[Etiological and clinical classification of pulmonary hypertension in children]

Objective: To investigate the etiological and across clinical classification features in children with pulmonary hypertension (PH). Methods: Case series study. This case series included 269 children with PH who were admitted to Department No. 2 of Respiratory Medicine, Beijing Children's Hospital, Capital Medical University, from January 2017 to December 2024. Demographic characteristics, clinical manifestations, and etiological evaluation results were collected. According to the etiology, PH was classified into pulmonary arterial hypertension (PAH), PH associated with left heart disease, PH associated with lung diseases and (or) hypoxia, chronic thromboembolic pulmonary hypertension (CTEPH), and PH with unclear and (or) multifactorial mechanisms, and others. Results: Among 269 patients with PH, 153 were boys and 116 were girls. The age of onset was 8.0 (3.2, 28.0) months, and 151 patients (56.1%) developed PH before one year of age. The cohort included 157 patients (58.4%) with PAH, 5 patients (1.9%) with PH associated with left heart disease, 63 patients (23.4%) with PH associated with lung diseases and (or) hypoxia, and 21 patients (7.8%) with PH of unclear and (or) multifactorial mechanisms. No cases of CTEPH were identified. The remaining 23 patients (8.6%) required supplementary etiological annotation, including immune-inflammatory-related PH in 9 patients (3.3%) and PH associated with genetic syndromes or chromosomal abnormalities in 14 patients (5.2%). Among 43 patients with heritable or idiopathic PAH, pathogenic or likely pathogenic genetic variants were identified in 27 patients (62.8%), involving 12 PAH-associated genes. Variants in BMPR2 gene and TBX4 gene were identified in 6 and 5 patients, respectively. Twenty-one patients (7.8%) had overlapping etiologies involving 2 or more potential contributing mechanisms. Conclusions: In this pediatric PH cohort, PAH and PH associated with lung diseases and (or) hypoxia represented the major etiological categories. Some patients had underlying genetic factors, immune-inflammatory conditions, genetic syndromes, or chromosomal abnormalities, and overlapping etiologies were observed.