Iron Deficiency as Risk Factor for Adverse Cardiovascular Outcomes in Pediatric Heart Disease: A Systematic Review and Meta-Analysis

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Abstract Background: Iron deficiency (ID) is associated with increased mortality, reduced exercise capacity, and poorer quality of life in adults with heart failure. Although ID is the most common micronutrient deficiency in children, its association with clinical outcomes in individuals under 21 years of age with heart disease remains poorly defined. Objectives: To evaluate the association between iron deficiency and adverse cardiovascular outcomes (ACV)—defined as death, mechanical circulatory support, or heart transplant—and to estimate the prevalence of ID in individuals under 21 years of age with heart disease. Methods: A comprehensive search of PubMed, EMBASE, and Web of Science was conducted until December 2024. Studies including participants under 21 with heart disease assessing ID and ACV were included. Studies were excluded if they reported data from adults or animals, if only abstract data were available, or if they were published in a non-English language. Prevalence was summarized using a weighted mean and 95% confidence interval (CI). The pooled association between ID and ACV was estimated using odds ratios (ORs) with 95% CIs under a random-effects model. Heterogeneity was assessed using Cochran’s Q and I² statistics, and publication bias was explored using funnel plots. Risk of bias was assessed using the ROBINS-E tool. Results: Five retrospective, single-center studies (N=344) were included. ID prevalence ranged from 46.1% to 96.4%, with a weighted mean prevalence of 58.7% (95% CI 53.7–63.7). Three studies reporting ACV outcomes demonstrated that ID was significantly associated with ACV, with a pooled OR of 4.44 (95% CI 2.03–9.71; P<0.001) and low statistical heterogeneity (I²=16.25%). However, the ability to detect heterogeneity was limited by the small number of studies. All included studies demonstrated a high risk of bias, primarily related to selection bias, missing data, and residual confounding. Conclusion: Iron deficiency is highly prevalent among individuals under 21 years of age with heart disease and is associated with an approximately fourfold increase in the risk of adverse cardiovascular outcomes. The substantial risk of bias across studies limits the generalizability of these findings, underscoring the need for well-designed prospective studies to clarify the role of ID in pediatric heart disease.

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