On March 30, 2022, the FDA issued a Drug Safety Communication (DSC) recommending thyroid testing within three weeks for all infants and children under three years of age who receive iodinated contrast media (ICM). This communication followed approval of a change in labeling for ICM, adding a warning and precaution about thyroid dysfunction and listing thyroid dysfunction as an adverse reaction. 

Evidence supporting a significant risk of clinically detrimental hypothyroidism in newborns and children through 3 years after exposure to ICM does not bear scrutiny. In coming to its conclusion, the FDA cited eleven research studies published between 1987-2020. The study designs and conclusions from the reports forming the basis of the FDA DSC are widely variable. Most had small patient numbers, few included control groups, and additional sources of iodine exposure (e.g., topical application) were not accounted for. Not included in the cited literature are additional published studies, including a retrospective study using a control cohort and a prospective randomized controlled study involving preterm infants – neither of which found statistical differences in thyroid function between exposed and control cohorts. The members of the Pediatric Endocrine Society (PES) are experts in pediatric hypothyroidism, and their position statement on the FDA DSC states that "there [is] no data to support the potential negative impact of a single episode of transient, ICM-induced hypothyroidism ." As a whole, it is unclear if the FDA's referenced reports are generalizable to the entire pediatric population less than three years of age to support the overall recommendations of the FDA DSC at this time.

Implementation of the current DSC recommendations has far-reaching consequences. ICM is routinely used across many pediatric subspecialties, including interventional radiology, diagnostic radiology, pediatric surgery, and pediatric cardiology. Nearly half of cardiac catheterization procedures are performed in children less than three years of age. The burden of pre-procedural thyroid screening and post-exposure surveillance for patients and providers has not been assessed and would require significant resources and coordination. Since no evidence-based threshold values are established to guide the initiation of thyroid hormone replacement therapy in children under three years of age, interpretation of results to inform follow-up or treatment decisions is not straightforward. Further, many patients receiving injectable ICM may be at independent risk for late neurodevelopmental issues based on their underlying primary disease processes, particularly those with prematurity, prolonged hospitalization, and congenital heart disease. Fundamentally, there is no clear consensus as to how to distinguish, treat, and evaluate any potential detrimental long-term effects of transient ICM-induced hypothyroidism in these patient populations. Future carefully designed long-term studies will be necessary to discriminate if any additional independent risk exists due to ICM exposure. 

SCAI believes the current data are insufficient to warrant the course of action described within the recent FDA DSC. The DSC recommends monitoring for the possibility of impaired thyroid function, even though these effects are uncommon and generally transient. To date, no independent causal link has been established in any study between ICM exposure and the long-term effects of extended hypothyroidism, such as motor, hearing, or neurocognitive disabilities. Prevention of future potential complications will require well-designed research to define the actual risk of ICM exposure and to formulate an appropriate monitoring regimen for at-risk populations.

As medical professionals entrusted with caring for infants and children, we support evidence-based patient management strategies for the utmost safety of our most vulnerable young patients. ICM use is critical for the diagnostic and therapeutic treatment of infants and children with congenital heart disease. As with other medications, there is awareness within the pediatric cardiology community that ICM use should be minimized to achieve adequate imaging and procedural success. SCAI supports well-designed prospective multicenter studies to define at-risk groups accurately, clarify the risks of ICM exposure, and provide rational monitoring and treatment guidelines. Establishing consensus with manufacturers, healthcare providers, and the FDA in defining significant risk is necessary to understand the impact of ICM on this patient population. SCAI looks forward to collaborating with all key stakeholders to create appropriate recommendations for patient safety and clinical practice.