Safety of Gadolinium-based Contrast Agents in Children: A Systematic Review and Meta-Analysis

Background Pediatric safety concerns regarding gadolinium-based contrast agents (GBCAs) used in contrast-enhanced MRI examinations persist. Purpose To conduct a systematic review and meta-analysis to evaluate the safety of GBCAs in children and adolescents undergoing contrast-enhanced MRI examinations, focusing on GBCA-associated adverse drug reaction (ADR), nephrogenic systemic fibrosis (NSF), and gadolinium deposition in the brain. Materials and Methods MEDLINE/PubMed, Embase, Web of Science, and the Cochrane library were searched for articles published up to November 22, 2023. Articles reporting the incidence of GBCA-associated ADRs with information on GBCA type were meta-analytically pooled. The incidence of NSF was systematically reviewed. For gadolinium deposition in the brain, a linear mixed-effects model was used to assess the individual-level association between the dentate nucleus (DN)-to-pons signal intensity (SI) ratios and the number of GBCA administrations, including the interaction effect of GBCA configuration (linear vs macrocyclic). Results Thirty-two studies covering 112 760 examinations for GBCA-associated ADRs, eight studies covering 4895 patients for NSF, and six studies covering 787 examinations for brain gadolinium deposition were included. The acute GBCA-associated ADR rate was 0.25% for physiologic (95% CI: 0.11, 0.53) and 0.13% for allergic-like (95% CI: 0.08, 0.20) reactions. The delayed ADR rate was 0.04% (95% CI: 0.02, 0.07). No patients with NSF were reported (0 of 4895 patients). There was an interaction effect of GBCA category (macrocyclic or linear) on the association between DN-to-pons SI ratios and the number of GBCA administrations (regression coefficient of interaction term, 0.004; 95% CI: 0.002, 0.007; P = .002), with the regression coefficient being 0.0004 for macrocyclic (95% CI: -0.002, 0.003) and 0.004 for linear (95% CI: 0.003, 0.006) agents. Conclusion Adverse reactions to GBCA in children occurred at a low rate, with no patients with NSF reported. The regression coefficient differed between linear and macrocyclic agents when examining their effect on the association between DN-to-pons SI ratios and the number of GBCA administrations. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by McInnes in this issue.