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

Abstract

Background: Iron deficiency (ID) increases mortality, reduces exercise capacity, and worsens quality of life in adults with heart failure. ID is the most common micronutrient deficiency in children; however, its association with clinical outcomes in individuals under 21 with heart disease remains unclear.

Objectives: Assess the association between ID and adverse cardiovascular outcomes (ACV) defined as death, mechanical circulatory support, or heart transplant, and estimate ID prevalence in individuals under 21 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. Prevalence was summarized using a weighted mean and 95% confidence interval (CI). The pooled effect was estimated using odds ratio (OR) and 95% CI via a random-effects model. Heterogeneity was assessed with Cochran's Q and I² statistics, and publication bias via funnel plots. Risk of bias was assessed using the ROBINS-E tool.

Results: Five retrospective studies (N=344) were included. The prevalence of ID ranged from 46.1% to 96.4%, with a weighted average of 58.7% (95% CI 53.7, 63.7). Three studies with ACV data showed ID was significantly associated with ACV (OR 4.44, 95% CI 2.03-9.71, P<0.001) with low heterogeneity (I²=16.25%). Studies had high risk of bias due to selection bias, missing data, and confounder bias.

Conclusion: ID is common in individuals under 21 with heart disease and increases ACV risk fourfold. High risk of bias limits generalizability, highlighting the need for robust studies.

This review was registered with PROSPERO (CRD42024543116).