risk stratification in pediatric endocrine practice. Clinical trial registration was not required because this was a retrospective analysis.<\/jats:p>","DOI":"10.3390\/diagnostics16142227","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:55:59Z","timestamp":1784249759000},"page":"2227","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interpretable Machine Learning for Predicting Suboptimal 12-Month Growth Response to Recombinant Human Growth Hormone in Children with Idiopathic Short Stature: A Dual-Center External Validation Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Chuanyu","family":"Yang","sequence":"first","affiliation":[{"name":"Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100020, China"},{"name":"Department of Child Health Care, Capital Center for Children\u2019s Health, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifeng","family":"Shao","sequence":"additional","affiliation":[{"name":"Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100020, China"},{"name":"Department of General Surgery, Capital Center for Children\u2019s Health, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100020, China"},{"name":"Department of General Surgery, Capital Center for Children\u2019s Health, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runmin","family":"Zhang","sequence":"additional","affiliation":[{"name":"China United Network Communications Group, Beijing Branch, Beijing 100009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlin","family":"Chen","sequence":"additional","affiliation":[{"name":"Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100020, China"},{"name":"Department of Child Health Care, Capital Center for Children\u2019s Health, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyuan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100020, China"},{"name":"Department of Child Health Care, Capital Center for Children\u2019s Health, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"An","sequence":"additional","affiliation":[{"name":"Department of Child Health Care, Capital Center for Children\u2019s Health, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Peng","sequence":"additional","affiliation":[{"name":"Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100020, China"},{"name":"Department of Child Health Care, Capital Center for Children\u2019s Health, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Child Health Care, Capital Center for Children\u2019s Health, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Child Health Care, Capital Center for Children\u2019s Health, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Child Health Care, Capital Center for Children\u2019s Health, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5536-781X","authenticated-orcid":false,"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100020, China"},{"name":"Department of Child Health Care, Capital Center for Children\u2019s Health, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"ref_1","unstructured":"The Subspecialty Group of Endocrinologic, Hereditary and Metabolic Diseases, the Society of Pediatrics, Chinese Medical Association (2023). 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