How to address parents’ concerns about MRI contrast agent safety
Hansel J.Otero, M.D., FAAP and AashimBhatia, M.D., M.S., FAAP
Focus on Subspecialties
Gadolinium-based contrast agents (GBCAs) are used in about half of all MRI studies
in children to increase the visualization of normal structures as well as to help
in the diagnosis of pathologies, such as tumors and infection (see figure 1). However,
certain risks exist, and public awareness and parental concern about possible adverse
events related to their use have increased.
Non-dose-related allergic-type reactions occur in about five per 10,000 patients.
Other mild and infrequent adverse reactions include headache, dizziness, nausea and
vomiting. However rare, the occurrence of adverse events makes it mandatory to administer
GBCAs to children only in facilities equipped to manage such reactions and with physicians
The safety of GBCAs became a topic of discussion after research showed the accumulation
of gadolinium in the brain, which was shown to be dose-dependent and cumulative. A
2014 article revealed the initial findings of deposition of GBCAs in the brain (Kanda
T, et al. Radiology. 2014;270:834-841) (see figure 2). Since then, multiple studies have been published
expanding on this phenomenon.
While no known side effects of this gadolinium deposition exist, the Food and Drug
Administration issued a warning in 2015 encouraging patients, families and physicians
to report any symptom that might be related to contrast agents. Since then, we have
learned that not all contrast agents share the same safety profile.
GBCAs are categorized as linear or macrocyclic based on the molecular structure of
the gadolinium chelates that stabilize the molecule and avoid interaction with body
tissues. The current consensus is that linear GBCAs are more likely to deposit within
the brain and other organs than macrocyclic GBCAs, making macrocyclic safer (although
not absolutely safe).
How do we respond to safety concerns?
First, administer gadolinium for MRI exams judiciously and only when necessary. Weigh
potential risks against the benefits, and tailor every patient’s exam accordingly.
For example, recent trends show a decrease in the administration of GBCAs for first-time
headache and seizure patients. Similar initiatives are underway to decrease the use
of contrast in patients expected to need lifelong follow-up such as those with neurofibromatosis
and inflammatory bowel disease.
A 2017 study found that 94% of all pediatric MRI studies are always protocoled by
a pediatric radiologist and that GBCAs are administered judiciously, in agreement
with evidence- and expert-based recommendations (Blumfield E, et al. Pediatr Radiol. 2017;47:665-673).
Second, when contrast is needed, radiology practices should routinely administer the
safest agents and brands available.
A study using data collected at the beginning of 2016 found that 80% of pediatric
hospitals used macrocyclic agents, and 58% had made the switch in 2015-’16 (Mithal
LB, et al. Pediatr Radiol. 2017;47:657-664).
Before gadolinium brain deposition was described, the most feared adverse event related
to GBCA administration was nephrogenic systemic fibrosis (NSF), a scleroderma-like
disease affecting the skin and internal organs and causing progressive fibrosis and
lethal outcomes. However, NSF has been reported in only 23 children, all with pre-existing
chronic kidney disease. Moreover, no cases have been reported since 2012, as it is
avoidable by screening patients at risk of chronic kidney disease and avoiding contrast
in those with estimated glomerular filtration rates under 60 milliliters/minute. Similar
to brain deposition, the safety profile of macrocyclic agents is better and the newest
generation of GBCAs has not been associated with any cases of NSF.
In summary, pediatricians can offer reassurance to parents regarding the judicious
use of gadolinium contrast agents in children and the existence of safer macrocyclic
agents. Pediatricians also should ensure that the imaging facility they recommend
to parents is prepared to manage allergic-type reactions in children.
Finally, as the evidence evolves, families and providers can contact their local radiologist
to address concerns.
Dr. Otero is a member of the AAP Section on Radiology Executive Committee. Dr. Bhatia
is a section member.