Micronutrient deficiencies and metabolic blocks impact pulmonary vasculopathy via the HIF axis and eNOS uncouplingMicronutrient Deficiencies Linked to Pulmonary Hypertension in Children

BackgroundPediatric pulmonary hypertension (PH) is traditionally managed under a strict hemodynamic paradigm, often overlooking systemic metabolic and nutritional drivers. This review introduces the “Cellular Deprivation Model” to evaluate how specific micronutrient deficiencies and metabolic blocks accelerate pulmonary vasculopathy.MethodsA systematic, PRISMA-compliant search was conducted in PubMed/MEDLINE for literature published between January 2000 and April 2026. Keywords intersected pediatric PH with malnutrition, avitaminosis, iron deficiency, and inborn errors of metabolism. Out of 401 unique records, 115 articles were synthesized across clinical and mechanistic tracks.ResultsAcquired deficiencies (including ascorbic acid, thiamine, iron, folate, and cobalamin deficiencies) and inherited disorders of vitamin metabolism (such as Cobalamin C deficiency and folate metabolism disorders) converge on common pathophysiological pathways: the hypoxia-inducible factor (HIF) axis, causing normoxic pseudo-hypoxia, and endothelial nitric oxide synthase (eNOS) uncoupling via tetrahydrobiopterin depletion. In low- and middle-income countries (LMICs), these cellular blocks form a positive socio-hemodynamic feedback loop with congenital heart disease, accelerating vascular media hypertrophy and reducing surgical operability. Strikingly, these nutrition-driven vascular phenotypes demonstrate rapid, complete reversibility upon metabolic rescue.ConclusionStandardized biochemical testing for micronutrients faces severe economic and cold-chain barriers in resource-limited settings. We propose a pragmatic shift toward universal empirical metabolic pre-conditioning—utilizing standardized, low-cost iron, vitamin C, thiamine, and folate regimens—for at-risk pediatric populations. This strategy aims to bypass advanced diagnostic delays, expand surgical operability windows, and mitigate perioperative mortality.