What are the long-term sequelae of using Gadolinium (Gadolinium-based contrast agent) as a contrast agent in pediatric patients?

From the Guidelines

Gadolinium-based contrast agents (GBCAs) used in pediatric MRI can potentially cause long-term sequelae, though the risk appears to be low with current practices, and the diagnostic benefits of gadolinium-enhanced MRI typically outweigh the potential risks of gadolinium retention, especially with newer macrocyclic agents. The primary concern is gadolinium deposition in brain tissue and other organs, which has been documented in both adults and children after multiple exposures, particularly with linear GBCAs 1. While no definitive clinical consequences of these deposits have been established in children, caution is warranted. Nephrogenic systemic fibrosis (NSF), a serious condition involving fibrosis of skin and internal organs, is another potential complication but is extremely rare in children with normal renal function.

Key Considerations

• Current recommendations favor using macrocyclic GBCAs (such as gadobutrol, gadoterate meglumine, or gadoteridol) over linear agents in pediatric patients when contrast is necessary, as these have shown less tissue deposition 2, 1.
• The lowest effective dose should be used, and multiple administrations should be limited when possible.
• Special caution should be exercised in very young children, particularly neonates, and in those with impaired renal function.
• In patients with an estimated glomerular filtration rate of <30 ml/min/1.73 m² or on dialysis, administration of gadolinium-containing contrast should be considered individually, and alternative imaging modalities utilized whenever possible 1.

Recommendations for Use

• Macrocyclic or newer linear gadolinium-containing contrast agents should be used in weight-adapted doses.
• If gadolinium-containing contrast agents are necessary, macrocyclic or newer linear gadolinium-containing contrast agents could be administered with patient or parental consent citing an exceedingly low risk (much less than 1%) of developing nephrogenic systemic fibrosis 1.
• Unenhanced T1-weighted and T2-weighted MRI sequences should be considered during follow-up in pediatric patients, especially if good quality enhanced images have been obtained at diagnosis.

From the FDA Drug Label

The consequences of gadolinium retention in the brain have not been established Pathologic and clinical consequences of GBCA administration and retention in skin and other organs have been established in patients with impaired renal function There are rare reports of pathologic skin changes in patients with normal renal function. Adverse events involving multiple organ systems have been reported in patients with normal renal function without an established causal link to gadolinium retention While clinical consequences of gadolinium retention have not been established in patients with normal renal function, certain patients might be at higher risk. These include patients requiring multiple lifetime doses, pregnant and pediatric patients, and patients with inflammatory conditions.

The long-term sequelae of using Gadolinium-based contrast agents in pediatric patients are not established. Pediatric patients may be at higher risk due to gadolinium retention, but the clinical consequences have not been established 3.

From the Research

Long-term Sequelae of Gadolinium-based Contrast Agents in Pediatric Patients

• The long-term effects of using Gadolinium-based contrast agents in pediatric patients are not fully understood, but recent findings have raised concerns about potential toxicity 4, 5, 6.
• Gadolinium deposition in the brain and other organs has been reported, even in patients with normal renal function, which may have unknown clinical effects 5, 6.
• Nephrogenic systemic fibrosis (NSF) is a known risk associated with Gadolinium-based contrast agents, particularly in patients with advanced kidney disease 4, 5, 6.
• The Society for Pediatric Radiology has conducted a survey to evaluate the current status of Gadolinium-based contrast agent usage among pediatric radiologists, which found that these agents are administered judiciously in children, but there is an opportunity to improve their utilization to reduce potential future adverse effects 7.
• Studies have investigated the use of dilute contrast material to decrease the risk of complications, such as contrast-induced nephropathy (CIN) and NSF, and have found that digital flat-panel detectors can enhance image quality during angiography, allowing for the use of more dilute contrast material 8.

Potential Risks and Considerations

• The risk of adverse reactions to Gadolinium-based contrast agents is very low, but the potential for long-term toxicity and unknown clinical effects of gadolinium deposition in the brain and other organs is a concern 4, 5, 6.
• Pediatric radiologists should carefully consider the necessity of Gadolinium-based contrast agent use in children and choose more stable macrocyclic agents as the primary choice 4.
• The American College of Radiology (ACR) Appropriateness Criteria should be followed for various clinical indications, and potential overutilization of Gadolinium-based contrast agents should be avoided 7.